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Metal Salen Complexes in Anion Binding and Catalysis

Permanent Link: http://ufdc.ufl.edu/UFE0021404/00001

Material Information

Title: Metal Salen Complexes in Anion Binding and Catalysis
Physical Description: 1 online resource (140 p.)
Language: english
Creator: Libra, Eric Ryan
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2007

Subjects

Subjects / Keywords: Chemistry -- Dissertations, Academic -- UF
Genre: Chemistry thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Most forms of life require the recognition and transportation of anions. There have been numerous efforts to develop synthetic receptor systems that are both efficient and selective for the coordination of anions. Nature often employs the use of OH groups for anion coordination, yet this binding mode is one that has not been explored in the area of synthetic anion receptor design. A series of substituted metal salen compounds have been developed that show a high affinity for the coordination of anions. The rigid metal salen macrocycle can orientate four phenol groups into a tetrahedral array that tightly and selectively binds fluoride through four strong OH-F hydrogen bonding interactions. The size of the anion binding cavity can be regulated by the incorporation of different metal centers, enabling the properties of the system to be modified. Metals also offer convenient pathways to report the binding event via spectral changes from the strong metal to ligand charge transfer transitions, making these receptors anion sensors. Not only can the metal salen system organize groups for anion binding, they can also be used as chiral catalysts. The synthesis of a rigid and sterically bulky metal salen complex has been undertaken for the use as an asymmetric catalyst to promote organic transformations.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by Eric Ryan Libra.
Thesis: Thesis (Ph.D.)--University of Florida, 2007.
Local: Adviser: Scott, Michael J.

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2007
System ID: UFE0021404:00001

Permanent Link: http://ufdc.ufl.edu/UFE0021404/00001

Material Information

Title: Metal Salen Complexes in Anion Binding and Catalysis
Physical Description: 1 online resource (140 p.)
Language: english
Creator: Libra, Eric Ryan
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2007

Subjects

Subjects / Keywords: Chemistry -- Dissertations, Academic -- UF
Genre: Chemistry thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Most forms of life require the recognition and transportation of anions. There have been numerous efforts to develop synthetic receptor systems that are both efficient and selective for the coordination of anions. Nature often employs the use of OH groups for anion coordination, yet this binding mode is one that has not been explored in the area of synthetic anion receptor design. A series of substituted metal salen compounds have been developed that show a high affinity for the coordination of anions. The rigid metal salen macrocycle can orientate four phenol groups into a tetrahedral array that tightly and selectively binds fluoride through four strong OH-F hydrogen bonding interactions. The size of the anion binding cavity can be regulated by the incorporation of different metal centers, enabling the properties of the system to be modified. Metals also offer convenient pathways to report the binding event via spectral changes from the strong metal to ligand charge transfer transitions, making these receptors anion sensors. Not only can the metal salen system organize groups for anion binding, they can also be used as chiral catalysts. The synthesis of a rigid and sterically bulky metal salen complex has been undertaken for the use as an asymmetric catalyst to promote organic transformations.
General Note: In the series University of Florida Digital Collections.
General Note: Includes vita.
Bibliography: Includes bibliographical references.
Source of Description: Description based on online resource; title from PDF title page.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility: by Eric Ryan Libra.
Thesis: Thesis (Ph.D.)--University of Florida, 2007.
Local: Adviser: Scott, Michael J.

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2007
System ID: UFE0021404:00001


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98176056d63250f2c799b3572bb97c7fb0be6710







METAL SALEN COMPLEXES IN ANION BINDING AND CATALYSIS


By

ERIC R. LIBRA


















A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

UNIVERSITY OF FLORIDA

2007


























2007 Eric R. Libra




































To Caroline and my parents and my entire family









ACKNOWLEDGMENTS

Although I am unaware of when I made the decision to become a chemist, I know my

interest in science and discovery has been in place since an early age. As a young child I always

had an interest in dinosaurs and astronomy, but the person who may just have steered me in the

direction of chemistry was Mr. Wizard. Watching his program led me to want to perform

experiments at home and also stoked my desire for my first chemistry set. There are many

people who have helped me reach this point not only as a chemist but also as a person and I

would like to thank them for all they have done.

I owe a dept of gratitude to my parents, Dennis and JoAnne Libra, who have been

instrumental in my life. I would not be in the position I am in now if it was not for them. They

always put their children and our educations first and whether it was driving us to soccer practice

or piano lessons or making the financial sacrifices so that my brothers and I could attend the

colleges of our choosing, they have been selfless through it all. I thank my younger brothers,

Broc and Garrett, for the fun times growing up and for taking all the abuse a big brother dishes

out, as well as not giving it back to me too much when you both outgrew me and I was the

"little" brother. I thank my grandparents, John and Bertha Kowalczyk, who help raise me as

well as my grandparents, Peter and Cecelia Libra for the Sunday afternoon spaghetti dinners.

Three professors have had a tremendous impact on my life and have guided me to where I

am today. Dr. William Armstrong at Boston College was the first professor to give me the

opportunity to work in a research environment, and this positive experience is what made me

decide to attend graduate school. He was also instrumental in helping me pick a graduate school

and I eventually realized that the University of Florida and the Scott Group was the place where I

belonged. My two plus years working in the X-Ray lab at the University of Florida, were very

rewarding and I have Dr. Khalil Abboud to thank for that. Khalil was always there to talk and to









give advice on chemistry and many other subjects. I thoroughly enjoyed my time working with

him and it was nice to have a few hours a day to be able to concentrate on topics other than

synthesis. Most importantly, I would like to thank my advisor Dr. Michael Scott. Mike was

responsible for my being at UF, and I hope that I have proven that his decision to bring me here

was the right one. Since my arrival in Gainesville he has been a great mentor and I think that my

chemical knowledge and intuition has exponentially increased since my arrival. He always was

able to make a helpful suggestion when I hit a wall, and I was always ecstatic when it worked.

He is one of the rare professors that has found the perfect median between giving the students

enough space to figure things out for themselves, yet involved enough so students have a

direction and a goal.

Many other people made my time here more enjoyable. I would like to thank my lab

mates Ivanna, Hue, Nella, Ranjan, Ozge, Candace, Melanie, Patrick, Nate, Gary, Nicolas,

Dempsy and Anna, among many other short term visitors, from whom I have learned many

practical aspects of chemistry including many tricks of the trade. I had the pleasure of working

with a great undergraduate, Nate Strutt, and I hope I did not teach him too many bad habits these

last two years. A special thanks goes out to my lab mate Candace and pseudo lab mate Justin for

making inorganic chemistry fun, from classes, to cumes, to orals, to the years of research. They

were always there together to talk sports or get a drink at Gator City to take out minds off the

tasks at hand. I am sure my graduate experience would not have been as enjoyable without

them. Another thanks goes to James and the entire Quarter Barrel Saturday crew. It was

definitely the most enjoyable part of my last four years in Gainesville and even if it was only a

few Saturday afternoons a year it was much needed in order to maintain our sanity.









Most importantly, I would like to thank my wife to be Caroline. I moved to Gainesville

with many mixed feelings, as I knew it would be several years we would not be together. Being

apart for so long has been tremendously difficult and I can not wait to be back together and share

our lives once again. I could not have done this without her love, encouragement and especially

her patience with me and our situation.









TABLE OF CONTENTS

page

A CK N O W LED G M EN T S ................................................................. ........... ............. .....

L IS T O F T A B L E S .........................................................................................10

L IST O F FIG U R E S .................................... .. .... .............. .................. ............... 11

ABSTRAC T ............................... ..................... 15

CHAPTER

1 INTRODUCTION ............... ................. ........... .............................. 16

A union C coordination M odes ............................................................................ .................. 17
Initial Studies of Anion Receptor System s.................................... .......................... ......... 18
Pyrrolic M acrocycle Receptors................... ............ ............ .... ...... ............... 19
Biologically Relevant Receptors Incorporating the Guanidinium Group ...........................20
N eutrally C charged R eceptors................................................. ...................... ............... 20
Anion Coordination Through Lewis Acidic Metals .................................... ............... 21
Hydrogen Bonding Interactions Through Oxygen Donors ......................................... 22
Research Objectives.......... ..................... ........ ... .... ............ 23

2 METAL SALEN COMPLEXES INCORPORATING TRIPHENOXYMETHANES:
EFFICIENT, SIZE SELECTIVE BINDING OF FLUORIDE WITH A VISUAL
R E P O R T ................... ...................2...................8..........

In tro d u ctio n ................... ...................2...................8..........
R results and D discussion ............. ............. ........................................... ..... ...... 28
A advantages of the Salen M acrocycle ................................. ...........................................29
D design of R eceptor System ................................................................. ........ ..............29
A union B finding P properties ................................................................. ......................3 1
Binding Constants ................................................... 33
Solid State Structure of [2-2-F] ....................................................................... 34
A nion B finding Studies for 2-3 ............................................................. .....................34
C onclu sions.......... ..........................................................35
Experim ental M ethods................................................. 36
G general C considerations ......................................................................... .. ................ .. 36
Synthesis of 2-1 ................................................... ............... .. ...... 36
Synthesis ofR,R-2-1 ......................... ....... ........ .. ........ ......... 37
Synthesis of R,R-2-2 .................. ..................................... ................. 37
Synthesis of 2-2 ............................................................ .................. 38
Synthesis of 2-3 ............................................................ .................. 38
Synthesis of [2-2-F ](B u4N ) ................................................................... ....................39
Determination of binding constants (LogKs) ............ ............................................39









3 A SYNTHETIC MODEL OF THE CLC CHLORIDE ION CHANNEL; A
STRUCTURAL AND ANION BINDING STUDY ...........................................................52

In tro du ctio n ................... ...................5...................2..........
Results and Discussion ...................................... .. ......... ....... ..... 53
Salens as A union R eceptors ..................................................................... ...................53
Synthesis of a M ixed Salen R eceptor.................................... .......................... .......... 54
Anion Coordination and Binding Constants......................................... ............... 56
Solid State Structure .................. ..................................... ................. 57
C onclu sions.......... ..........................................................57
Experimental Methods ............................................ ................... 58
General Considerations. ............................ ...... ....... .... ..... ............... 58
Determination of binding constants (LogKs)........................................................58
Synthesis of 3-1 ................................................................................................. .... 58
Synthesis of 3-2 ................................................................... 59
S y n th e sis 3 -3 ............................................................................................................. 6 0
Synthesis of 3-4 .......................................................................................................6 1
S y n th e sis o f 3 -5 ............................................................................................................... 6 1
S y n th e sis o f 3 -6 ............................................................................................................... 6 2
S y n th e sis o f 3 -7 ............................................................................................................... 6 3
S y n th e sis o f 3 -8 ............................................................................................................... 6 3

4 METAL SALEN UREA COMPLEXES AND THEIR HIGH AFFINITIES FOR THE
H A L ID E S ..........................................................................6 9

Introduction ......... .............. ...............................69
R e su lts an d D iscu ssio n ..................................................................................................... 7 0
C onclu sions.......... ..........................................................79
Experim ental M ethods................................................. 80
G en eral C on sid eration s ............................................................................................. 80
Synthesis of 4-2 ...................................... ...... ......81
Synthesis of 4-3 ............................................................ .................. 8 1
Synthesis of 4-6 ............................................................ .................. 82
Synthesis of 4-7 ............................................................ .................. 82
Synthesis of 4-8 ............................................................ .................. 82

5 DESIGNER LEWIS ACIDS; THE DEVELOPMENT OF EXTREMELY BULKY AND
RIGID DINUCLEAR CHIRAL CATALYSTS ........................................99

In tro d u ctio n ............. ..... ................. ...............................................................9 9
Jacobsen's C atalyst................................................... 99
Lewis Acid Catalysts ................................. ........................... ............100
Z n Salens in C analysis ......................... ....... ........ ................100
The Promotion of the Diels-Alder Reaction by a Lewis Acid .................................... 102
General Approaches of Synthetic Design........................................................... 102
Results and Discussion .............. ......... ............................. ....... 102
B in a p L ig a n d ........................................................................................................... 1 0 3


8










R acem ic Z n C ataly st.......... ................................................................ ......... ....... 104
Chiral Zn Catalyst............. .. ...... ............... ........... 107
Co Catalysts................................................... 107
Low Solubility Chiral Ligands ......................................................... ..................... 108
Initial Catalysis Studies .................. ............................ .. ..... ................. 109
C onclusions.....................................................................109
E xperim mental M methods .............................................................................. ......................110
General Considerations .................. ............................... ........ .. ........ .. .. 110
S y n th e sis o f 5 -2 ....................................................................................................1 1 0
S y n th e sis o f 5 -3 .....................................................................................................1 1 1
S y n th e sis o f 5 -4 .....................................................................................................1 1 1
S y n th e sis o f 5 -5 ....................................................................................................1 12
Synthesis of 5-6 ..................................................................... ........ 112
Synthesis of 5-7 ..................................................................... ........ 113
S y n th e sis o f 5 -8 ....................................................................................................1 1 3
S y n th e sis o f 5 -9 ...................................................................................................1 14
Synthesis of racem ic 5-10 .............................................. ......... ............... 114
Synthesis of 5-11 ....... ......... ......... ..................115
Synthesis of 5-12 ...... ......... ...................... ........115
Synthesis of 5-13 ............................................................................ ......... ......... ......... 116
Synthesis of 5-14 ...... ......... ...................... ........116
Synthesis of 5-15 .............. ............................. ............ ........ 117
Synthesis of 5-16 ............................................................................ ............... ...... ........ 117
Synthesis of 5-17 ............................................................................ ............... ...... ........ 117

LIST OF REFERENCES ......... .......... ..................................................................... 133

BIOGRAPHICAL SKETCH .......................................................................... ......... .................. 140
























9











LIST OF TABLES


Table


2-1 X-ray data for the crystal structures of 2-1 and the complexes R,R-2-1, 2-3, and 2-2-
F ................................................................................................ 4 0

4-1 LogKs values of the two salen urea complexes with fluoride, chloride and bromide in
acetone ...........................................................................................84

4-2 X-ray data from crystal structures of 4-2, 4-3, 4-4, 4-6, 4-8..........................................84


page










LIST OF FIGURES


Figure page

1-1 Structure of Park and Simon's katapinate; the first example of an anion binder. ............24

1-2 Structure of azacryptand that is an ideal size match for fluoride....................................24

1-3 Structure of zwitterionic neutral receptor. ................................ .. ........................ 24

1-4 Structure of the pyrrolic m acrocycle sapphyrin. ........................................ ...................25

1-5 Structure of two bicyclic guanidiniums attached by a urethane linker ...........................25

1-6 Structure of neutral anion receptor. ..................................... ... ..................... 26

1-7 Structures of amide based receptors by Bowman-James ........................................26

1-8 Structure of salen complex with uranyl used for Lewis acidic anion binding...................27

1-9 Structure of conjugated polymer that efficiently binds fluoride though phenols. .............27

1-10 Structure of triphenoxymethane platform ........................................... ......................... 27

2-1 Open conformation of CIC chloride channel. .......................................... ............... 40

2-2 Triphenoxymethane platform with the phenols in the "all up" position relative to the
m ethine carbon hydrogen ........................................... ....................... ............... 41

2-3 Procedure used for the synthesis of 2-1, macrocycle metalation to form 2-2, and 2-3
and fluoride binding.................... ......................... ........... 41

2-4 Solid-state structure of 2-1 ....................................................................... ...................42

2-5 Solid-state structure of 2-2 .................................................................... ..... .................. 43

2-6 Solid-state structures of 2-3 .......................................................................................... 44

2-7 H NMR spectrum of 2-3 (top) and [2-3-F] 1 (bottom) taken in d6-DMSO with an
inset of the 19F NMR spectrum of [2-3-F]1- in the region of bound fluoride ...................45

2-8 1H NM R spectrum of 2-2 ........................................................... ............... 45

2-9 1H NMR spectrum of 2-2 with 0.5 equivalents of fluoride added............................... 46

2-10 1H NMR spectrum of 2-2 with one equivalent or more of fluoride...............................46

2-11 UV-Vis titration of 2-2 with tetra-butylammonium fluoride in acetone. ......................47









2-12 Job plot of the titration of 2-2 with tetrabutylammonium fluoride ..............................47

2-12 Absorbance plotted versus concentration of fluoride for the titration of 2-2 at 450nm
with tetrabutylamm onium fluoride. .............................................................................48

2-14 Crystal structure of [2-2-F]1- with fluoride bound in the phenolic pocket....................49

2-15 UV-Vis titration of 2-3 salen with tetra-butylammonium fluoride in acetone.. ................50

2-16 Job plot from UV-Vis spectra titration data of 2-3 in acetone with tetra-
butyam m onium fluoride........................................................................... ....................50

2-17 Absorbance plotted versus concentration of fluoride for the titration of 2-3 complex
at 450 nm with tetrabutylammonium fluoride.............................................. ...............51

3-1 Open conformation of CIC chloride channel. .......................................... ............... 64

3-2 Compound [2-2-F]- with a fluoride hydrogen bonding with the four phenols of the
anion receptor ................. ..........................................................64

3-3 Structure of salen based anion receptor with amine groups at the periphery. The
receptor coordinates both cations and anions ........................................ ............... 65

3-4 Synthetic schem e for Com pound 3-5......................................... ............................ 65

3-5 Synthetic scheme for the synthesis of mixed phenolic-urea salen system (3-7),
metalation at salen binding site and anion coordination (3-8) ........................................66

3-6 Titration plot of 3-7 w ith fluoride ...................................................................... 67

3-7 Depiction of the solid-state structure of [3-8-C1] .................................... .................... 68

4-1 Proposed structure and binding mode of an early urea based anion receptor .................... 85

4-2 Structure of an urea subunit where the anion binding cavity is regulated by metal
c o o rd in atio n ............................................................................ 8 5

4-3 Synthetic scheme for the formation of salen urea (4-1)..................................................86

4-4 Solid-state structure of 4-2 ........................................................................ ..................86

4-5 Solid-state structure of 4-3 ................................................................................ ..........87

4-6 UV-Vis titration of 4-2 with tetra-butylammonium fluoride in acetone.........................88

4-7 Binding constant data of 4-2 titrated with F- at 450nm ...............................................89

4-8 Solid-state structure of 4-4 ......... ................. .................................................................90









4-9 Job plot of 4-2 for chloride ................................................................... .........................9 1

4-10 Solid-state structure of 4-5 ....................................... ............................. ............... 92

4-10 UV-Vis titration of 4-2 with tetra-butylammonium chloride in acetone .........................93

4-12 Binding constant data of 4-2 titrated with C1 at 450nm Log Ks = 5.27 ........................94

4-13 Synthetic scheme for compound 4-6. ........................................ .......................... 77

4-14 Depiction of the solid-state structure of 4-6 ............................. ...............96

4-15 Synthesis ofligand 4-7 and C3 symmetric anion receptor 4-8................ ............. .....97

4-16 Depiction of the solid-state structure of 4-8 ............. ...... ................. .. ............. 98

5-1 Structure of Jacobsen's catalyst used for the asymmetric epoxidation of olefins ...........19

5-2 Proposed mechanism for the epoxidation of olefins with Jacobsen's catalyst..............19

5-3 Structure of catalyst with chiral binapthyl groups that influence the geometry of the
sub state ........................................................................................ 120

5-4 Reaction scheme for the ethyl addition to benzaldehyde................................................120

5-5 Structure of a bifunctional catalyst containing both a Lewis acid and Lewis base
co m p o n en t .............................................................................................12 0

5-6 Enantioselective alkynation of ketones................................................. ............... 121

5-7 Proposed transition state for the alkynation of ketones with a zinc salen catalyst ..........121

5-8 Diels-Alder reaction between cyclopentadiene and cinnamaldehyde promoted by a
Lewis acid catalyst............................ ......... ......... ...... ..........121

5-9 Solid state structure of compound 2-2. ........................................................................122

5-10 Depiction of 2,2-diamino-l1,1-binapthalyene showing the large torsion angle between
the two napthyl planes. ......................................... ........ .............. .. 122

5-11 Synthetic schem e for the synthesis of 5-2.................................. ................................... 123

5-12 Synthetic scheme for the formation of 5-4. ....................................... ............... 123

5-13 Solid state structure of compound 5-4 ................................. 124

5-14 Solid state structure of 5-6 ....................................................................... ..................125

5-15 Solid state structure of compound 5-7. ............. ...... ........................................... 126









5-16 Solid state structure of the dinuclear catalyst 5-8. ................................... .................. ... 127

5-17 Space filling model of the solid state structure of 5-8. ....................................................128

5-18 1H NMR spectrum of the paramagnetic compound 5-9.............................128

5-19 Solid state structure of the dinuclear compound 5-10 .....................................................129

5-20 Schematic of triphenoxymethane aldehyde showing its possible positions for ligand
m modification. ..............................................................................129

5-21 Synthetic scheme for compounds 5-11 and 5-12.................................. ............... 130

5-22 Synthetic scheme for the synthesis of 5-13 and 5-14 ............................................... 130

5-23 Schematic diagram of the structures of 5-15, 5-16, and 5-17 ........................................ 131

5-24 Crystal structure of 5-16; Co (II) is arranged in an octahedral geometry .......................131

5-25 Catalytic reaction of the ethyl addition to benzaldehyde used as a standard to monitor
the catalytic ability of the compounds ............... ................ ........... ... ............ 132









Abstract of Dissertation Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy

METAL SALEN COMPLEXES IN ANION BINDING AND CATALYSIS

By

Eric R. Libra

August 2007

Chair: Michael J. Scott
Major: Chemistry

Most forms of life require the recognition and transportation of anions. There have been

numerous efforts to develop synthetic receptor systems that are both efficient and selective for

the coordination of anions. Nature often employs the use of OH groups for anion coordination,

yet this binding mode is one that has not been explored in the area of synthetic anion receptor

design. A series of substituted metal salen compounds have been developed that show a high

affinity for the coordination of anions. The rigid metal salen macrocycle can orientate four

phenol groups into a tetrahedral array that tightly and selectively binds fluoride through four

strong OH-F hydrogen bonding interactions. The size of the anion binding cavity can be

regulated by the incorporation of different metal centers, enabling the properties of the system to

be modified. Metals also offer convenient pathways to report the binding event via spectral

changes from the strong metal to ligand charge transfer transitions, making these receptors anion

sensors. Not only can the metal salen system organize groups for anion binding, they can also be

used as chiral catalysts. The synthesis of a rigid and sterically bulky metal salen complex has

been undertaken for the use as an asymmetric catalyst to promote organic transformations.









CHAPTER 1
INTRODUCTION

Anions are ubiquitous in a variety of chemical and biological systems. For complex

forms of life to exist, many biochemical processes require the recognition and transportation of

anions.2 A number of enzyme substrate interactions rely on anions and it is reported that anions

exist in about 70% of all enzymatic sites where they play a key role in enzyme substrate

interactions, as well as having important structural roles in proteins.2 The malfunction of

channels that facilitate anions across cell membranes, especially chloride,3 is considered the

primary cause of many diseases including cystic fibrosis,4 Bartter's syndrome,5 Dent's disease,6

Pendred's syndrome,7 and osteopetrosis.8

Over the last 25 years there have been numerous efforts to create systems for anion

coordination.9 The development of selective anion receptors is difficult compared to those

designed for selective cation complexation, as anions are typically larger than their isoelectronic

cationic counterparts and thus typically have a more diffuse charge. Solvent and pH concerns

also play major roles in anion complexation and the nature of coordinating solvents often

regulates anion binding and selectivity. Captions are able to form covalent or dative bonds

readily to receptor systems while anions must rely on weaker electrostatic forces such as

hydrogen bonding or Lewis acidic interactions.10

There are many examples of anion recognition by host molecules containing various

structural and binding modes.11 Some of these systems are able to signal the binding event,

which is often done by incorporating various substituents that have the ability to "report" the

anion coordination process.12 Some sensors display a change in color or fluorescence upon

interaction with anions, and the ability to readily detect the binding event has recently become an

important aspect of anion receptor design.13'14 The ability to determine on the macroscopic level









what is happening at the molecular level, such as the coordination of an anion guest into a host

molecule may lead to the qualitative and/or qualitative sensing of certain guest molecules.1

Although there has been much work done in the field of anion binding; the area of anion sensing

is far less explored.

Anion Coordination Modes

The creation of molecules that coordinate anions is considered to be in the realm of

supramolecular chemistry.15 The interactions involved in these systems are between molecular

or ionic molecules and a guest anion which exist without the formation of covalent bonds. Most

of the effort to design anion receptors has focused on the use of Lewis acidic metals16 or organic

ligands that employ hydrogen bonding or electrostatic interactions.17 Hydrogen bonding has

shown to be the binding motif that best induces selectivity of a specific anion,18 as it is difficult

to regulate the direction of Lewis acids, while hydrogen bond donor groups can easily be

arranged in a multitude of geometries. There are many potential applications of anion sensors as

they can selectively recognize a large variety of anions ranging from fluoride to DNA.1,9, 17

Hydrogen bonds are common in chemical systems as they often have an effect on

molecular structure and mechanistic properties19 and are among the most well utilized means of

anion coordination. A hydrogen bond is an attractive interaction between a hydrogen atom and

an electronegative atom when the hydrogen is covalently bound to an electronegative donor such

as oxygen or nitrogen20 and the strength and length of the hydrogen bond is influenced by the

nature of both the donor and receptor atoms.21

For the design of anion receptors one must select the proper donor, its orientation within

the molecule and also regulate the size and geometry of the binding cavity. To provide hydrogen

bond donors in a particular system, groups such as amides, amines, pyrroles, and ureas are

normally used.22 N-H groups are relatively easy to preorganize and the majority of the current









examples of anion binding systems have employed this moiety to achieve this goal. Herein, this

review will briefly examine the history and progress in the field of synthetic anion receptors.

Initial Studies of Anion Receptor Systems

Selective anion binding has been a topic of interest for almost 40 years since the first anion

binding receptor was reported in 1968 by Park and Simon, who showed that bicyclic diaza

katapinands (Figure 1-1) could coordinate to halide ions.23 Park and Simon correctly predicted

that hydrogen bonding and not the positive charge of the system was the main mode for halide

complexation. Although the binding constants were modest with a logKs value of 2, it set the

stage for an entire field of research including that of macrocyclic ammonium based receptors.

This research area began to grow in the 1970's when Lehn began coordinating anions with

polyammonium macrocycles.24 Lehn's work demonstrated that anions could be selectively

coordinate based on size and the design of certain receptors and binding cavities led to stronger

interactions with certain anions. For example, a receptor that was an ideal size match for

chloride was developed and had a logKs value of 4 while iodide was too large to coordinate

within the binding cavity and thus had a much lower binding constant.

Lehn and coworkers also noted that particular receptors showed a wide range of stability

constants for different anions not only of different sizes, but also geometries. An elliptical

shaped receptor was designed that was selective for the linear shaped azide, while it had a low

binding constant for chloride.25 The accommodation of chloride into the cavity had no geometric

constraints, but it did not have the ideal fit that azide did. Due to these observations new

synthetic cavities were developed with the intention of accommodating certain anions by

incorporating geometric and spatial constraints. The structure seen in figure 1-2 has shown to be

a superb size compliment to fluoride as determined by its solid state structure,26 and this size

compatibility has led to an extremely high binding constant oflogKs = 11.2, which is 107 times









larger than its binding constant for chloride.27 The strategy of creating a size and geometrically

selective cavity for anion coordination became extremely prevalent and is now a basic

requirement for the design of any receptor system.

Various quaternary ammonium based anion binders were developed that did not employ

hydrogen bonding interactions, but rather arranged ammoniums into a cavity. By adjusting the

length of the carbon linkers between the ammoniums, the cavity size could be altered and

selectivity could be affected.28 Receptors with a positive charge must contain counter ions which

are in direct competition for the anion binding sites. Schmidtchen and coworkers were able to

develop a zwitterionic receptor that has an overall neutral charge and avoids the problems

incurred by the counter ions.29 The creation of a size selective, neutral receptor that does not

employ hydrogen bonding interactions is in contrast to most other systems, yet there has been

little work in this area due to synthetic challenges.

Pyrrolic Macrocycle Receptors

After this seminal work was introduced, the field of receptor chemistry exploded with

activity. Pyrrolic macrocycles have been among the most versatile and useful molecules for

anion binding, as pyrroles do not contain groups that may induce self association.1 The ease to

which they can be functionalized and ability to make cyclic variations greatly increases the

opportunities to tune the system and this has led to the design of pyrrolic systems of many

different sizes, shapes, structures, and electronic properties.

Sapphyrins are a common pyrrolic macrocyclic system for anion coordination30 and was

first seen as an anion binder in the work of Sessler and co-workers, who reported a crystal

structure of a diprotonated sapphyrin with a fluoride bound in the core.31 The initial structure

with a fluoride ion coordinated was obtained accidentally, but after this observation other anions

were tested and modifications to the sapphyrin were made to tune the properties of the system.









Based on the examination of the solid state structure of the complex, chloride was found to be

too large to fit inside the center core of the receptor. Instead, two chloride ions were positioned

and coordinated above the plane of the receptor.32 Sapphyrins are highly colored and anion

coordination leads to changes in the absorption and admission spectra of the molecule, making it

an anion sensor. The measurement of these spectroscopic changes leads to high binding

constants for fluoride, chloride, and bromide with logKs values of 8.0, 7.2, and 6.1 respectively.32

Biologically Relevant Receptors Incorporating the Guanidinium Group

While pyrrolic macrocycles are effective anion receptors, there are many other systems that

incorporate N-H groups for anion coordination. The guanidinium ion has been extensively

studied because of its prevalence in nature. Guanidiniums are present in arginine residues and

are responsible for many hydrogen bonding interactions in biology. This group contains two N-

H hydrogen bond donors as well as a delocalized positive charge that contribute to its strong

interactions with the guest species. Guanidinium has a pKa of 13.5 which results in protonation

of this moiety over a wide pH range where it will retain both its positive charge and hydrogen

bond donor properties.33 Many synthetic systems incorporating the guanidinium group, such as

the molecule in Figure 1-5, have been successful anionic binders since it forms both electrostatic

and hydrogen bonding interactions with anionic molecules.

Neutrally Charged Receptors

The presence of positive charges on a receptor system may be helpful for anion coordination,

but it also leads to several problems in efficiency and selectivity. In a charged species, it is

difficult to regulate the nondirectional electrostatic forces, so adjustments to a particular system

become more complicated. The existence of counter ions also causes problems as they are in

direct competition for binding sites which affects the selectivity and efficiency of the receptor.1

The synthesis of neutral species eliminates many of these issues and they have proven to be









amongst the best selective receptors. Reinhoudt and coworkers were one of the first groups to

use very simple neutral host molecules as anion hosts. Figure 1-6 depicts an example of a

structure that incorporates N-H hydrogen bond donors to coordinate H2P04- selectively over

HS04- and C1- with a logKs of 4.1.35

The use of N-H donors exists in numerous examples of simple acyclic receptor systems

and small modifications have shown to effect anion binding ability and selectivity.36 The

creation of cyclic or cage-like molecules however, has rigidified the molecules by placing less

flexible spatial constraints on the anion. Recently Bowman-James and co-workers have

developed a polyamide cryptand that has shown to bind anions.37

Linking two sets of amides together as outlined in figure 1-7 will create a cavity with

multiple N-H groups directed towards the center. Receptor A has shown to bind strongly with

phosphate and sulfate and it is believed that the strong interactions are a result of the high

correspondence of geometry and size between the guest and host. Amines can deprotonate the

anion causing even stronger binding interactions. The tren based bicyclic aza cryptands (Figure

1-7, B) are neutrally charged and have shown to bind fluoride with a high efficiency. Crystal

structures of the cryptand with both fluoride and chloride show the halides coordinated within

the central cavity and there has also been a noted affinity for other halides as well as for H2P04-.

Anion Coordination Through Lewis Acidic Metals

Although hydrogen bonding and electrostatic interactions are the common modes of anion

complexation, they are not the only available methods. Receptors containing Lewis acidic

metals are capable of providing an anion binding site and typically incorporate centers such as

boron, silicon, mercury and tin.38 Since many anions are coordinatively saturated the donation of

electrons to a Lewis acidic metal forms a strong interaction between the two.









Reinhoudt and co-workers have incorporated a uranyl into the backbone of a salen

macrocycle (Figure 1-8) and is able to coordinate anions through this Lewis acidic site.39 The

coordination of H2P04 occurs through both the Lewis acidic uranyl as well as a stabilizing force

from the acetoamido groups.40 Salens can also act as receptors for Ni (II) and Cu (II) sulfate

when amine groups are bound at the periphery of the macrocycle.41 This receptor is able to

coordination an anion and a cation into the same complex. There is great potential in the further

exploration of anion receptor systems with the salen macrocycle as they provide an excellent

building block for the incorporation of a variety of binding groups.

The synthesis of the salen based ligands is relatively easy and a wide range of donor

groups can be readily attached to the system. The incorporation of a metal center into the

macrocylic rings rigidifies the structure can also make these molecules suitable for anion sensing

since metal salen compounds normally exhibit strong MLCT transitions in the visible region.

The binding event can often be followed by monitoring the position of this intense absorption

band. The size of the binding cavity can also be regulated by the incorporation of metals of

different radii affecting the binding constants for different anions.

Hydrogen Bonding Interactions Through Oxygen Donors

The use of O-H donor groups interacting with anions in biological systems is extensive.

For example, some protein recognition processes rely on an interaction between hydroxyl groups

on a carbohydrate and an anionic protein.42 In spite of the utility of hydroxyl groups in nature;

almost all synthetic receptor systems use some combination of N-H groups. There have been

only a handful of examples of complexes that bind anions with an O-H group and none of them

are particularly well defined systems. The O-H group can form strong hydrogen bonding

interactions but the deficiency of O-H donor examples may be due to the synthetic difficulty in

preorganizing such groups. Simple, off the shelf, phenols such as catechol can coordinate









anions, although not surprisingly with rather low binding constants.43 Since then only a handful

of other systems incorporating O-H donors have been developed including the work by Wang

and coworkers who have created a conjugated polymer system that shows selectivity for fluoride

and phosphate.43'44

The extremely limited body of work for O-H donors in synthetic anion receptor systems,

while surprising, offers the opportunity to make important contribution to this field. Presumably,

most receptors employ N-H donors opposed to O-H groups as they are relatively easy to

organize. Creation of a binding cavity utilizing O-H groups has proven synthetically

challenging. In previous work with the pre-organization of phenols, our group has developed the

triphenoxymethane molecule (Figure 1-10) and noted that it prefers an "all up" configuration,

where all three phenols are pointed in the same direction with respect to the central methine

carbon.45 This molecule is readily modified and its properties can easily be tuned.

Research Objectives

Our objective is to incorporate the triphenoxymethane molecule into the backbone of a

salen macrocycle for the use of selective anion sensing. We envisioned creating a cavity of

phenolic donors offering four O-H groups available for anion coordination. This type of

molecule would be the first example of a well defined receptor system that employs purely

hydroxyl groups. As described above, the salen system was chosen for its ability to provide a

visual report, allowing the binding event to be monitored by UV-Vis spectroscopy. The choice

of metal also plays an important role in structurally regulating the cavity size. Herein, we report

the design, synthesis and study of metal salen complexes and their anion binding properties.








(CH2)1n


N-H X H-N

(CH2 n

(CH2),

n= 7-10


Figure 1-1. Structure of Park and Simon's katapinate; the first example of an anion binder.



NH HN
H
NNN N
H
NH HN


Figure 1-2. Structure of azacryptand that is an ideal size match for fluoride and shows an
extremely high binding constant for fluoride (logKs = 11.2)


H3BO


X = -(CH2)6-


Figure 1-3. Structure of zwitterionic neutral receptor. Anion coordination is done through
electrostatic interactions only.

























Figure 1-4. Structure of the pyrrolic macrocycle sapphyrin. Upon protonation there are five N-
H's donors that form hydrogen bonds to anions.




HO OH

NH HN

N NH2 HN N

F', o 0 N N 0H b




Figure 1-5. Structure of two bicyclic guanidiniums attached by a urethane linker.













HN
RO2SN HNS2R

N SO2R


Figure 1-6. Structure of neutral anion receptor.


A B


Figure 1-7. Structures of amide based receptors by Bowman-James



























Figure 1-8. Structure of salen complex with uranyl used for Lewis acidic anion binding


Figure 1-9. Structure of conjugated polymer that efficiently binds fluoride though phenols.


HO


R = t-bu
"all up"

Figure 1-10. Structure of triphenoxymethane platform with three phenols aligned with respect to
each other.









CHAPTER 2
METAL SALEN COMPLEXES INCORPORATING TRIPHENOXYMETHANES:
EFFICIENT, SIZE SELECTIVE BINDING OF FLUORIDE WITH A VISUAL REPORT

Introduction

For the design of anion receptors, Lewis acidic metals16 or organic ligands that employ

hydrogen bonding and/or electrostatic interactions are often used.10 In the case of hydrogen bond

donors, virtually all of the attention has focused on ligands incorporating N-H groups such as

amides, amines, pyrroles, and ureas,22 and in some instances, metals help orient these groups.46

Surprisingly, despite the wide participation of serine and tyrosine hydroxides in anion binding

sites in biological systems including C1C chloride channels47 and Bacteriorhodopsin48 among

numerous others,49 the use of O-H donors in the design of anion receptors has been limited to

only a handful of examples that are not particularly well defined systems.50

To provide hydrogen bond donors to coordinate anions, N-H as well as O-H donor groups

can be used. A hydrogen bonding interaction can take place between a hydrogen covalently

bound to an electronegative donor and an electronegative acceptor (D-H-..A). The limited work

in the area of O-H based anion receptors may be due to the difficulties in pre-organizing O-H

groups compared to N-H groups. The phenolic proton is quite acidic (pKa -10) compared to that

of amines (-26) and amides (-20) and thus O-H groups should form stronger hydrogen bonds

than those formed by N-H groups.

Results and Discussion

The presence of O-H groups can increase the affinity of N-H containing ligands for

anions,51 but we envisioned that a tetrahedral pocket of phenolic donors templated by a metal

could provide an ideal environment for the selective binding of anions, particularly since the size

of the cavity could be modulated by the choice of metal. Metals also offer convenient pathways

to report the binding event via spectral changes. Salens have been engineered to orient two sets









of N-H donors by several groups,52 and herein, we report the synthesis and attributes of an anion

receptor incorporating four phenols at the periphery of salen.

Advantages of the Salen Macrocycle

In previous work with triphenoxymethanes44 (Figure 2-2), a profound preference has been

noted for the molecule to adopt an "all-up" orientation wherein all three phenolic oxygens align

with respect to the central methine hydrogen. A derivative incorporating an aldehyde group on a

single phenol can be readily isolated.53 The molecule reacts with 1,2-diamino cyclohexane to

form 2-1 as outlined in Figure 2-3.

A range of metals including Mn (II), Ni (II), Zn (II), and Pd (II) can be incorporated into

the salen binding sites without affecting the four remaining phenols. The six triphenoxymethane

phenols still prefer to remain aligned, and since the metal coordinates to two of them, a pocket is

created which is lined by four hydrogen bond donor groups in a pseudo tetrahedral arrangement.

Initial work on the development of an anion sensor has focused on the diamagnetic, square

planar Ni (II) and Pd (II) metals since their radii differ by approximately -0.15 A, providing the

opportunity to adjust the size of the binding cavity. Salen complexes with these metals also

exhibit intense MLCT absorptions (F 7400) in the visible region.54 The relative synthetic ease

of the system and the possibility to tune the receptor's properties by complexation of different

metals offers many advantages and the synthesis of the receptor is seen in Figure 2-3.



Design of Receptor System

Compound 2-1 has been structurally characterized (Figure 2-4) and in the solid-state, the

two sets of triphenoxymethanes align themselves on opposite sides of the 1,2-

diaminocyclohexane linker. The phenols remain aligned in the same direction with respect to









each other. The incorporation of a metal center into the ligand aligns and rigidifies the molecule

positioning the four remaining phenols into tetrahedral environment.


For the development of an anion sensor, focus has been placed on the diamagnetic,

square planar Ni (II) and Pd (II), providing the opportunity to adjust significantly the size of the

binding cavity. Ni (II) and Pd (II) are also d8 and prefer a square planer geometry which makes

them diamagnetic and enables us to follow the synthesis and anion binding by NMR

spectroscopy. Salen complexes with these metals also exhibit intense MLCT absorptions (F ~

7400) in the visible region54 and the compounds have shown significant color change upon

addition of fluoride.


Both Ni (II) (2-2) and Pd (II) (2-3) metal complexes with 2-1 were structurally

characterized, and in each, two symmetry independent molecules crystallized in the asymmetric

unit. In both cases, the molecules were nearly indistinguishable, but the orientation of the

unbound phenols with respect to the chiral centers on the cyclohexyl rings differed. The chiral

R,R-cyclohexyl backbone was used to isolate single crystals of 2-2 and the structure of one of the

two symmetry independent molecules is presented in Figure 2-5. The chiral R,R-1,2-

diaminocyclohexane backbone as well as the racemic version was used to isolate the Ni (II)

complex. There were significant differences in solubilities between the two molecules yet they

showed identical UV-Vis and NMR spectra. While the racemic complex had a limited solubility

the chiral receptor was soluble in solvents with a wide range of polarities.

As expected, the average distance of the four Ni-oxygen bonds in the two complexes

(1.842(8) A) are typical for a Ni (II) salen complex55 but significantly shorter than the

corresponding average Pd-oxygen distances (2.009(4) A). The subtle size difference between the

two metals produces a profound increase in the separation between the two sets of phenolic









donors attached to the salen backbone. The distance between the two methine carbons, C (15)

and C (46), increases from 5.28 A in 1-Ni (II) complex to 6.03 A in the 1-Pd (II), and this

increase manifests other changes. In both symmetry independent Ni (II) complexes, a phenolic

group from each side of the cavity maintains short hydrogen bonding interactions with the salen

phenolates (0-0 separations vary from 2.677(7) A to 2.885(9) A) and the two remaining

phenolic oxygens are situated 2.762(7) A or 2.784(8) A from each other, creating a cavity held

together by several intramolecular hydrogen bonds. In contrast, only a single phenol hydrogen

bonds to the salen phenolate in the cavity formed in 2-3 with a 0-0 separation of 2.824(4) A,

and this oxygen also maintains a close contact of 2.804(4) A with a phenol oxygen on the

opposite side of the cavity. The remaining two phenols are more than 3.989 A from the nearest

oxygen. These intramolecular hydrogen bonding interactions not only play a structural role, but

may also have an effect on the colorimetric properties of this system.

Anion Binding Properties

Anion binding properties of the two metal complexes were tested with n-Bu4N+ halide salts

in a variety of solvents including chloroform, acetone, and DMSO, and both 2-2 and 2-3

complexes only reacted with fluoride at low anion concentrations. The binding cavity appears to

be too small to accommodate the larger anions and even after the addition of a large excess of C1-

, Br-, I, NO3-, C104-, or HS04- no changes could be detected in the H NMR or UV/Vis spectra.

Treatment of 2-2 and 2-3 with one equivalent of more basic anions such as H2P04- and OAc-

produced no discernable change in the UV/Vis or 1H NMR spectrum other than the

disappearance of the OH resonances in the 1H NMR spectrum, but at very high concentrations (>

30 eq), the anions induced precipitation in the NMR experiment and a small (<8 nm) shift of the

absorption maxima in the UV/Vis spectra of the complexes.









In contrast, the addition of fluoride to 2-2 induced a dramatic change in the 1H NMR

spectrum, and with any amount less than a full equivalent of fluoride, the spectrum was quite

broad, suggesting a rapid equilibrium of fluoride between open binding sites since the complex

remains diamagnetic. Unfortunately, cooling of the sample initiated crystallization and variable

temperature NMR experiments could not be performed. Addition of fluoride to 2-3 produced a

less dramatic effect on the 1H NMR spectrum of the complex (Figure 2-7), and the only

significant change involved the two resonances associated with the phenolic protons that shift

from 6.83 and 6.44 ppm in d6-DMSO and appear as a doublet at 9.93 ppm (JHF = 46 Hz).

Similar magnitudes for H-F coupling constants have been noted in halide receptors

incorporating amides56 and pyrroles.57 The phenolic resonances for [2-2-F]1 also occur as a

doublet downfield at 9.69 ppm (JHF = 42 Hz) in d6-DMSO, but in solvents such as CDC13 and

(CD3)2CO, the resonances for the phenolic protons on both 2-2 and 2-3 are absent, presumably

due to deuterium exchange with solvent. Fluoride is known to facilitate deuterium exchange on

amides in halide receptors.58 In the 19F NMR spectrum, a quintet resonance (JHF = 46 Hz) slowly

grows in at -117.2 ppm (referenced against trifluorotoluene at -63.7 ppm) as fluoride is added to

a d6-DMSO solution of 2-3, intimating that the four phenolic O-H.**F interactions are equivalent

and produce the 2nl + 1 quintet resonance.

After addition of more than a one equivalent of anion, a new resonance arises at -145.7

ppm, the normal position of the resonance of free fluoride ion. The 19F NMR spectrum of 2-2

after addition of fluoride exhibited a broad resonance at -116.2 ppm, and the value for the H-F

coupling constant could not be accurately determined. Once again, solvents such as chloroform

and acetone favor deuterium exchange, and all H-F coupling in the 19F NMR disappear in these

solvents.









Addition of fluoride to 2-2 and 2-3 disrupts the hydrogen bonds to the salen phenolates

and induces a red shift in the MLCT absorption with two distinct isobestic points (Figure 2-11),

intimating a single species forms in solution. In the case of 2-2, the absorption shifts from 411

nm to 431 nm with a small decrease in the molar absorptivity while the 2-3 exhibits a slightly

larger shift from 407 nm to 440 nm. The color change is abrupt and can easily be seen by the

naked eye.

The determination of the binding mode of the anion and the ratio of bound anion to

receptor requires the production of Job plots. Both 1HNMR and UV-Vis spectral data are

commonly used to derive Job plots, but due to the complicated nature of 1H NMR spectrum and

the clarity of the absorption data for 2-2, UV-Vis spectra were used to determine the guest-host

stoichiometry. The location of the apex of the plot indicates the ratio of fluoride bound to each

2-2 molecule. A Job plot for the spectral data of 2-2 shows a maximum at 0.5 indicating a

single equivalent of fluoride binds in the phenolic cavity (Figure 2-12).

Binding Constants

The binding constants (Ks) were determined from the data obtained by UV-Vis spectroscopy

fluoride titrations. The measured absorbance were plotted as a function of fluoride ion

concentration of the solution at 450nm and a non-linear least squares regression was used to

determine binding constants with the equation:59 X = Xo + [(Xim Xo) / 2co] [co + cm +1/Ks -

[(co + cm + 1/Ks)2 4cocm]1/2]. In this equation, X is the measured absorbance, Xo is the initial

absorbance, Xlim is the limiting absorbance, co is concentration of anion in solution, cm is the

concentration of the receptor, and Ks is the binding constant. A program to perform a non-linear

least squares regression on the data60 which minimizes the error of each data point to fit the

standard equation by altering Ks was written in excel. The value of Ks that leads to the lowest

sum of errors is the binding constant for the system. The logKs values (errors 10%) were









determined to be 5.6 for 2-2 and 5.8 for 2-3 in acetone (logKs = 5.8 for both complexes in

DMSO).

Solid State Structure of [2-2-F]1

Single crystals of the 2-2 with a fluoride ion were obtained, and in the solid state (Figure 2-

14), the fluoride is held in the phenolic cavity by three short and one long hydrogen bond to form

[2-2-F]1- (fluorine oxygen separations of 2.539(2) A, 2.509(2) A, 2.573(2) A, and 3.098(3) A).

Although the resonances are a bit broader than the data presented in Figure 3 for [2-3-F] 1, the

solution NMR spectra for [2-2-F]lsuggest the fluoride is held in a symmetric environment by the

four phenols, and the lone, long OH.**F interaction may be an artifact of crystal packing.

In order to fit the anion, the phenolic pocket has had to open up, and the separation

between the methine carbons, C(15) and C(46), has increased by almost 0.5 A to 5.73 A in

comparison to 2-2. Ni (II) appears to be resisting the increase in size of the cavity, and the metal

distorts from planarity with an angle of 15.8 between the two N-Ni-O planes in the salen. The

cavity created by the Pd(II) center should be able to accommodate the fluoride anion with much

less distortion, since the separation between C(15) and C(46) is already 6.03 A in 2-3 which may

lead to the larger Ks (logKs = 5.81) compared to that of 2-2. The clarity of the 1H NMR spectrum

of 2-3 during the titration experiment suggests structural distortions are less pronounced than in

2-2.

Anion Binding Studies for 2-3

Binding studies of compound 2-3 were tested with the various anions and the increase in

cavity size for 2-3 between the methine carbons to 6.03A compared to 5.23A in the Ni complex

was quite dramatic and the ability to bind larger anions was a possibility. As with 2-2, 2-3 had a

profound affinity for fluoride while showing no interaction with other anions. Titration

experiments with tetrabutylammonium salts in acetone, and once again showed there was no









change in the NMR spectra or UV-Vis spectra from C1-, Br, I, NO3-, C104-, or PO43-. Titration

of 2-3 with fluoride led to a large red shift in the absorbance spectra, where the main absorption

shifts from 407 nm to 440 nm. There were also two isobestic points for this titration implying

only a single product is formed. The job plot for 2-3 shows that fluoride binds to the Pd complex

in a 1:1 ratio (Figure 2-16).

Even though the cavity of 2-3 is considerably larger than 2-2 it is still size selective for

fluoride and can not accommodate other large anions. The ionic radius of fluoride is

considerably smaller than that of most other anions at 1.36A, such as chloride (1.81A), and

phosphate (2.38A).

The larger cavity does have an effect on the binding ability of fluoride and influences

several of the properties of 2-3. The 1H NMR spectrum of 2-2 with less than one equivalent of

fluoride is very complicated possibly due to a fast exchange of fluoride between open binding

sites. However, compound 2-3 has only minor changes in the spectrum other than the

disappearance of the peaks representing the two different phenols in the structure. Due to the

increased cavity size there is potentially a lack of strain places on 2-3 upon binding fluoride

eliminating the exchange that is seen with 2-2. Another consequence is the slightly higher

binding constant of 2-3 which has a logKs of 5.81 compared to 2-2 which has a logKs of 5.64.

Conclusions

In conclusion, a salen ligand, 2-1, has been designed with a pair of phenolic donors

tethered to the ortho-position of each of the salen phenols. Complexation of square planar metal

centers into the macrocyclic binding pocket forces the four remaining phenolic groups to form a

tetrahedral array, and this pocket tightly binds fluoride. The ion is bound by three short and one

long O-H***F interactions, representing a rare example of efficient anion binding by purely OH

hydrogen bonding in a well-defined sensor The binding event induces a red-shift in the intense









MLCT transition, offering a distinct visual report of the binding event. Efforts to increase the

size and the number of phenolic donors that create the cavity by using different metal centers and

amine linkers are currently underway.

Experimental Methods

General Considerations

1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at

299.95 and 75.47 MHz for the proton and carbon channels. UV-Vis spectra were recorded on a

Varian Cary 50 spectrometer. Elemental analyses were performed at either the in-house facility

of the Department of Chemistry at the University of Florida or by Complete Analysis

Laboratories Inc., Parsippany, NJ. All solvents were ACS or HPLC grade and used as

purchased. For the metalation reactions, the solvents were dried with a Meyer Solvent

Purification system.

Synthesis of 2-1

A portion of 0.63 g (5.52mmol) of 1,2-diaminocyclohexane was dissolved in 50 mL

absolute ethanol. To this solution a slurry of 5.00 g (11.05 mmol) of 3-(2,2'-Methylenebis (4-

methyl-6-tert-butylphenol)-5-methyl-2-hydroxybenzaldehyde53 in 300 mL ethanol was added.

The reaction was refluxed open to the air for 12 hours. The solution was cooled to room

temperature and water was added to the solution resulting in the precipitation of a bright yellow

solid. The solid was filtered and dried to afford the product in 83% yield (4.73 g). 1H NMR: 6

8.12 (s, 2H); 7.04 (s, 4H); 6.93 (s, 2H); 6.77 (s, 2H); 6.66 (s, 4H); 5.94 (s, 2H); 5.62 (s, 2H); 5.40

(s, 2H); 3.30 (d, 2H); 2.20 (s, 6H); 2.17 (s, 6H); 2.10 (s, 6H); 2.00-1.85 (m,); 1.38 (s, 36H). 13C

NMR 6 165.4; 157.7; 151.4; 137.7; 134.5; 131.2; 129.2; 128.3; 127.9; 127.7; 127.5; 117.9; 72.0;

39.2; 34.9; 33.2; 30.0; 24.33; 21.3; 20.7. HR-FABMS: calcd for C68H8706N2 1027.6564; found

1027.6568 [MH+]. IR: v [cm-1] 3495 (OH); 1625 (C=N).









Synthesis of R,R-2-1

Using a modified literature procedure,61 a portion of 2.00 g (7.57 mmol) of (R,R)-(-)-1,2-

diaminocyclohexane mono-L-(+)-tartrate was mixed with 2.09 g (15.14 mmol) of potassium

carbonate and dissolved in 15 mL water. To this solution, 60 mL of absolute ethanol was added

and the solution was brought to a reflux. A slurry of 6.85 g (15.14 mmol) 3-(2,2'-Methylenebis

(4-methyl-6-tert-butylphenol)-5-methyl-2-hydroxy-benzaldehyde in approximately 150 mL of

ethanol was slowly added to the amine with an addition funnel. The solution was then refluxed

for three hours. 20 mL of water was added and it was cooled in the refrigerator for 12 hours.

The bright yellow solid was filtered and then dissolved in methylene chloride. It was washed

three times with water in a separatory funnel, dried with magnesium sulfate and the solvent was

removed to afford the pure product in 78% yield (6.05 g). 1H NMR: 6 8.12 (s, 2H); 7.04 (s, 4H);

6.93 (s, 2H); 6.77 (s, 2H); 6.66 (s, 4H); 5.94 (s, 2H); 5.62 (s, 2H); 5.40 (s, 2H); 3.30 (d, 2H); 2.20

(s, 6H); 2.17 (s, 6H); 2.10 (s, 6H); 2.00-1.85 (m,); 1.38 (s, 36H). 13C NMR 6 165.4; 157.7;

151.4; 137.7; 134.5; 131.2; 129.2; 128.3; 127.9; 127.7; 127.5; 117.9; 72.0; 39.2; 34.9; 33.2;

30.0; 24.33; 21.3; 20.7.

Synthesis of R,R-2-2

A portion of 1.0 g (0.974 mmol) R,R-1-H2 was dissolved in dry THF. To this solution

0.27 g (10.30 mmol) of nickel acetate was added and it was refluxed under nitrogen for 12 hours.

The solution was cooled, filtered and the solvent removed. The remaining solid was then

dissolved in pentane, filtered and a dark red solid was obtained in an 87% yield (0.92 g).

Crystals suitable for X-ray diffraction were grown by slow evaporation from a concentrated

acetonitrile solution. 1H NMR: 6 7.45 (s, 2H); 7.17 (d, 2H); 6.87 (s, 4H); 6.83 (s, 2H); 6.76 (s,

4H); 6.57 (s, 2H); 6.38 (s, 2H); 6.25 (s, 2H); 3.20-3.15 (m, 2H); 2.55-2.45 (m, 2H); 2.17 (s, 6H);

2.14 (s, 12H); 2.00-1.9 (m, 2H); 1.12 (s, 18H); 1.11 (s, 18H). 1C NMR 6 158.2; 152.0; 151.8;









137.5; 137.3; 137.2; 132.2; 130.6; 128.9; 128.6; 127.4; 127.3; 126.6; 126.8; 119.6; 70.3; 36.4;

34.6; 29.5; 28.7; 24.4; 21.0; 20.4. Anal. Calc. for C68H84N206Ni CH3CN: C, 74.72; H, 7.79; N,

3.73. Found C, 74.24; H, 7.84; N, 3.44.

Synthesis of 2-2

A portion of 1.0 g (0.974 mmol) of l-H2 was dissolved in dry THF. To this solution 0.27

g (1.07 mmol) of nickel acetate was added and it was refluxed under nitrogen for 12 hours. The

solution was cooled, filtered and the solvent removed. The solid was then washed with pentane

and filtered producing a red solid product in 91% yield (0.96 g). H NMR: 6 7.45 (s, 2H); 7.17

(d, 2H); 6.87 (s, 4H); 6.83 (s, 2H); 6.76 (s, 4H); 6.57 (s, 2H); 6.38 (s, 2H); 6.25 (s, 2H); 3.20-

3.15 (m, 2H); 2.55-2.45 (m, 2H); 2.17 (s, 6H); 2.14 (s, 12H); 2.00-1.9 (m, 2H); 1.12 (s, 18H);

1.11 (s, 18H). 13C NMR 6 158.2; 152.0; 151.8; 137.5; 137.3; 137.2; 132.2; 130.6; 128.9; 128.6;

127.4; 127.3; 126.6; 126.8; 119.6; 70.3; 36.4; 34.6; 29.5; 28.7; 24.4; 21.0; 20.4.

Synthesis of 2-3

Using a modified literature procedure,62 a portion of 1.00 g (0.974 mmol) of 1-H2 was

dissolved in dry ether. To this solution 0.092 g (2.14 mmol) sodium methoxide was added along

with 0.240 g (1.07 mmol) of palladium acetate. The solution was refluxed for three hours under

nitrogen during which time a green precipitate formed. The solution was cooled and the

precipitate was filtered. The product was redissolved in methylene chloride, filtered and then

solvent was removed leaving a yellow solid in a 62% yield (0.68 g). Crystals suitable for X-ray

diffraction were grown by a chloroform / pentane diffusion. 1H NMR: 6 7.57 (s, 2H); 7.10 (d,

2H); 6.98 (s, 4H); 6.95 (s, 2H); 6.91 (s, 2H); 6.88 (s, 2H); 6.60 (s, 2H); 6.58 (s, 2H); 6.28 (s, 2H);

5.81 (s, 2H); 3.50-3.40 (m, 2H); 2.41 (d, 2H); 2.16 (s, 6H); 2.14 (s, 6H); 2.09 (s, 6H); 1.71 (d,

2H); 1.28 (s, 18H); 1.18 (s, 18H). 13C NMR 6 160.49; 156.44; 151.26; 138.74; 137.58;

136.90; 134.04; 132.91; 130.16; 129.61; 128.60; 128.41; 128.06; 125.91; 125.08; 120.64;









72.62; 38.86; 34.89; 30.05; 28.99; 24.47; 21.47; 20.23. Anal. Calc. for C68H84N206Pd: C,

72.16; H, 7.48; N, 2.48. Found C, 72.03; H, 7.65; N, 2.51.

Synthesis of [2-2-F](Bu4N)

A portion of 0.050 g (0.046 mmol) of 1-Ni along with 0.029 g (0.092 mmol) tetrabutyl-

ammonium fluoride trihydrate was dissolved in 1 mL toluene. Crystals suitable for X-ray

diffraction were grown by a slow diffusion of pentane into toluene solution. 1H NMR: 6 7.44 (s,

2H); 7.16 (d, 2H); 6.86 (s, 4H); 6.83 (s, 2H); 6.75 (s, 4H); 6.37 (s, 2H); 3.37 (m, 8H); 3.14 (s,

2H); 2.46 (m, 2H); 2.17 (m, 6H); 2.13 (s, 12H); 1.92 (m, 2H); 1.68 (m, 8H); 1.46 (q, 8H);

1.30 (m, 2H); 1.12 (s, 18H); 1.10 (s, 18H); 1.02 (t, 12H). Anal. Calc. for C84H120N306NiF: C,

74.98; H, 8.99; N, 3.12. Found C, 74.24; H, 8.91; N, 2.64.

Determination of binding constants (LogKs)

A 4.61 x 10-M solution of 2-2 in acetone was titrated with 23 tL aliquots of a tetra-

butylammonium fluoride solution. Absorbance was plotted versus fluoride concentration at 450

nm and a non-linear least squares regression was then run on the data using the following

equation:59 X = Xo + [(Xim Xo) / 2co] [co + cm +1/Ks [(co + cM + 1/Ks)2 4cocM]1/2]. By

solving this equation for Ks we were able to obtain logKs of 5.64 for 1-Ni(II) and 5.81 for 2-3.










Table 2-1. X-ray data for the crystal structures of 2-1 and the complexes R,R-2-1, 2-3, and 2-2-F.

2-1-CH3CN R,R-2-2-CH3CN 2-3-Et20 2-2-F-Et20


total reflections
unique reflections
0maxo
empirical formula
M,
crystal system
space group
a (A)
b(A)
c (A)
a (0)

y(o)
Vc (A3)
Dc (g cm-3)
Z
j(Mo-Ka) (mm-1)
R1 [I > 2c(7) data]b
wR2 (all data)c
GoF


16607
10576
25
C70 H89 N3 06
1068.44
triclinic
P-1
13.8245(12)
14.1393(12)
17.9268(15)
70.554(2)
89.380(2)
71.177(2)
3109.2(5)
1.141
2
0.072
0.0907
0.1629
0.946


18198
14424
28
C72 H90 N4 06 Ni
1166.19
triclinic
P1
13.1800(9)
13.7606(10)
20.2871(14)
83.2670(10)
77.1700(10)
66.1000(10)
3278.4(4)
1.181
2
0.349
0.0506
0.1179
1.019


40023
26428
28
C70H89 N2 07 Pd
1176.86
triclinic
P-1
16.6011(11)
21.7001(15)
23.4994(16)
71.3800(10)
86.2890(10)
71.1520(10)
7585.3(9)
1.031
4
0.289
0.0584
0.1230
0.821


29805
19898
28
C88 H130 F N3 07 Ni
1419.66
triclinic
P-1
13.7248(9)
17.0299(11)
22.1543(14)
71.4080(10)
89.0850(10)
72.8510(10)
4672.3(5)
1.009
2
0.257
0.0608
0.1687
0.968


0 1356
F357 O 135

NH HN


Y445 H
O/


H-0
S-107


Figure 2-1. Schematic diagram of the open conformation of CIC chloride channel. Chloride is
held in place by two OH-C1 hydrogen bonds from Y445 and S107.










HO


HO


OHR
R- ,


R = t-bu
"all up"


Figure 2-2. Triphenoxymethane platform with the phenols in the "all up" position relative to the
methine carbon hydrogen.




HO H \ H N N
H, OH I HO


R = t-bu
"all up"


Bu4NF


\ 2-2,2-3
[M(II)-F] R omitted for clarity


Figure 2-3. Procedure used for the synthesis of 2-1, macrocycle metalation to form 2-2, and 2-3
and fluoride binding.
































Figure 2-4. Depiction of the solid-state structure of 2-1 (30% probability ellipsoids for nitrogen
and oxygen, carbons drawn with arbitrary radii)


































Figure 2-5. Depiction of the solid-state structure of 2-2 (30% probability ellipsoids for nitrogen,
oxygen and nickel, carbons drawn with arbitrary radii)





























Figure 2-6. Depiction of the solid-state structures of 2-3 (30% probability ellipsoids for nitrogen,
oxygen and palladium, carbons drawn with arbitrary radii)










1-Pd(ll)


Figure 2-7. H NMR spectrum of 2-3 (top) and [2-3-F]1- (bottom) taken in d6-DMSO with an
inset of the 19F NMR spectrum of [2-3-F]1- in the region of bound fluoride.


I *


I


7.8 7.4


7.0 6.6 6.2 ppm

7.0 6.6 6.2 ppm


Figure 2-8. 1H NMR spectrum of 2-2 with a sharp and well defined aromatic region.





























7.8 7.4 7.0


Figure 2-9. 1H NMR spectrum of 2-2 with 0.5 equivalents of fluoride added.


pI
I l I I





7.8 7.4 7.0 6.6 6.2 ppm

Figure 2-10. H NMR spectrum of 2-2 with one equivalent or more of fluoride.


6.6 6.2 ppm










8000


6000


1 eq. F-


4000


2000



0
350 375 400 425 450 475 500 525 550
Wavelength (nm)

Figure 2-11. UV-Vis titration of 2-2 (4.61x10-5 M) with tetra-butylammonium fluoride in
acetone. Titration was complete after the addition of a single equivalent of fluoride.
Inset shows the change in color upon anion coordination from bright red to dark
green.


0.6


S0.4

S0.3

0.2

0.1

0


0.2 0.4 0.6 0.8 1
[L] / ([L] + [A])


Figure 2-12. Job plot shows the titration of 2-2 with tetrabutylammonium fluoride. Apex at 0.5
indicates a 1:1 binding mode of anion to receptor. [L] = concentration of receptor;
[A] = concentration of anion; A = absorbance.













0.35 *

0.3

0.25

A 0.2

0.15

0.1

0.05

0
0 0.5 1 1.5 2 2.5

Equivalents of Fluoride


Figure 2-13. Absorbance plotted versus concentration of fluoride for the titration of 2-2 at
450nm with tetrabutylammonium fluoride. The data points represent experimental
values and solid line represents the fit to the data.






























Figure 2-14 Crystal structure of [2-2-F]1- with fluoride bound in the phenolic pocket. The
tetrabutylammonium cation, solvates, and hydrogens have been omitted for clarity.
Selected distances: (a) C(15)...C(46) 5.28 A; O(1)...O(3) 2.697(7) A; 0(4)...0(5)
2.784(8) A (b) C(15)*..C(46) 5.73A; O(2)*..F(1) 2.539(2) A; O(3)*..F(1) 2.509(2) A;
O(5)*..F(1) 3.098(3) A; O(6)*..F(1) 2.573(2) A.










10000


8000


6000


4000


2000


0
350 375 400 425 450 475 500 525 550
Wavelength


Figure 2-15. UV-Vis titration of 2-3 salen (4.61x10.5 M) with tetra-butylammonium fluoride in
acetone. Titration was complete after the addition of a single equivalent of fluoride.




0.5


0.3

S0.2

0.1

0
0 0.2


0.4 0.6 0.8
[L] / ([L] + [A])


Figure 2-16. Job plot from UV-Vis spectra titration data of 2-3 in acetone with tetra-
butyammonium fluoride















0.5


0.4


A 0.3


0.2


0.1


0
0 0.5 1 1.5 2 2.5

Equivalents of Fluoride

Figure 2-17. Absorbance plotted versus concentration of fluoride for the titration of 2-3 complex
at 450 nm with tetrabutylammonium fluoride. The data points represent experimental
values and solid line represents the calculated values.









CHAPTER 3
A SYNTHETIC MODEL OF THE CLC CHLORIDE ION CHANNEL; A STRUCTURAL
AND ANION BINDING STUDY

Introduction

In nature, the C1C chloride channel selectively transfers chloride ions across membranes,

and with the recent elucidation of the structure by MacKinnon and coworkers, a clear picture of

the halide binding site is now available.47 At one point in the transfer process, chloride is held by

hydrogen bonds to four amino acid residues. Amide nitrogrens from Ile 356 and Phe 357

provide two hydrogen bonds while the hydroxide groups on Ser 107 and Tyr 445 provide the

remaining stabilizing interactions. In this instance, nature employs a mixture of N-H and O-H

donors for the transportation of halides, but surprisingly, the scientific community has primarily

focused their efforts on the use of N-H groups such as amides, amines, pyrroles, and ureas to

provide the hydrogen bonding interactions for artificial anion receptors.22 The utility of O-H

groups in anion receptors has been quite limited with only a handful of examples reported in the

literature.50

Recently, we demonstrated that four phenols could be carefully positioned to produce a

selective and efficient receptor for the fluoride anion.63 In this system, the phenolic groups were

tethered to a salen macrocycle, and metal complexation helps to orient the four groups into a

pocket via hydrogen bonding and steric interactions. The metal macrocycle receptor offered

other advantages such as the capacity to modulate the size of the halide binding pocket and the

ability to monitor the binding event through spectral changes in the intense MLCT transitions.

In view of the proclivity for 2-1 to bind selectively fluoride and the mixed N-H and O-H

binding site found in the C1C channel, we set out to prepare a structural model of the C1C

channel with a mixture of two N-H and two O-H donors attached to the salen backbone. Herein,









we report the synthesis and study of a CIC channel model complex with a focus on its structural

and anion binding properties.

Results and Discussion

For the design of artificial anion receptors, the salen macrocycle offers many advantages.

The ligands are easily prepared via a simple Schiff base condensation of salicylaldehyde and a

diamine, and a range of donor groups adept at binding to both cationic and anionic groups can be

attached to the salicylaldehyde moiety with little synthetic effort. Incorporation of a metal center

into the macrocyclic rings affords a rigid framework, and if the donor groups are properly placed

in the periphery of the salicylaldehyde, a tight binding pocket can be produced at the cleft

between the two sides of the macrocycle. The size of the binding site can be modulated by

changing the identity and radii of the metal center within the macrocycle, and since metal salen

compounds normally exhibit MLCT transitions in the visible region, the binding event can often

be followed by monitoring the position of this intense absorption band.

Salens as Anion Receptors

Reinhoudt and coworkers were the first to utilize metal sales for anion binding.39 Their

strategy focused on using acetoamido groups tethered to the salen phenoxide groups to act as

hydrogen bond donors to a phosphate anion, while uranyl was incorporated into the macrocycle

to provide hydrogen bonding acceptor site for the phosphate proton. Salens can also act as

receptors for Ni(II) and Cu(II) sulfate when amine groups are bound at the periphery of the

macrocycle.52

We have recently demonstrated that four phenols tethered to a salen backbone in a pseudo

tetrahedral arrangement creates an efficient and selective fluoride sensor. Initial work with 2-1

focused on the diamagnetic and square planar metals Ni(II) and Pd(II) which afforded the

opportunity to monitor the receptor synthesis and the anion binding event by NMR spectroscopy.









Each molecule was structurally characterized and the difference in metal radii had an impact on

the size of the binding cavity as well as an influence of the binding constants for fluoride.

Binding properties of these complexes were tested with n-Bu4N+ halide salts in a variety of

solvents. The intense MLCT absorptions (F 7400) offered by both 2-2 and 2-3 offer a

convenient way to monitor the fluoride binding event. Addition of fluoride to these receptors

causes a dramatic red shift in the absorption spectrum with two distinct isobestic points

indicating a single species forms in solution. The logKs values were determined to be 5.6 for 2-2

and 5.8 for 2-3 in acetone and were 5.8 for both complexes in DMSO. Both 2-2 and 2-3 only

reacted with fluoride. Steric constraints in the binding cavity precluded the binding ability of

larger halides C1, Br, and F. Upon addition of large excesses of the larger anions no changes

were detected in the 1H NMR spectrum or the UV-Vis spectra.

Synthesis of a Mixed Salen Receptor

With the ability to incorporate O-H donors into an anion receptor system, we envisioned

a synthetic mimic of the C1C chloride channel could be created, but this would also require two

amide type N-H's to replicate the donors from Ser 107 and Tyr 445. The salen macrocycle can

be used as a way to organize groups for anion binding, and mixed salen systems that involve two

different moieties have been reported in high yields. However, to employ this method a

molecule with N-H donor groups that could be incorporated into a salen system had to be

developed.64

In our group, Melanie Veige isolated a urea substituted salicylaldehyde and this group can

be incorporated into a salen macrocycle (Figure 3-4). The resulting macrocycle would provide

two N-H donors from the urea group.65 Urea groups are a common motif in synthetic anion

receptor systems and have shown the ability to coordinate a range of anions including the target

chloride ion.66 The two N-H groups from the urea are separated by a carbonyl creating an









environment that is similar to the backbone of the protein. Both N-H's are also aligned in the

same direction which is critical to the receptor for anion coordination.

While mixed salen systems have previously been reported, they have included only simple

salicylaldehydes,64 so the incorporation of highly functionalized groups would require modified

procedures to obtain the desired mixed salen products. With a combination of urea and the two

phenolic groups onto a single platform, the molecule could serve as a model of the C1C channel

with two O-H and two N-H donors available for anion coordination. In order to synthesize a

mixed salen product, 1,2-diaminocyclohexane HC1 was prepared and the hydrochloride salt acts

as a protecting group to prevent further reactions at one of the amine positions. A stepwise series

of condensation reactions followed by metalation with Ni(II) (Figure 3-5) affords a product.

The choice of solvent, reaction time, temperature and purification methods are critically

important to the synthesis of this system. The isolation of (3-6) is readily attainable, but the

condensation of 3-6 and the urea compound 3-5 often leads to a mixture of products. The major

product formed is 2-1 as the imine bond of 3-6 breaks and a rearrangement of the molecule is

occurring. Rather than forming a compound with both the phenol group and urea groups, the

major products of the reaction were the bis-phenol and bis-urea compounds. Initial attempts for

the formation of 3-7 were performed in ethanol as most sales, including mixed salen systems,64

are typically carried out in this solvent. However, the isolation of the desired product was never

obtained in polar solvents. Compound 3-7 was synthesized by a reaction in methylene chloride

at room temperature. The isolation of the pure product was never obtained, as column

chromatography of salen molecules can lead to decomposition due to the high sensitivity of the

imine bonds. Metal salen compounds are usually more stable than the uncoordinated ligand, and









upon the metalation of 3-7 with Ni (II) a more rigid compound (3-8) was easily purified with an

overall yield of 20%.

Anion Coordination and Binding Constants

The anion binding properties of this system were tested by the addition of tetra-butyl-

ammonium halide salts to solutions of the receptor. Compound 3-8 was able to bind fluoride and

chloride while having no interaction with the larger bromide anion. A distinct red shift in the

strong MLCT absorptions is detected upon anion complexation for both fluoride and chloride

with the main absorption peaks of the spectrum shifting from 411 nm to 428 nm for fluoride and

from 411 nm to 421 nm for chloride. The addition of a large excess of bromide to the solution

causes no changes to either the UV-Vis or NMR spectra.

The binding constants (Ks) were determined from the data obtained by UV-Vis

spectroscopy anion titrations. The measured absorbance were plotted as a function of fluoride

ion concentration of the solution at 450nm and a non-linear least squares regression was used to

determine binding constants with the equation:59 X = Xo + [(Xim Xo) / 2co] [co + cm +1/Ks -

[(co + cm + 1/Ks)2 4cocm]1/2]. In this equation, X is the measured absorbance, Xo is the initial

absorbance, Xlim is the limiting absorbance, co is concentration of anion in solution, cm is the

concentration of the receptor, and Ks is the binding constant. A program to perform a non-linear

least squares regression on the data60 which minimizes the error of each data point to fit the

standard equation by altering Ks was written in excel. The value of Ks that leads to the lowest

sum of errors is the binding constant for the system. Binding constants for 3-8 were determined

to be Log Ks = 8.3 for fluoride and Log Ks = 1.74 for chloride. The coordination of fluoride

occurs readily as seen by its extremely high binding constant. Although chloride does coordinate

to the receptor, it is less favorable. The larger size of chloride as well as its lower charge density









led to the smaller interactions. Compound 3-8 fully coordinates fluoride upon addition of- 1

equivalent of anion while it takes 30 equivalents of chloride to fully titrate the receptor.

Solid State Structure

Upon addition of excess chloride ion, 3-8 binds the anion and single crystals of the

complex with chloride coordinated were obtained. In the solid state (Figure 3-7), chloride is held

in the cavity by four rather strong hydrogen bonds (chloride oxygen distances of 3.158(3) A and

3.108(4); chloride nitrogen distances of 3.512(4) A and 3.183(4)). There is a slight distortion of

the urea group and the phenols in order for the receptor to accommodate the chloride ion. These

small structural changes to the receptor, which are caused by anion coordination, have also been

observed for 2-1 upon binding fluoride.

Conclusions

A synthetic model of a C1C chloride channel has been designed and developed. The

incorporation of phenolic and urea subunits onto a salen macrocycle platform has created a

highly functionalized mixed salen system which is able to coordinate chloride in a similar

manner as seen in receptors found in nature. A solid-state structure of 3-8 with a chloride anion

bound has been obtained and it shows the binding mode with chloride interacting with all four

hydrogen bond donors in the system. The structure is the first example of a synthetic chloride

receptor that involves the same hydrogen bonding interactions as the C1C chloride ion channel.

The positioning of the donor group to form a cavity of a specific size are important to the anion

binding event as the receptor can easily accommodate fluoride and chloride while there are no

interactions with larger anions such as bromide.

Binding constants for the receptor system have been obtained and follow the expected

selectivity trend with a greater preference for the smaller anions. The metalated salen

macrocycle serves multiple purposes, as a rigidifying structural component and also it enables









the binding constants to be monitored by UV-Vis spectroscopy due to strong MLCT transitions.

The receptor has a high binding constant for fluoride of log Ks = 8.3 and a much lower log Ks =

1.74 for chloride. There is no evidence that the larger bromide anion interacts with the receptor.

Experimental Methods

General Considerations.

1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at

299.95 and 75.47 MHz for the proton and carbon channels. UV-Vis spectra were recorded on a

Varian Cary 50 spectrometer. Elemental analyses were performed at either the in-house facility

of the Department of Chemistry and the University of Florida. All solvents were ACS or HPLC

grade and used as purchased except for metalation reactions where the solvents were dried with a

Meyer distillation system prior to use. Melanie Veige was responsible for the synthesis of

compounds 3-1 through 3-5.

Determination of binding constants (LogKs)

A solution of receptor in acetone was titrated with aliquots of a tetra-butylammonium

halide solution. Absorbance was plotted versus fluoride concentration at 450 nm and a non-

linear least squares regression was then run on the data using the following equation:59 X = Xo +

[(Xiim Xo) / 2co] [co + cm +1/Ks [(co + CM + 1/Ks)2 4coCM]1/2]. Solving this equation for Ks

gives the binding costant. Job plots we obtained by measuring the absorbance of a series of

solutions with different proportion of receptor and anion and indicate a 1:1 ratio.

Synthesis of 3-1

A solution of 5-tert-butyl-2-hydroxybenzaldehyde (60.0 g, 337 mmol) in glacial acetic acid

(240 mL) was cooled in an ice bath. Fuming nitric acid (15.3 mL, 1 equiv., 337 mmol) was

slowly added via addition funnel. After 15 min of stirring, the ice bath was removed and the

solution was stirred at ambient temperature for 90 min. The ice bath was reapplied intermittently









to prevent the internal reaction temperature from exceeding ca. 45 C. The reaction mixture was

poured onto crushed ice (800 mL). The yellow precipitate thus formed was filtered and washed

with water, then recrystallized from abs. EtOH/H2O to give 3-1 as a yellow crystalline solid

(68.7 g, 91%). The compound was used without further purification. An analytically pure

sample was obtained by further purification by column chromatography (pentane-ether 3:1). H

NMR (DMSO-d6): 6 11.34 (bs s, OH), 10.28 (s, CHO), 8.20 (d, J=2.4 Hz, Ar-H), 8.07 (d, J=2.4

Hz, Ar-H), 1.30 (s, 9H). 13C NMR (DMSO-d6): 6 191.5, 151.8, 142.3, 137.6, 132.6, 127.7,

124.9, 34.2, 30.6. HRMS (El): Theoretical 223.0845; Measured 223.0837. Anal. Calc. for

CliH13NO4; C, 59.46; H, 5.97; N, 6.22. Found C, 59.19; H, 5.87; N, 6.27.

Synthesis of 3-2

To a solution of 3-1 (53.3 g, 239 mmol) in CHC13 (350 mL) was added 1,3-propanedithiol

(24 mL, 1 equiv.). The mixture was stirred at ambient temperature for 60 min. then was cooled

in an ice bath. To the cold mixture was added BF3OEt2 (3 mL, 0.1 equiv., 23.9 mmol). The

mixture was stirred 16 h with gradual warming to ambient temperature. The reaction mixture

was transferred to a separatory funnel, diluted with CHC13 (250 mL), and washed successively

with H20 (3x100 mL) and brine (150 mL). The volatiles were removed in vacuo and EtOH (250

mL) was added to the residue. The slurry was stirred at ambient temperature for 1 h, then cooled

in an ice bath for 30 min. The mixture was filtered and the collected solids were washed with

cold EtOH. 3-2 was obtained as a bright yellow crystalline solid (65 g, 87 %). An analytically

pure sample was obtained via further purification by column chromatography (pentane-ether

4:1). H NMR (DMSO-d6): 6 10.64 (br s, OH), 7.86 (d, J=2.4 Hz, Ar-H), 7.79 (d, J=2.4 Hz, Ar-

H), 5.73 (s, dithiane-H), 3.19-3.11 (m, 2H), 2.94-2.29 (m, 2H), 2.21-2.15 (m, 1H), 1.82-1.69 (m,

1H), 1.27 (s, 9H). 13C NMR (DMSO-d6): 6 146.8, 142.3, 135.7, 132.3, 130.0, 120.9, 42.3, 34.0,









31.2, 30.7, 24.6. HRMS (EI): Theoretical 313.0806, measured 313.0820. Anal. Calc. for

C14H19N03S2: C, 53.99; H, 6.24; N, 4.42. Found C, 53.65; H, 6.11; N, 4.47.

Synthesis 3-3

To a mixture of 3-2 (46.7 g, 149 mmol) in EtOH (475 mL) and AcOH (475 mL) was added

Fe powder (33.3 g, 4 equiv., 597 mmol). The mixture was heated to reflux under a nitrogen

atmosphere. The mixture gradually became a very dark solution, and after approximately 1 h

copious solids precipitated. After 1 h at reflux TLC indicated completion of the reaction. The

mixture was concentrated in vacuo and EtOAc (300 mL) and H20 (300 mL) were added.

Saturated K2CO3 was added to neutralize the aqueous layer. The aqueous layer was extracted

with additional EtOAc (3x65 mL). The combined organic fractions were washed with brine,

dried over MgSO4 and filtered. The solution was transferred into a round-bottomed flask

equipped with a stir bar. HC1 in dioxane (4N, 75 mL, 300 mmol, 2 equiv.) was added slowly via

addition funnel. The mixture was stirred at ambient temperature for 3 h, then transferred to a -20

C freezer for 16 h. The mixture was filtered cold, and the collected solids washed with cold

EtOAc to provide the HC1 salt of 3-3 as a beige powder. The mother liquors were concentrated

to approximately 200 mL and cooled to obtain a second crop of product. A total of 43.1 g (90%)

of the HC1 salt of 3-3 was obtained. Salt 3-3 (22.6 g, 70.8 mmol) was charged into a round-

bottomed flask with CH2C12 (150 mL) and H20 (150 mL) containing K2CO3 (20.0 g, 2 equiv.,

142 mmol). The mixture was stirred at ambient temperature for 2 h. The organic phase was

removed and the aqueous layer was extracted with additional CH2C12 (2x30 mL). The combined

organic were washed with brine, dried over MgSO4, filtered and concentrated to a small

volume. Pentane was added slowly to precipitate the free amine 5 (17.3 g, 86% from the salt) as

a beige solid. 1H NMR (CDC13): 6 6.74 (d, J=2.4 Hz, Ar-H), 6.63 (d, J=2.4 Hz, Ar-H), 6.45 (br

s, ArOH), 5.30 (s, dithiane-H), 3.74 (br s, ArNH2), 3.11-3.01 (m, 2H), 2.95-2.88 (m, 2H), 2.24-









2.14 (m, 1H), 2.01-1.86 (m, 1H), 1.25 (s, 9H). 13C NMR (CDC13): 6 143.9, 140.9, 135.7, 122.4,

115.6, 114.3, 48.2, 34.3, 31.7, 31.6, 25.1. HRMS (El): Theoretical 283.1065, Measured

283.1083. Anal. Calc. for C14H21NOS2: C, 59.55; H, 7.70; N, 4.97. Found C, 59.32; H, 7.47;

N, 4.94.

Synthesis of 3-4

To a solution of amine 3-3 (12.64 g, 44.7 mmol) in CHC13 (125 mL) was added

phenylisocyanate (4.85 mL, 1 equiv., 44.7 mmol). The solution was heated at reflux for 20 h,

then cooled to ambient temperature. The solution was concentrated to approximately 1/3 the

volume, and hexane was slowly added with stirring. The off-white precipitate 3-4 (17.0 g, 95%)

was filtered and washed with hexane. H NMR (DMSO-d6): 6 9.26 and 9.24 (overlapping s,

2H), 8.34 (s, 1H), 7.80 (d, J=2.4 Hz, 1H), 7.45 (d, J=8.7 Hz, 2H), 7.28 (t, J=7.8 Hz, 2H), 7.09 (d,

J=2.4 Hz, 1H), 6.99-6.95 (m, 1H), 5.70 (s, 1H), 3.12-3.04 (m, 2H), 2.90-2.86 (m, 2H), 2.15-2.10

(m, 1H), 1.80-1.69 (m, 1H), 1.23 (s, 9H). 13C NMR (DMSO-d6): 153.3, 142.4, 140.2, 139.6,

128.8, 128.4, 126.4, 121.9, 118.7, 118.2, 117.1, 44.1, 33.9, 31.5, 31.3, 24.8. Anal. Calc. for

C21H26N202S2: C, 62.25; H, 6.91; N, 6.66. Found C, 62.65; H, 6.51; N, 6.96.

Synthesis of 3-5

To a mixture of 3-4 (9.0 g, 22.4 mmol) in AcOH (400 mL) was added SeO2 (12.4 g, 5

equiv., 112 mmol). The resulting mixture was stirred at ambient temperature for 90 min during

which time 3-4 was fully dissolved and a byproduct precipitated. The mixture was filtered

through a pad of Celite. The filter cake was washed with AcOH, and the filtrate was

concentrated in vacuo to a solid. To the solid was added EtOAc and H20, and the aqueous layer

was basified with saturated K2CO3. The biphasic mixture was filtered again through Celite and

the filtrate was transferred to a separatory funnel. The aqueous layer was extracted with EtOAc.

The combined organic were washed with brine, dried (MgSO4), filtered and concentrated to a









slurry. Hexane was added and the yellow-orange precipitate (6.5 g, 93%) was filtered and

washed with hexanes. The solid could be recrystallized from MeOH/H2O. An analytically pure

sample was obtained by column chromatography (pentane-ether 4:1) however the urea was used

without further purification. H NMR (acetone-d6): 6 11.34 (br s, OH), 9.98 (d, J=0.9 Hz, CHO),

8.77-8.74 (m, 2H), 7.93 (br s, 1H), 7.57-7.54 (m, 2H), 7.43-7.42 (m, 1H), 7.31-7.25 (m, 2H),

7.02-6.96 (m, 1H), 1.34 (s, 9H). 1C NMR (acetone-d6): 6 198.6, 153.3, 148.5, 143.5, 140.6,

129.5, 129.1, 124.1, 123.0, 120.3, 119.3, 34.9, 31.5. HRMS (ESI-FT-ICR-MS) for [2M+Na]+

Theoretical 647.2840, Measured 647.2852; theoretical for [M+Na] 335.1366, measured

335.1372. Anal. calc. for C18H20N203: C, 68.84; H, 6.68; N, 8.71. Found C, 69.21; H, 6.45; N,

8.97.

Synthesis of 3-6

A portion of 1.0 g (6.66 mmol) 1,2-diaminocyclohexane HC1 was dissolved in 50 mL

methanol. After dissolving 50 mL ethanol was added along with 3.0 g (6.33 mmol) of 3-(2,2'-

Methylenebis (4-methyl-6-tert-butylphenol)-5-methyl-2-hydroxybenzaldehyde. The reaction

mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the

solid was washed with water, filtered and dried. The solid was dissolved in dry ether and a pale

yellow solid precipitated which was filtered and dried to afford the product in an 82% yield (3.1

g). 1H NMR. 6 8.48 (s, 1H); 7.03 (s, 2H); 6.99 (s, 1H); 6.83 (s, 1H); 6.61 (s, 2H); 6.50 (s, 1H);

6.01 (s, 1H); 5.42 (bs, 2H); 5.09 (bs, 1H); 3.28 (m, 1H); 2.75 (m, 1H); 2.19 (s, 9H); 1.71(m,

4H); 1.38 (s, 9H); 1.35(s, 9H). 13C NMR 167.6; 157.41; 151.12; 150.64; 137.42; 137.20;

133.78; 130.62; 128.61; 127.48; 126.95; 126.53; 118.45; 70.01; 55.76; 38.16; 34.86;

34.64; 33.00; 29.93; 28.47; 23.78; 23.27; 21.19; 20.83. HRMS: Theoretical 571.3894;

Measured 571.3894 [M -C1].









Synthesis of 3-7

A portion of 0.826 g (1.36 mmol) 3-6 was dissolved in 75 mL methylene chloride. To this

solution was added 0.38 mL (2.72 mmol) of triethylamine and 0.425 g (1.36 mmol) of 3-5 The

reaction mixture was stirred overnight at room temperature. The solution was poured into a

separatory funnel and washed with a 1 M HC1 solution and then with water. The solution was

dried with sodium sulfate and the solvent was removed. No attempt at further purification was

made and the resulting crude product was used as the starting material in the synthesis of 3-8.

Purification was performed after metalation of the complex.

Synthesis of 3-8

A portion of 0.80 g 3-7 was dissolved in 100 mL of dry THF. To this solution was added

0.23 g nickel acetate and the reaction was stirred at room temperature for 2 hours. The solvent

was removed under vacuum and the product was dissolved in pentane and filtered. The solvent

was removed from the filtrate leaving a yellow / orange solid. The solid was then washed with

an excess of methanol yielding 0.200g of pure product (24% for two steps). 1H NMR: 6 8.62 (s,

1H); 8.33 (d, 1H); 7.03 (m, 12H); 6.90 (d,, J= 6.6 Hz, 1H); 6.87 (s, 2H); 6.60 (s, 2H); 6.29 (s,

1H); 3.70 (bs, 1H); 3.29 (bs, 1H); 2.27 (s, 3H); 2.26 (s, 3H); 2.18 (s, 3H); 1.36 (s, 9H); 1.33 (s,

9H); 1.28 (s, 9H). 13C NMR 6 158.13; 157.94; 157.26; 152.58; 151.30; 150.67; 150.57;

138.86; 138.76; 138.55; 138.25; 135.38; 131.91; 130.87; 130.75; 130.40 130.33; 129.71;

129.11; 128.63; 127.22; 126.91; 126.52; 124.90; 122.25; 120.42; 119.94; 119.74; 119.08;

117.48; 70.79; 36.88; 34.82; 34.60; 34.19; 31.42; 30.02; 29.92; 29.45; 28.33; 28.14;

23.99; 21.29; 21.20. HRMS: Theoretical 921.4459; Measured 921.4487 [M + H+]. Anal. Calc.

for C55H66N405Ni: C, 71.66; H, 7.22; N, 6.08. Found C, 71.44; H, 7.58; N, 5.79.









F357 o 1356

NH H N H '-



Y445 H 'H-O
^^0 ^S~o


Figure 3-1. Schematic diagram of the open conformation of CIC chloride channel. Chloride is
held in place by two OH-C1 hydrogen bonds from Y445 and S107.






/Ni -
\-/ 0 0o
H H


OH HO

[2-2-Fl

Figure 3-2. Schematic diagram of [2-2-F]-; a fluoride is hydrogen bonding with the four phenols
of the anion receptor.































Figure 3-3. Structure of salen based anion receptor with amine groups at the periphery. The
receptor coordinates both cations and anions


HS/\/\SH


HNO3

AcOH


BF3 OEt2


O OH
3H H





3-5


SeO2


-NO2 S -

1. Fe, HAc
2. HCI
3. K2CO3

3-3
PhNC



OH





3-4


Figure 3-4. Synthetic scheme for compound 3-5.


O OH

N











NH3Cl


R = t-bu
"all up"


H2N NH3CI


N Et3


Ni(OAc)2
<^ ----


R 3-8


Bu4NCI

uN N

/Ni\ 0 I

-\ HN

R 2-NH HN

R 2-Ni(II) -


Figure 3-5. Synthetic scheme for the synthesis of mixed phenolic-urea salen system (3-7),
metalation at salen binding site and anion coordination (3-8).










6000


5000

4000

F 3000

2000

1000

0
330 380 430 480 530
Wavelength nm


Figure 3-6. Titration plot of 3-7 with fluoride in acetone. There is a dramatic red shift in the
absorption spectrum and also two well defined isobestic points.

































Figure 3-7. Depiction of the solid-state structure (30% probability ellipsoids, carbons drawn
with arbitrary radii) of [3-8-C1]- with chloride hydrogen bound to two phenols and
two N-H's from the urea. The tetrabutylammonium cation and carbon hydrogens
have been omitted for clarity. Selected distances: O(2)*..Cl(1) 3.158 A;
O(3)...CL(1) 3.108 A; N(3)...Cl(1) 3.512 A, N(4)...Cl(1) 3.183









CHAPTER 4
METAL SALEN UREA COMPLEXES AND THEIR HIGH AFFINITIES FOR THE HALIDES

Introduction

The use of N-H groups as hydrogen bond donors is commonly employed in synthetic

anion receptors1 as virtually all reported receptors focus on ligands incorporating groups such as

amides, amines, pyrroles, and ureas.22 The urea group is among the most popular binding motifs

in synthetic anion receptors since it offers two hydrogen bond donor groups aligned in the same

direction, which are also the appropriate distance from one other to have strong interactions with

a variety of anions including fluoride, acetate, and phosphate among others.67 The synthetic ease

in which ureas can be prepared also accounts for much of their diversity in a multitude of

receptor systems (figure 4-1)48

Anion Receptor Systems Incorporating Ureas. Urea groups have been incorporated into

multiple macrocyclic systems where molecular flexibility and cycle size impacts the anion

binding affinity.69 Ureas have also been attached to various platforms in order to preorganize

multiple urea groups.70 Preorganization of multiple ureas can lead to stronger hydrogen bonding

than a single moiety as well as a potential increase in selectivity. Since ureas have two donors

aligned in the same direction, arranging multiple groups in a manner to create a cavity affords

the opportunity to have a high number of possible hydrogen bonding sites. Ureas have also been

seen to adopt different geometries depending on the anion that it binds, making them versatile.7

For the development of anion receptors, it would seem that thiourea groups would be a

better candidate because it is more acidic (pKa of 21.1) than urea (pKa of 26.9).72 Thioureas

also have the advantage that they do not self associate as is often seen with ureas.73 Self

association occurs when the N-H groups are hydrogen bonding to the carbonyl of another urea

thus it is unavailable for anion coordination. Thioureas tend however, to deprotonate in the









presence of most anions preventing their use as an effective receptor.74 In contrast ureas require

a large excess of fluoride and using designed synthesis can prevent self associating from

occurring.75

Metals have been used as a way to assemble urea groups for hydrogen bonding.76 The

binding site can be regulated by the size and geometrical preferences of the metal as well as the

nature of the hydrogen bond donor substituent. The coordination of two ligands seen in figure 4-

2, coordinate around a Cu2+ ion which then sets the position of the urea groups. The four N-H's

form a binding site that is the appropriate size for the coordination of chloride. Binding

constants were determined by UV-Vis spectroscopy as the system offers strong absorption

measurements due to the conjugation of the ligand as well as the presence of a metal.

The salen complexes discussed in chapters two and three have shown to be effective

ways to induce anion coordination and the addition of metals into the systems modulates the size

of the binging cavity as well as offers a convenient way to monitor the binding event. Ureas are

among the best hydrogen bond donor groups and we envisioned creating a purely urea based

cavity attached to a metal salen backbone. Compound 3-8 has shown that ureas in combination

with phenols are selective for fluoride and chloride. The synthesis of a bis-urea receptor, its

interactions with various anions as well as the effects of metal coordination and regulation of the

size of the binding site are herein reported.

Results and Discussion

A simple Schiff base reaction with 1,2-diamino-cyclohexane and two equivalents of 3-5

affords compound 4-1. The two urea groups attached to the salen backbone have four N-H

donors (Figure 4-3), which are arranged into an anion binding cavity upon metalation with the

diamagnetic and square planar metals Ni (II) (4-2) and Pd (II) (4-3). Nickel and palladium

behave similarly yet differ in radius by about 0.15 A, affording the opportunity to regulate the









size of the binding cavity. The choice of metals allows the synthesis and the anion binding

properties of the receptor to be monitored by NMR spectroscopy. Metalation of 4-1 occurs at the

two salen imine nitrogens and the salen phenols but has no interaction with the urea N-H's.

Solid State Structures of Receptors. Both compound 4-2 and 4-3 were structurally

characterized and studied. For the nickel complex 4-2, two symmetry independent molecules

crystallized in the asymmetric unit and the structure is presented in figure 4-4. The average

distance of the four Ni-oxygen bonds in the two complexes (1.835 A) are typical for a Ni(II)

salen complex14 but significantly shorter than the corresponding average Pd-oxygen distances

(2.021 A). The subtle size difference between the two metals produces a profound increase in

the separation between the two urea groups which has many consequences for the structure and

anion binding ability of the two receptors.

The relatively small size of square planar Ni(II) forces a significant distortion within the

two arms. The phenyl rings on the urea, which would be expected to be coplanar due to the

conjugated nature of the system, have an angle of 85 between them, which is likely caused by a

steric clash between the phenyls. There is also a strong intramolecular hydrogen bond between

an N-H (N3) on one urea and the carbonyl (04) of the second urea of the system with a short N-

H-O distance of 2.190 A. The salen urea ligand system (4-1) is highly conjugated and thus

highly planar. In order to break the planarity and conjugation of the system, there is a high

energy cost to pay that will only occur under certain circumstances such as in compound 4-2

causing one of the urea arms to bend.

In contrast to compound 4-2, the Pd (II) compound 4-3 crystallizes with only one molecule

in the asymmetric unit and the distortions of the urea arms are no longer observed (Figure 4-5).

Since Pd (II) forms longer metal oxygen bonds than Ni (II) with a concomitant increase in









separation between the two extended arms. The ureas are oriented at a distance where the phenyl

rings are coplanar and the formation of an intramolecular hydrogen bond is less likely.

Compound 4-3 crystallized with a water molecule in the pocket which is hydrogen bound to all

four urea nitrogens at distances of 3.062 A, 3.155 A, 3.063 A, 3.248 A. The small size of water

allows it to lie within the plane of the urea molecule without causing distortions to the receptor

Anion binding properties of the two metal complexes were tested with n-Bu4N+ halide

salts in a variety of solvents including acetone and DMSO, and both 4-2 and 4-3 show a high

affinity for anions. As with compounds 2-2, 2-3 and 3-8 the binding constants of 4-2 and 4-3 for

anions can be monitored by UV-Vis spectroscopy. The absorbance spectrum of 4-2 shows two

strong MLCT transitions at 357 nm and 418 nm and the addition of fluoride to this solution

induces a red shift in the spectrum with the main absorbance peaks shifting to 361 nm and 427

nm respectively (Figure 4-5). There is also three well defined isobestic point in the titration plot

indicating a two state process.

There is a considerably smaller shift in the absorption spectra of 4-2 upon anion

coordination than was seen with compounds such as 2-2 which contained phenolic substituents.

The strongest absorbance of metal salen compounds is assigned to the MLCT transition.54 The

metal environments of compounds 2-2 and 2-3 are drastically altered by anion coordination. The

most important being the change in geometry of the four phenols which much distort to

accommodate the fluoride ion causing a distortion to the entire receptor including the salen

backbone. In both 2-2 and 2-3, there were intramolecular hydrogen bonds between the phenols

and the phenolates of the salen bound directly to the metal. The addition of fluoride to the

receptor disrupts the intramolecular hydrogen bonds of the phenols in order to coordinate to the

anion. The electronic environment of the metal is altered and this contributes to the shift in the









absorption spectrum. The colorimetric changes are less pronounced in 4-2 and 4-3 upon anion

coordination; however, the binding event could be still be monitored, allowing the binding

constant to be determined (Figure 4-6).

The data obtained from the titration of 4-2 with tetrabutylammonium fluoride affords the

binding constant Log Ks = 6.10, which is high and indicative of the strong interactions between

fluoride and the ureas. To determine this binding constant, the data from the titration was plotted

as a function of the equation: X = Xo + [(Xlim Xo) / 2co] [co + cm +1/Ks [(co + CM + 1/Ks)2

4cocM]1/2] and a non-linear least squares regression was performed to find the Ks value that best

fits the data (Figure 4-7).

While 4-2 has shown to have strong interactions with fluoride, the anion binding properties

of the receptor were tested with other larger anions, such as chloride and bromide. Both chloride

and bromide coordinate to this system with high binding constants and there is also a trend in

relative binding constants which is consistent with observations of the structures in the solid

state. The urea receptors have limited flexibility and the site of the binding cavity is determined

by the particular metals that are coordinated to the salen. The preference for a particular anion is

determined by geometry, size and the compatibility of the anion and receptor.

Compound 4-2 is able to coordinate chloride and this complex (4-4) has been structurally

characterized giving insight into the binding mode as well as the effect this has on the binding

constants (Figure 4-8). Size limitations of the binding cavity force the chloride to reside above

the plane of the molecule. The structure shows that all four urea nitrogens are hydrogen bonding

to the chloride at distances of N(3)*..Cl(1) 3.490 A; N(4)*..Cl(1) 3.255 A; N(5)*..Cl(1) 3.601 A;

N(6)*..Cl(1) 3.130 A.









The N-H groups are all slightly distorted and pointing towards the anion since chloride is

too large to be positioned any closer to the receptor. Each urea arm is splayed out as far as

possible in order to limit the amount of distortions that break the planarity and conjugation of the

molecule. The hydrogen bond distances from N(3) and N(5) are longer than the other two

nitrogens because they are directly connected to the rigid salen backbone and have limited

flexibility. The hydrogen bond distances from N(4) and N(6) to the chloride are significantly

shorter as the molecule is more flexible at this position and these two N-H's are able to twist and

point directly at the chloride.

The solid state structure shows the chloride ion sitting above the plane of the molecule and

directly adjacent to the anion is a highly disordered tetrabutylammonium cation. Packing plots

show that there is only one receptor bound to each anion in the solid state and Job plots indicate

a 1 : 1 complex in solution (Figure 4-9). Job plots are prepared by measuring differences in

absorption or chemical shifts of a series of solutions at various concentrations of anion and

receptor, and these changes are monitored by NMR and UV-Vis spectroscopy. Due to the large

changes in absorption spectra, UV-Vis spectroscopy was used for the creation of Job plots for 2-

2 and 2-3. For the urea based receptors however, the shifts in the N-H peaks were distinct and

the changes were monitored at different concentrations leading to a Job polt indicating there is a

one to one, receptor to anion binding mode.

The solid state structure of compound 4-2 with a bound bromide ion has been obtained

(Compound 4-5) and there are several structural differences to the receptor upon coordination of

bromide versus chloride. The larger size of bromide causes it to be positioned high above the

plane of the molecule and the hydrogen bond distances between the ureas and the bromide are

longer than those of 4-4 with distances of N(3)...Br(1) 3.616 A; N(4)...Br(1) 3.208 A;









N(5)*..Br(1) 3.576 A; N(6)*..Br(1) 3.358 A. The long receptor-bromide distances force

significant distortions in the planarity of the molecule. The distortion is not only seen in the urea

groups which must bend upwards to coordinate the bromide, but is also translated to the salen

backbone which has an 11.8 angle between the two nitrogen, oxygen, nickel planes [N(1), 0(1),

Ni(1) and N(2), 0(3), Ni(1)]. The structure also shows a disorder in the urea containing N(5),

N(6) and 0(4), with the receptor taking two slightly different angles as a means of coordinating

bromide. The receptor is trying to minimize the distortion caused as it is unfavorable to break

the receptors planarity and conjugation, but in order to coordinate bromide some distortions must

occur.

The addition of chloride or bromide to a solution of 4-2 leads to similar titration plots as

seen with fluoride with a red shift in the absorption spectra and three distinct isobestic points

(Figure 4-10). From the titration data, the binding constants were determined (Figure 4-11) and

there was a correlation between these constants and the hydrogen bond lengths. While 4-2 is a

strong receptor for both chloride (log Ks = 5.27) and bromide (log Ks = 4.29), there is an order of

magnitude difference in the binding constants. Chloride is able to form a more stable complex

with the 4-2 than with bromide because of its smaller size and ability to be positioned close to

the receptor.

While it is seen that the relative size of the anion plays an important role in the

coordination process, the spatial constraints of the receptor can be modified to make adjustments

to the anion coordination process. Compound 4-3 possesses a urea cleft that is larger than the

one in compound 4-2 which is caused by the incorporation of Pd (II). The binding mode of

chloride and bromide as seen in the solid states in compounds 4-4 and 4-5 indicate the anions is

positioned considerably above the plane of the molecule. Since 4-3 situates the two urea groups









further apart, it enables the anions to be positioned closer to the receptor and would possibly

have an effect on the binding constants.

To determine the anion binding properties of 4-3 NMR and UV-Vis spectra were taken.

The NMR spectrum showed distinct shifts in the positions of the urea N-H's upon addition of

fluoride, chloride and bromide. The UV-Vis spectra followed similar trends to that of 4-2. Upon

addition of various halides there was a red shift in the absorbance with two isobestic points. The

binding constants of 4-3 were determined with the UV-Vis titration data and were found to be

logKs = 6.09 for fluoride, logKs = 5.53 for chloride and logKs = 4.67 for bromide. There is

approximately an order of magnitude decrease in the binding efficiency of fluoride and chloride

and that of chloride and bromide.

The biding constants of both 4-2 and 4-3 decrease with an increase in anion size (Table 4-

1). Both receptors show similar binding constants for fluoride as it is the smallest anion tested

and spatial constraints would not be as significant of a factor. The binding constants for the

larger anions chloride and bromide are higher for receptor 4-3 than 4-2, consistent with the larger

separation of ureas allowing the anions to be positioned closer to the receptor. The ability to

adjust the size of the system by the incorporation of different metal centers into the salen

macrocycle creates a tunable system as which is demonstrated by the differences in binding

constant data for 4-2 and 4-3.

While the urea based salen receptors are very efficient halide binders, the addition of a

third urea arm could maximize the selectivity of the system for certain anions and still maintain

the high binding constants seen with 4-2 and 4-3. The addition of a third urea arm would create

a three dimensional pocket that would force the anion to be positioned inside the cavity. The

structure of the C3 symmetric receptor would have all three urea groups pointing inwards









preventing anions from residing above the plane of the molecule. Using a modified literature

procedure78 various salen type C3 symmetric ligands could be created with the tris-amine TREN

[Tris(2-aminoethyl)amine] and used to coordinate various lanthanides (Figure 4-13).

The initial work focused on the addition of lutetium to the tris-urea receptor because it is

a diamagnetic metal which allows the synthesis and anion binding properties to be followed by

1H NMR spectroscopy. Lutetium is the smallest of the lanthanides and coordination of different

larger metal centers could change the receptors size and binding properties, but a urea receptor

incorporating any other lanthanide was not isolated. A solid state structure of 4-6 was obtained

(Figure 4-14) and it shows the coordination mode of the metal center as well as the orientation of

the urea groups.

The structure shows that the Lu (III) is seven coordinate, bonding to the three imine

nitrogens and three phenolic oxygens as well as forming a bond with the apical nitrogen on tren

N(1). The coordination of lutetium sets the geometry of the ureas and forms a cavity that was

less flexible and more size selective for anions. The solid state structure shows an intramolecular

hydrogen bond between the proton on N(10) and 0(4) at a distance of 2.846 A as well as

hydrogen bond between N(3), N(4) and a water molecule.

Anion binding studies of 4-6 were done with various anions by both 1H NMR and UV-Vis

spectrum. There was no change in the NMR or UV-Vis spectrum with Br-, F, NO3-, C104

indicating no interaction with the receptor, but it was able to bind chloride. There was however a

change to the absorbance spectrum upon addition of chloride and a binding constant of logKs =

4.45 was determined in acetone. The addition of fluoride to 4-6 causes a demetalation of the

complex as noted by both the UV-Vis and 1H NMR spectral data. Demetalation of the complex









limits its ability to be used as an anion receptor and this phenomenon has been seen in previous

work in the group with other systems incorporating lanthanides.

To create a system that does not demetalate upon the addition of anions, an unreactive

metal center must be incorporated. Co (III) is an inert metal that should be extremely stable in

an octahedral environment. The tetra-amine tren used for the formation of 4-6 was ideal for the

coordination of large metals such as the lanthanides due to its size and ability to coordinate

through four nitrogens. To bind the smaller Co (III) the tris-amine tame [1,1,1-

tris(aminoethyl)methane] was used to coordinate first row transition metals because they prefer

to be six coordinate. The ligand synthesis and metalation of the system is summarized in Figure

4-15. For the metalation reaction, Co (II) acetate is the source of the metal and upon

coordination to the ligand it is oxidized to Co (III) with a dilute solution of peroxide. The

procedure for metalation must be followed as the direct addition of inert Co (III) to the ligand

would not be an effective means of metalation.

A solid state crystal structure was obtained for 4-8 which crystallized as a C3 symmetric

molecule (Figure 4-16). The Co (III) metal center is six coordinated and orientates the three urea

groups into a cavity with all six N-H's aligned in the same direction. There is a twist throughout

the entire molecule, from the imines to the ureas, as seen in the solid state structure, but the

configuration of the molecule is expected to be dynamic in solution. Differences in the lutetium

(4-6) and the cobalt (4-8) receptors are mainly a result of the size difference between the two

metals. The average Lu O bond is 2.168(8) A while the average Co -0 bond is 1.896(16) and

the difference is translated to the urea groups and the binding cavity.

The anion binding properties of 4-8 were test with n-Bu4N+ halide salts and the addition of

bromide and iodide to the receptor caused no changes in the UV-Vis or 1H NMR spectra









indicating that the addition of a third urea arm has placed size constraints on the binding cavity

and increased the selectivity of the urea system for smaller anions. Once again the coordination

of anions causes a red shift in the absorbance spectrum from which binding constants were

obtained. Binding constants of log Ks = 5.00 for fluoride in DMSO and log Ks = 4.95 in acetone

were determined, while chloride had a binding constant log Ks = 4.02 in acetone, but did not bind

in DMSO.

Conclusions

The incorporation of urea groups onto a metal salen macrocycle has shown to be an

efficient anion sensor. The urea groups have bound halides with high binding constants which

are directly proportional to the hydrogen bond lengths of the receptor to the anion. The receptors

formed 1 : 1 complexes with the anions as confirmed by both solid state and solution studies. By

changing the metal that is coordinated at the salen binding site, the receptor's binding ability can

be altered by changing the position of the urea groups. Besides structural considerations, the

metal's strong MLCT transitions and color also supply the means to monitor the binding of

anions by UV-Vis spectroscopy due to strong MLCT transitions and the color allow the binding

constants to be determined.

For compounds 4-2 and 4-3 anion coordination occurs at the periphery of the receptor as

the anion must be positioned above the plane of the molecule for an interaction to take place.

Adjustments to the size of the binding cavity can relegate the effectiveness in which coordination

occurs, but can not exclude the coordination of certain anions by spatial constraints. To increase

the selectivity of the system for certain anions, a third urea arm was added to the receptor. Using

Lu (III) as the metal template proved ineffective however, as demetalation occurred upon the

addition of certain anions. Instead, it was determined that Co (III) formed stable complexes with

a C3 symmetric ligand system and proved to be a selective binder of fluoride and chloride solely.









The biding constant of 4-6 is higher than that of 4-8 for chloride which may be a result of the

larger cavity that is formed as Lu (III) is larger than Co (III).

Experimental Methods

General Considerations

1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at

299.95 and 75.47 MHz for the proton and carbon channels. UV-Vis spectra were recorded on a

Varian Cary 50 spectrometer. All solvents were ACS or HPLC grade and used as purchased.

For the metalation reactions, the solvents were dried with a Meyer Solvent Purification system.

Some starting materials were synthesized by other members in the group. All NMR spectra are

taken in CDC13 unless otherwise stated. Some structures are not fully characterized and the

experimental procedures reflect known data obtained to date for these compounds. Tame was

synthesized by Priya Srinivasan, and 3-5 was synthesized by Melanie Veige.

Synthesis of 4-1

A 1.0 g portion (3.23 mmol) of 3-5 was dissolved in 50 mL of absolute ethanol. To this

solution was added 0.184 g (1.61 mmol) of trans-1,2-diaminocyclohexane. The reaction was

refluxed open to the air for 12 hours. The solution was cooled to room temperature and 50mL

water was added to the solution resulting in the precipitation of a bright orange solid. The solid

was filtered and dried to afford the product in 76% yield (0.86 g). 1H NMR: 6 9.36 (s, 2H); 8.51

(s, 2H); 8.29 (t, J= 2.7 Hz, 4H); 7.45 (s, 2H); 7.43 (s, 2H); 7.26 (t, J= 8.1 Hz, 6H); 6.95 (t, J=

7.5 Hz, 2H); 6.89 (d, J= 2.4 Hz, 2H); 3.54 (s, 2H); 2.02-1.40 (m, 8H); 1.20 (s, 9H). 13C NMR 6

165.7; 152.5; 151.8; 139.8; 139.0; 128.8; 128.5; 121.7; 119.8; 118.5; 118.0; 115.1; 68.8; 33.8;

32.1; 31.1; 23.5. HRMS: Theoretical 703.3966; Measured 703.4008.









Synthesis of 4-2

A portion of 0.5 g (0.712 mmol) of 4-1 was dissolved in 75mL of dry THF. To this solution

0.177 g (0.712 mmol) of nickel acetate was added and it was refluxed under nitrogen for 12

hours. The solution was cooled, filtered and the solvent removed. The solid was then washed

with pentane and filtered producing a red solid product in a 84% yield (0.45g). Crystals suitable

for X-ray diffraction were grown by a diffusion of ether into a saturated acetone solution. 1H

NMR: 6 8.22 (s, 2H); 7.84 (bs, 4H); 7.45 (m, 4H); 7.18 (s, 2H); 7.08 (t, 4H); 6.92 (m, 2H); 6.62

(s, 2H); 3.76 (m, 2H); 3.10 (m, 2H); 2.24 (m, 2H); 1.82 (m, 4H); 1.23 (s, 18H). 13C NMR 6

199.28; 158.60; 138.61; 128.82; 122.81; 122.19; 120.10; 118.75; 70.15; 34.20; 31.59;

28.96; 24.51. HRMS: Theoretical [M + Na] 781.2983; Measured 781.3002. Anal. Calc. for

C42H48N604Ni: C, 66.41; H, 6.37; N, 11.06. Found C, 66.13; H, 6.39; N, 11.00.

Synthesis of 4-3

A portion of 0.5 g (0.712 mmol) 4-1 was dissolved in 75 mL of dry diethyl ether. To this

solution 0.0824 g (1.56 mmol) sodium methoxide was added along with 0.195 g (0.783 mmol) of

palladium acetate. The solution was refluxed for 12 hours under nitrogen during which time a

green precipitate formed. The solution was cooled and the precipitate was filtered. The product

was redissolved in methylene chloride, filtered and then solvent was removed leaving a yellow

solid in a 48% yield (0.28 g). X-ray quality crystals were grown by a chloroform/pentane

diffusion. 1H NMR. 6 9.20 (s, 2H); 8.56 (s, 2H); 8.51 (d, J= 2.4 Hz, 2H); 8.12 (s, 2H); 7.46 s,

2H); 7.43 (s, 2H); 7.21 (s, 2H); 7.17 (m, 4H); 6.97 (t, J= 7.5 Hz, 2H); 3.55 (m, 2H); 2.75 (m,

4H); 1.82(m, 2H); 1.49(m, 2H); 1.28 (s, 18H). 13C NMR 6 157.48; 152.50; 151.34; 139.50;

136.31; 130.08; 128.56; 122.53; 121.87; 118.85; 118.48; 118.41; 72.23; 33.78; 31.30;

28.33; 24.05. HRMS: Theoretical [M + Na] 829.2676; Measured 829.2679.









Synthesis of 4-6

A portion often 0.157 g (1.08 mmol) was dissolved in 10 mL methanol. To this solution

was added 0.390 g (1.08 mmol) lutetium triflate. The solution was then heated to 500 c and

stirred open to air for 15 minutes. A 1.0 g portion (3.23 mmol) of 1-(5-tert-butyl-3-formyl-2-

hydroxyphenyl)-3-phenylurea was then dissolved in 25 mL of methanol, added to the solution

and stirred for 15 minutes. The solution was then filtered and allowed to slowly cool and

evaporate. After sitting for 12 hours large x-ray quality crystals had grown. These crystals were

filtered, crushed, and dried yielding a bright yellow powder in 45% yield (0.58 g). 1H NMR: 6

8.15 (s, 3H); 8.02 (m, 3H); 7.36 (s, 6H); 7.20 (m, 6H); 7.13 (m, 6H); 6.90 (m, 3H); 6.84 (m,

3H); 3.95 (m, 3H); 3.22 (d, 3H); 2.89 (m, 6H); 1.12 (s, 27H). 1C NMR 6 169.5; 156.3; 154.7;

139.0; 137.7; 129.9; 129.0; 124.2; 123.1; 120.6; 119.5; 60.1; 58.3; 34.1; 31.5. ). HRMS:

Theoretical [M + H] 1201.4882; Measured 1201.4898.

Synthesis of 4-7

A 1.0 g portion (3.23mmol) of 3-5 was dissolved in 50 mL of absolute ethanol. To this

solution was added 0.087 g (1.08 mmol) of tame. The reaction was refluxed open to the air for

12 hours. The solution was cooled to room temperature and filtered. To the filtrate was added

50 mL of water resulting in the precipitation of a bright orange solid. The solid was filtered and

dried to afford the product in 80% yield (0.86 g). 1H NMR in DMSO: 6 9.36 (s, 3H); 8.62 (s,

3H); 8.39 (s, 6H); 7.45 (d, 6H); 7.26 (t, 6H); 7.024 (d, 3H); 6.95 (t, 3H); 3.67 (s, 6H); 1.27 (s,

27H); 1.18 (s, 3H). HRMS: Theoretical [M + H] 1000.5389; Measured 1000.5444.

Synthesis of 4-8

A portion of 1.50 g (1.50 mmol) of 4-7 was dissolved in 15mL ethyl acetate. To this

solution a solution of 0.75g (3.00 mmol) of cobalt(II) acetate tetrahydrate in 50mL methanol was

added. A 3% solution of hydrogen peroxide (10 mL) was then added. The solution was then









brought to a boil for 5 min. The solution and suspended solid was then extracted with

chloroform (3 times 100 mL each). The extracts were washed several times with water, dried

with sodium sulfate and the solvent removed to afford the product in a 52% yield (0.818 g).

Crystals suitable for X-ray diffraction were grown by an acetone / pentane diffusion. 1H NMR: 6

7.91 (s, 3H); 7.74 (s, 3H); 7.56 (s, 3H); 7.27 (s, 3H); 7.23 (s, 3H); 7.05 (t, J= xx, 6H); 6.91 (s,

3H); 6.82 (t, 3H); 3.74 (d, 3H); 3.39 (d, 3H); 1.13 (s, 3H); 1.09 (s, 27H). 13C NMR 6 167.9;

155.5; 153.0; 139.4; 135.2; 131.1; 128.3; 122.6; 121.6; 121.0; 119.9; 118.2; 63.7; 40.6; 33.5;

31.0; 20.4. HRMS: Theoretical 1056.45; Measured 1056.45. Anal. Calc. for

C59H66N906Co-H20 :C, 65.96; H, 6.38; N, 11.74. Found C, 65.30; H, 6.48; N, 10.70.










Table 4-1. LogKs values of the two salen urea complexes with fluoride, chloride and bromide in
acetone.
Compound 4-2 Compound 4-3


F 6.10 6.09


C1 5.27 5.53


Br 4.29 4.67




Table 4-2. X-ray data from crystal structures of 4-2, 4-3, 4-4, 4-6, 4-8.

4-2 4-3 4-4 4-6 4-8


total reflections
unique
reflections
0max
crystal system
space group
a (A)
b (A)
c(A)
a (0)
V (K)

Vc (A')
z


19062
9861
28
triclinic
P-1
12.3151(6)
17.2793(8)
20.9637(9)
107.0500(10)
92.9510(10)
95.3330(10)
4231.9(3)
2


9871
6718
28
monoclinic
I2/a
17.6232(10)
17.2988(9)
28.011(2)
90.00
94.4040(10)
90.00
8514.3(9)
4


13587
6020
28
monoclinic
c2/c
43.56(3)
10.203(5)
26.868(16)
90.00
91.67(7)
90.00
11938(12)
6


16723
12542
28
monoclinic
P2(1)/c
15.0435(13)
25.384(2)
19.0081(17)
90.00
94.287(2)
90.00
7238.2(11)


4240
4015
28
triclinic
P
28.0319(11)
28.0319(11)
28.0319(11)
90.0
90.0
90.0
22027.1(15)
16













0

N N
I I
H H




Figure 4-1. Proposed structure and binding mode of an early urea based anion receptor.



Figure 4-1. Proposed structure and binding mode of an early urea based anion receptor.'


Figure 4-2. Structure of a urea subunit where the anion binding cavity is regulated by metal
coordination


N N

H H










H H
2 Eq. N
L I_ o


H2N NH2


Q
-N N-
/ OH HO / -
S NH HN>
NH HN
00- zz


Figure 4-3. Synthetic scheme for the formation of salen urea (compound 4-1)


Figure 4-4. Depiction of the solid-state structure of 4-2 (30% probability ellipsoids, carbons
drawn with arbitrary radii). The break in planarity of the urea group N5, 04, N6 is
caused by a steric clash between the two phenyl rings as well as an intramolecular
hydrogen bond between N3 and 04.






























Figure 4-5. Depiction of the solid-state structure of 4-3 (30% probability ellipsoids, carbons
drawn with arbitrary radii). The two urea groups are oriented to form an anion
binding cavity with four N-H groups available for hydrogen bonding










7000


6000

5000

4000

3000

2000

1000

0
330 350 370 390 410 430 450 470 490 510 530
Wavelength

Figure 4-6. UV-Vis titration of 4-2 with tetra-butylammonium fluoride in acetone. Titration was
complete after the addition of a single equivalent of fluoride.

















0.32


0.3


A 0.28


0.26


0.24


0.22
0 0.00005 0.0001 0.00015 0.0002 0.00025 0.0003
Concentration of Fluoride [M]
Figure 4-7. Binding constant data of 4-2 titrated with F- at 450nm Log Ks = 6.10. Each point
represents an experimental value and the best fit line is shown where a value of Ks is
calculated to minimize the error to the system.






























Figure 4-8. Depiction of the solid-state structure of 4-4 (30% probability ellipsoids, carbons
drawn with arbitrary radii, tetrabutylammonium cation and hydrogen removed for
clarity). The chloride is positioned above the plane of the molecule and the four urea
N-H's are distorted in order to be aligned with the anion.












0.25

< 0.2

0.15

._ 0.1

0.05

0
0 0.2 0.4 0.6 0.8 1
[L] / ([L] + [A])


Figure 4-9. Job plot of 4-2 for chloride. An apex in the plot at 0.5 indicated that there is a 1 : 1
ratio of anion to receptor in complex 4-4. [L] = concentration of receptor; [A] =
concentration of anion; 6 = NMR chemical shift.
































Figure 4-10. Depiction of the solid-state structure of 4-5 (30% probability ellipsoids, carbons
drawn with arbitrary radii, tetrabutylammonium cation and hydrogen removed for
clarity). The bromide is positioned above the plane of the molecule and the four urea
N-H's are distorted in order to be aligned with the anion.














5000 -


4500 -

4000

3500

3000

F 2500

2000

1500

1000

500


330 380 430 480 530
wavelength (nm)

Figure 4-11. UV-Vis titration of 4-2 with tetra-butylammonium chloride in acetone. Titration
was complete after the addition of a single equivalent of fluoride.














0.32

0.31


*
c- *


0.3

0.29

A 0.28

0.27

0.26


0.25

0.24


0 0.00005 0.0001 0.00015 0.0002 0.00025 0.0003 0.00035
Concentration of Chloride [M]


Figure 4-12. Binding constant data of 4-2 titrated with C1 at 450nm Log Ks =5.27. Each point
represents an experimental value and the best fit line is shown where a value of Ks is
calculated to minimize the error to the system.














H2N N--'- NH2

NH2


1.) Lu(lll) triflate

OH O
H H H O
2.) 3Eq. .
0e


Figure 4-13. Synthetic scheme for compound 4-6. The metal Lu (III) is first reacted with tren
and then the condensation reaction with the urea aldehyde to afford compound 4-6.
































Figure 4-14. Depiction of the solid-state structure of 4-6 (30% probability ellipsoids, carbons
drawn with arbitrary radii, hydrogens and water molecule removed for clarity).













H2N NH2


OH

N HO


Co(OAc)2


N


HO

HN
)=O 4-7


Figure 4-15. Synthesis of ligand 4-7 and C3 symmetric anion receptor 4-8.


H H
N ,N


3Eq.


OH O


HN

HN"0'


0
HN

H\




4-8


H202





































Figure 4-16. Depiction of the solid-state structure of 4-8 (30% probability ellipsoids, carbons
drawn with arbitrary radii, tetrabutylammonium cation and hydrogen removed for
clarity).









CHAPTER 5
DESIGNER LEWIS ACIDS; THE DEVELOPMENT OF EXTREMELY BULKY AND RIGID
DINUCLEAR CHIRAL CATALYSTS

Introduction

Metal salen compounds are used in a many catalytic systems as they are able to promote a

variety of organic transformations.79 80 Salens are formed by a condensation reaction between

salicylaldehyde and a diamine and are able to coordinate many different metal centers in a wide

range of oxidation states. Chiral salen catalysts are readily prepared with enantiomerically pure

diamines, are adept at a number of enantioselective reactions such as alkene epoxidation,81 and

the Diels Alder reaction,82 among numerous others.83

For the design of chiral catalysts, the geometry of the salen is essential to determine the

orientation of the substrate upon coordination to the binding site. Metals bound within the salen

are able to transfer their chirality to the products by binding the substrate through Lewis acidic

interactions. The approach of the substrate towards the catalyst and the metal center influences

the conformation of the product. In the design of asymmetric catalysts, it is important to control

the trajectory of the substrate.79 The conformation of the active site is influenced by many

factors including the size and oxidation state of the coordinating metal. The nature of the ligand

also plays an important role as the location and steric constraints of the substituents on the salen

can regulate the path of approach of the substrate.84

Jacobsen's Catalyst

Jacobsen's catalyst is perhaps the most influential and well known metal salen compound

(Figure 5-1) and it contains a Mn (III) metal center for the asymmetric epoxidation of olefins.81

Although chromium was used early to epoxidize olefins,85 Jacobson found manganese to be a

superior choice for this reaction as it proceeds through a Mn (V) oxo species.86 The generally

accepted catalytic cycle, depicted in Figure 5-2, involves two steps. In the first, the oxidant









transfers and atom to oxidize Mn (III) to Mn (V) oxo and this species reacts with the incoming

olefin to create the epoxide. The source of oxygen for the epoxidations is typically

iodosylbenzene, but other oxygen sources such as bleach or peroxide are also catalytically

competent.

Many different chiral diamines such as binapthylene87 and diphenyl88 are used as catalyst

backbones, but 1,2-diaminocyclohexane is among the most commonly used, due to the low cost

of the chiral form. A second generation Jacobsen type catalyst, with chiral diphenyl diamine and

binapthyl groups combines their chiral elements to influence the stereoselectivity of the reaction

(figure 5-3) .89 Not only do the bulky chiral groups influence the approach of the substrate to the

catalyst, but they cause a folding effect, altering the geometry at the metal center.

Lewis Acid Catalysts

Since chiral metal sales are able to transmit their geometry onto substrates they are often

employed as Lewis acid catalysts for many organic transformations. The Friedel-Crafts reaction,

the ene reaction, and Diels-Alder reaction employ ordinary Lewis acids such as AlC13, TiC14 and

BF3.90 Although these reactions proceed very efficiently; they are neither regio nor

stereoselective. Many biologically active molecules are chiral and the design of asymmetric

catalysts to facilitate carbon carbon bond formation is of particular importance to medicinal

chemistry and the pharmaceutical industry because many of their products require 99%

enantiomeric excess (e.e.).92 Modifying the ligands coordinated to the Lewis acidic metal can

lead to products with higher regio and enantioselectivity.

Zn Salens in Catalysis

Chiral Zn salen compounds can catalyze stereoselective organic transformations. For

example, a Lewis acidic Zn (II) can promote efficient addition of an ethyl group to aldehydes

with ee's ranging from 35-70 %.93 Unfortunately, the isolation of a pure metalated Zn (II) salen









is often problematic, and mixtures of metalated product and free ligand are obtained.79 To

overcome this challenge, metalation of the salen occurs in situ with Et2Zn, and the resulting

complex catalyzed at 10 mol. % to promote the addition of an ethyl group to benzaldehyde. The

proposed reaction mechanism involves the simultaneous coordination of the aldehyde and Et2Zn

to the Lewis acidic Zn salen. The manner in which the aldehyde orients itself when coordinating

to the metal center influences the stereochemistry of the product. The hydrogen atom of the

aldehyde aligns itself in order to minimize its interactions with the stereo centers.

Bifunctional Zn salen catalysts that contain both a Lewis acid and a Lewis base

component can promote the addition of an ethyl group to benzaldehyde with high efficiency and

stereoselectivity.94 The Lewis acidic Zn metal center coordinates and activates the aldehyde,

while the aminoalkoxy groups at the periphery of the salen are able to coordinate and activate

diethylzinc (Figure 5-5). Once activated, the substrates have an enhanced reactivity for the

addition of diethylzinc to aldehydes with respect to other Zn salen catalyst systems.93

While numerous methods promote asymmetric reactions with aldehydes, there are only a

handful of examples of reactions with ketones, which are generally considered to be unreactive

as substrates in asymmetric catalysis.95 Ketones are difficult substrates due to their low

reactivity as well as problems controlling their stereoselectivity.95 A Zn salen catalyst can

facilitate the stereoselective addition of terminal alkynes to a multitude of ketones with moderate

yields (30-90 %) and enantiomeric excess (30-81 %) (Figure 5-6).96 For the reaction to proceed,

a zinc alkynide forms in situ and associates with the salen phenolates. The ketone, which is

coordinated to the Lewis acidic Zn salen site, is then able to add the alkyne and a diagram of the

proposed transition state is depicted in figure 5-7.









The Promotion of the Diels-Alder Reaction by a Lewis Acid

The Diels-Alder reaction, which is one of the most widely used reactions in synthetic

organic chemistry can be facilitated by Lewis acid catalysts.97 While Diels-Alder reactions can

occur in the absence of a catalyst without stereoselectivity, at high temperature, the presence of a

chiral Lewis acid can initiate the reaction with higher selectivity. Among the chiral Lewis acid

catalysts able to promote the Diels-Alder reaction are organic iminium salts,98 and metal salen

complexes containing Co (III)99 or Cr (III).100

General Approaches of Synthetic Design

Although the work in the field of asymmetric catalysis is vast, there is always the need to

create systems that are more efficient and selective. Designer Lewis acidic catalysts can promote

a variety of organic transformations and particular interest has been paid to the development of

catalysts that can induce regio- and stereoselective products.101 The nature of the ligand as well

as the metal are crucial to the reactivity and selectivity of any catalyst, and modifications made

to the system can influence its properties. Herein, we report the design and synthesis of an

extremely bulky and rigid chiral Lewis acid catalyst.

Results and Discussion

For the design of Lewis Acidic catalysts, the salen macrocycle offers a convenient way to

create a system compatible with many different metal centers to promote a variety of organic

transformations. The presence of rigid and sterically bulky groups on the salen can enhance

stereoselectivity by blocking the catalytic site from substrate attack. Metal salen compounds are

ideal candidates for Lewis acid catalysts since they can facilitate many reactions efficiently and

selectively with metals such as Ti, Cr, Al, Co, and Zn among numerous others.79 The

environment of the metal affects stereoselectivity as the chirality at the metal center can translate

to the products.









Previous work with chiral metal salen compounds in the Scott lab has shown that four

phenols at the periphery of a salen can be orientated into a tetrahedral environment as in

compound 2-2.63 In the solid state structure of 2-2, R,R-1,2-diaminocyclohexane is chiral, but

this geometry is not translated to other parts of the ligand. The bulky phenols still have a lot of

rotational freedom and their position is not influenced by the chirality of the diamine. In the

solid state structure, two molecules crystallized in the asymmetric unit, each with a different

orientation of the phenols, indicating that the configuration of the system would not be useful as

a chiral catalyst (Figure 5-9).

Binap Ligand

In order to design a system where the chiral unit of the structure would translate its

geometry to the entire molecule, it must possess a larger torsion angle than R,R-1,2-

diaminocyclohexane. Binapthylene is a common moiety in many catalytic systems. It is chiral

and has a large angle between the two napthyl planes (Figure 5-10). The condensation of 2,2-

diamino-1,1-binapthylene with a portion of an aldehyde derivative of triphenoxymethane 5-1

affords compound 5-2 as depicted in Figure 5-11. Both chiral and racemic versions of ligand 5-2

were synthesized and there are noted differences in the properties of the two. The condensation

reaction of the racemic compound readily forms the product (5-2), but the chiral portion does not

cleanly convert to the desired product and column chromatography must be employed to isolate

the ligand (5-3). Once isolated both molecules have identical NMR and absorption spectra, but

have strikingly different solubilities. While 5-2 is soluble in only a handful of solvents such as

THF, methylene chloride and chloroform, compound 5-3 was soluble in all organic solvents

ranging from pentane to methanol.

The ability to manipulate a ligand's solubility is often important for the development of

catalysts as metalation reactions of sales often require the precipitation of the complex as a









means of isolating the product. Ligands which are extremely soluble will create difficulties in

the formation of the catalyst. In order to attempt to lower the solubility of the chiral system the

alkyl groups on the triphenoxymethane were changed from t-butyl to methyl groups which

would presumably diminish the compound's solubility in non-polar solvents. Both the racemic

(5-4) and chiral (5-5) versions of the di-methyl derivative were made and a depiction of the

synthetic scheme for the formation of 5-4 can be seen in figure 5-12.

The incorporation of the methyl groups did slightly decrease the solubility of the ligand

and a solid state structure of 5-4 was obtained (Figure 5-13). The structure shows that there is a

significant angle between the two napthyl planes of 98.60, which should force the geometry of

the entire molecule upon metalation. Unlike the structure of 2-1, there is a well defined twist in

the structure of the binap derivative and it is this twist that is critical to the design of our catalyst.

Racemic Zn Catalyst

All initial work in catalyst design involved the use of the racemic versions of the molecules

due to the lower cost of the starting diamine. The first area of concentration included the

metalation of the binap ligands with Zn (II). Zinc sales are useful as Lewis acid catalysts, and

have many useful properties including no redox activity or air sensitivity. Zn (II) also is

diamagnetic offering the ability to monitor the synthesis by 1H NMR spectroscopy. Metalation

of 5-2 and 5-4 with Zn(II) followed typical literature procedures by precipitating from an

acetonitrile solution upon metal complexation102 to form the methyl and the t-butyl derivatives 5-

6 and 5-7 respectively.

In solid state structure 5-6, the binapthylene influences the geometry of the entire molecule

(Figure 5-14). On each side of the structure, the phenols are orientated in the opposite direction

of the napthyl plane. There is a distinct twist to the molecule creating a channel in which

substrates could coordinate. There is enough space around the catalytic site for a substrate to









bind as the solid state structure has two THF solvent molecules coordinated to the Zn (II) metal

center, intimating the Lewis acid properties of the Zinc salen species. The majority ofZn salen

molecules are five coordinate,103 however, there are a few examples of six104 and four105

coordinate complexes. In the presence of a coordinating solvent such as THF, the metal center

of 5-6 assumes an octahedral geometry with the two THF molecules in the axial positions and

the four binding sites of the salen coordinating in the equatorial positions. The zinc oxygen

and zinc nitrogen distances of 5-6 are typical for Zn (II) binap salen compounds.106

The solid state structure of 5-6 was obtained in the coordinating solvent THF, but a

structure of 5-7 was obtained from a solution of the non-coordinating solvent methylene

chloride. There is a drastic difference between the two structures as the lack of a coordinating

solvent completely changes the geometry of the metal (figure 5-15). The metal center of 5-7 is

aligned in a tetrahedral geometry and the position of the four phenols is also quite different since

they are spaced much further apart. There is a greater twist to the structure of 5-7 than there is

for 5-6, but in both cases the geometry of the entire molecule is determined by the position of the

binaphthalene. The zinc oxygen and zinc nitrogen distances of 5-7 are typical for Zn (II)

binap salen compounds,106 while the geometry is a distorted tetrahedral with N(1) Zn(1) N(2)

angles of 96.6(4), and 0(1) -Zn() 0(4) andgles of 116.4(3).

While the position of the four phenols is influenced by the binaphthalene in the sold state,

these bulky groups contain a large degree of rotational freedom and would be dynamic in

solution. In order for an asymmetric catalyst to be effective, it must be able to force the

stereochemistry of the substrate. The extremely bulky groups, as seen in this system on the

periphery of the salen, could be an ideal means to do this, yet if the phenols are not rigidly

locked into position it will not be effective. The four phenols are aligned in a pseudo tetrahedral









array and the incorporation of another metal at this site would lock them into position creating an

extremely bulky and rigid multinuclear catalyst which would not be flexible in solution.

Ti (IV) will form complexes with four phenols arranging the phenolates into a tetrahedral

geometry.107 Since these complexes are do, the products can be readily observed by 1H NMR

spectroscopy. Initial attempts at metalation involving TiC14 and triethylamine as a base for the

deprotonation of the phenols were unsuccessful as a mixture of products was obtained. The

addition of one equivalent of titanium isopropoxide to a solution of 5-7 however, led to a clean

conversion to the desired catalyst 5-8 and a depiction of the solid state structure can be seen in

figure 5-16.

The incorporation of titanium not only rigidifies the system, but creates a channel for

substrate coordination to occur. The oxygen titanium bond lengths in the range of 1.799(2) A

to 1.828(2) A are typical for a Ti (IV) atom bound to four phenolates in a tetrahedral

environment204 and the titanium is very near this geometry with angles ranging from 104.3(10)

to 118.8(11)0. The phenol that includes 0(3) is aligned in a manner that blocks an entire side of

the metal center from substrate attack and in combination with the binaphthalene group forms an

ideal site for asymmetric catalysis to occur. Space filling models of 5-8 infer that the presence of

the t-butyl groups on the phenols is important to create the proper steric constraint to force the

stereoselectivity of the products (Figure 5-17). After this observance, no further effort was made

with ligand 5-4. Zinc behaves as a Lewis acid and coordinates a THF solvent molecule to one

side of the zinc in comparison to the structure of 5-6 which coordinates two THF molecules;

however, compound 5-8 only binds one solvent molecule because of the rigidity and steric

constraints placed on the system. The metal center is in a trigomal bipyramidal geometry as the

angle of 0(1) Znl -0(4) is 128.92(13) and the angle of 0(1) Zn(1) N(1) is 90.25(10).









Chiral Zn Catalyst

The synthesis of the target catalyst has proven the plausibility of the system, but in order to

be an effective asymmetric catalyst, a chiral molecule must be isolated, but the metalation of 5-3

with Zn (II) proved difficult. The synthesis of compound 5-6 involved the precipitation of the

product from the reaction mixture upon metalation. Due to the high solubility of 5-3, the chiral

complex never precipitated from the reaction mixture and all attempts to purify the mixture were

unsuccessful. A multitude of reaction conditions and purification techniques were screened with

none resulting in better than a 60 : 40 ratio of metalated compound to free ligand as determined

by 1H NMR spectroscopy. Difficulties in isolating chiral Zn salen compounds have been

previously noted with a mixture between the metalated and free ligand species being the

common product.79 Most systems employ an in situ metalation method with alkyl zincs such as

Et2Zn,93,94 but this is not a possibility for a multinuclear system as the Zn product must first be

isolated.

Co Catalysts

Since the isolation of a chiral Zn catalyst proved difficult, other metals were examined.

Both Co (II) and Co (III) are useful in asymmetric catalysis and have been able to promote

organic reactions with high efficiency and selectivity.109 Co salen compounds can

enantioselectively facilitate the Baeyer-Villiger oxidation,110 as well as the Diels-Alder reaction99

in good yields. The metalation of ligand 5-2 with Co (II) afforded the product 5-9. Although Co

(II) is paramagnetic, the compound synthesis could be monitored by 1H NMR spectroscopy.

(Figure 5-18).

In order to rigidify the system, titanium was once again coordinated to the four phenols to

lock in the geometry. The positions of the phenols have been influenced by the binaphthalene

and the solid state structure of this complex (5-10) is isostructural to that of 5-8. The ionic radii









of Zn (II) (0.880 A) and Co (II) (0.885 A) are nearly identical and the similarity is directly

translated to the structure (Figure 5-19). The metal ligand bond lengths are similar to other Co

(II) binaphthalene salen complexes,111 and both the bond lengths and angles from the titanium to

the phenolates are typical.108 Much like the Zn (II) system, the isolation of a chiral Co (II) was

problematic due to the high solubility of the complex, and it became apparent that in order to

isolate a chiral metal salen catalyst, the solubility of the ligand had to be altered.

Low Solubility Chiral Ligands

As a starting point for the formation of less soluble triphenoxymethane aldehydes, the

substituent in the R3 position of the molecule was changed (Figure 5-20). Both 2,6-diformyl-4-

bromophenol and 2,6-diformyl-4-nitrophenol are known,112 and the incorporation of either the

bromo or nitro group to the system decreased the solubility of the molecule. The synthetic

scheme for the triphenoxymethane aldehyde compounds can be seen in figure 5-21 and both the

bromo (5-11) and the nitro (5-12) derivatives were readily isolated.

The condensation reaction of R,R-(+)-2,2-diamino-1,1-binapthylene and the aldehydes 5-

11 and 5-12 afforded the chiral ligands 5-13 and 5-14 (Figure 5-22). The solubility of the

ligands in polar and non-polar solvents is considerably lower than that of complexes 5-3 and 5-5,

and the isolation of the chiral Lewis acid catalysts is attainable. The addition of a large excess of

Co (II) to 5-13 and 5-14 in methanol led to the precipitation of the pure compounds 5-15 and 5-

16 respectively. While the metalation of 5-13 with Zn (II) was unsuccessful the addition of a

large excess of the metal to 5-14 fostered the clean conversion to 5-17.

In the solid state structure of 5-16, Co (II) is in an octahedral geometry with four bonds

from the salen ligand and two coordinating methanol molecules (Figure 5-24). The coordination

of methanol to the metal center has an effect on the solubility of the compound, as the reaction

does not cleanly convert to product in other solvents. While other compounds in this chapter









have crystallized as a single enantiomer, 5-16 was the first structure of a metalated enantiopure

compound with R-(+)-2,2-diamino-1,1-binapthalene as a backbone. The four phenols of

compound 5-16 are rigidified by the addition of titanium created an extremely bulky and rigid

chiral, Lewis acid catalyst (5-18).

Initial Catalysis Studies

Throughout the process of catalyst development, the ability of the metal complexes to

facilitate organic transformations has been monitored as a means to judge the feasibility of the

system. The standard reaction used to determine catalyst activity was the addition of an ethyl

group to benzaldehyde. In order for this reaction to occur, a Lewis acid catalyst must be present

and there are many examples of Zn salen systems promoting this reaction in high yields (Figure

5-25).93

The catalytic ability of the racemic Zn (II) (5-8) and Co (II) (5-10) complexes were tested

and both were able to transform the reaction in quantitative yields (96-98 %). There was no

indication of any remaining benzaldehyde in the 1H NMR spectrum of the crude product. The

reaction mixture contains both the alcohol product and the catalyst, but upon workup the catalyst

can be recovered and reused in other reactions. The reactivity of 5-7 and 5-9 was also examined

and not surprisingly they both were also able to promote this reaction. The absence of the

titanium should have little impact on the reactivity at the Lewis acid site, but rather is important

to lock in the chiral geometry of the system to increase enantioselectivity.

Conclusions

The ability to devise new asymmetric catalysts is of great importance to the field of

synthetic organic chemistry. For this purpose, a class of multinuclear salen based, chiral Lewis

acid catalysts have been developed. Both Zn (II) and Co (II) derivatives have been made and

initial studies have indicated that they are able to promote the ethyl addition to benzaldehyde.









The reactivity of the system with countless other reactions has still yet to be explored. The

chirality of the system is determined by the binap group as its large torsion angle is able to set

the geometry of the entire compound. The addition of titanium to coordinate to the four phenols

is able to rigidify the molecule and "lock in" the chirality.

Experimental Methods

General Considerations

1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at

299.95 and 75.47 MHz for the proton and carbon channels. UV-Vis spectra were recorded on a

Varian Cary 50 spectrometer. Elemental analyses were performed at either the in-house facility

of the Department of Chemistry at the University of Florida or by Complete Analysis

Laboratories Inc., Parsippany, NJ. All solvents were ACS or HPLC grade and used as

purchased. For the metalation reactions, the solvents were dried with a Meyer Solvent

Purification system.

Synthesis of 5-2

A portion of 1.00 g (3.52mmol) of racemic 1,1'-Binapthyl-2-2'-diamine was dissolved in

250 mL absolute ethanol. To this solution a portion of 3.34 g (7.04 mmol) of 5-1 was added.

The reaction was refluxed open to the air for 12 hours. The solution was cooled to room

temperature and water was added to the solution resulting in the precipitation of an orange solid.

The solid was filtered and dried to afford the product in 90% yield (3.81 g). Crystals suitable for

X-ray diffraction were grown by a THF / pentane diffusion. H NMR: 6 13.20 (s, 2H); 8.49 (s,

2H); 8.12 (d, 2H, 9.3 Hz); 7.00 (d, 2H, 8.7 Hz); 7.46 (m, 2H); 7.29 (m, 6H); 7.05 (s, 2H); 6.98 (s,

2H); 6.93 (s, 2H); 6.78 (s, 2H); 6.65 (s, 2H); 6.56 (s, 2H); 5.63 (s, 2H); 5.42 (s, 2H); 5.07 (s,

2H); 2.19 (s, 6H); 2.14 (s, 6H); 2.12 (s, 6H); 1.45 (s, 18H); 1.32 (s, 18H). 13C NMR 6 161.9;

155.8; 151.4; 151.2; 143.8; 137.7; 137.4; 135.1; 133.2; 132.9; 131.6; 130.7; 129.3; 128.9; 128.8;









128.7; 128.4; 128.1; 127.6; 127.5; 127.4; 127.3; 127.0; 126.9; 126.8; 126.3; 199.1; 117.0; 37.1;

35.1; 34.9; 30.1; 30.0; 21.3; 20.7. Anal. Calc. for C82H8806N2: C, 82.37; H, 7.26; N, 2.34. Found

C,82.10; H, 2.61; N, 2.21.



Synthesis of 5-3

A portion of 1.00 g (3.52mmol) ofR-(+)-1,1'-Binapthyl-2-2'-diamine was dissolved in 250

mL absolute ethanol. To this solution a portions of 3.34 g (7.04 mmol) of 5-1 was added. The

reaction was refluxed open to the air for 12 hours. The solution was cooled and the solvent

removed under vacuum. The solid was dissolved in the minimum amount of methylene chloride

and filtered through a plug of alumina. The solvent was then removed to afford the product in

75% yield (3.14 g). 1H NMR: 6 13.20 (s, 2H); 8.49 (s, 2H); 8.12 (d, 2H, 9.3 Hz); 7.00 (d, 2H, 8.7

Hz); 7.46 (m, 2H); 7.29 (m, 6H); 7.05 (s, 2H); 6.98 (s, 2H); 6.93 (s, 2H); 6.78 (s, 2H); 6.65 (s,

2H); 6.56 (s, 2H); 5.63 (s, 2H); 5.42 (s, 2H); 5.07 (s, 2H); 2.19 (s, 6H); 2.14 (s, 6H); 2.12 (s,

6H); 1.45 (s, 18H); 1.32 (s, 18H). 13C NMR 6 161.9; 155.8; 151.4; 151.2; 143.8; 137.7; 137.4;

135.1; 133.2; 132.9; 131.6; 130.7; 129.3; 128.9; 128.8; 128.7; 128.4; 128.1; 127.6; 127.5; 127.4;

127.3; 127.0; 126.9; 126.8; 126.3; 199.1; 117.0; 37.1; 35.1; 34.9; 30.1; 30.0; 21.3; 20.7. HRMS:

calcd for C82H8806N2 1197.6715; found 1197.6715 [MH+].

Synthesis of 5-4

A portion of 1.00 g (3.52mmol) of racemic 1,1'-Binapthyl-2-2'-diamine was dissolved in

250 mL absolute ethanol. To this solution a portion of 2.75 g (7.04 mmol) of 3-(bis(2-hydroxy-

3,5-dimethylphenyl)methyl)-2-hydroxy-5-methylbenzaldehyde was added. The reaction was

refluxed open to the air for 12 hours. The solution was cooled to room temperature and water

was added to the solution resulting in the precipitation of a pink solid. The solid was filtered and

dried to afford the product in 87% yield (3.14 g). H NMR: 6 13.22 (s, 2H); 8.44 (s, 2H); 8.07 (d,









2H, 9 Hz); 7.98 (d, 2H, 8 Hz); 7.51 (d, 2H, 9 Hz); 7.46 (t, 2H, 8 Hz); 7.25 (t, 2H, 9 Hz); 6.93 (s,

2H); 6.88 (s, 2H); 6.82 (s, 2H); 6.72 (s, 2H); 6.65 (s, 2H); 6.59 (s, 2H); 5.71 (s, 2H); 5.38 (s,

2H); 5.10 (s, 2H); 2.26 (s, 6H); 2.18 (s, 6H); 2.15 (s, 6H); 2.14 (s, 6H); 2.11 (s, 6H). 13C NMR

162.1; 156.1; 150.4; 143.6; 134.5; 133.5; 133.3; 132.8; 131.5; 130.6; 130.5; 129.3; 129.2; 129.2;

129.1; 128.9; 128.7; 128.2; 127.4; 127.2; 126.9; 126.1; 125.6; 125.4; 119.1; 117.0. HRMS:

calcd for C70H6406N2 1029.4837; found 1029.4794 [MHi].

Synthesis of 5-5

A portion of 1.00 g (3.52mmol) of R-(+)- 1,1'-Binapthyl-2-2'-diamine was dissolved in

250 mL absolute ethanol. To this solution a portions of 2.75 g (7.04 mmol) of 3-(bis(2-hydroxy-

3,5-dimethylphenyl)methyl)-2-hydroxy-5-methylbenzaldehyde was added. The reaction was

refluxed open to the air for 12 hours. The reaction was cooled and the solvent was removed

under vacuum. The solid was dissolved in the minimum amount of methylene chloride and

filtered through a plug of neutral alumina with a 90:10 methylene chloride:methanol mixture.

The solvent was removed to afford an orange solid in 71% yield (2.57 g). 1H NMR: 6 13.22 (s,

2H); 8.44 (s, 2H); 8.07 (d, 2H, 9 Hz); 7.98 (d, 2H, 8 Hz); 7.51 (d, 2H, 9 Hz); 7.46 (t, 2H, 8 Hz);

7.25 (t, 2H, 9 Hz); 6.93 (s, 2H); 6.88 (s, 2H); 6.82 (s, 2H); 6.72 (s, 2H); 6.65 (s, 2H); 6.59 (s,

2H); 5.71 (s, 2H); 5.38 (s, 2H); 5.10 (s, 2H); 2.26 (s, 6H); 2.18 (s, 6H); 2.15 (s, 6H); 2.14 (s,

6H); 2.11 (s, 6H). 13C NMR 6 162.1; 156.1; 150.4; 143.6; 134.5; 133.5; 133.3; 132.8; 131.5;

130.6; 130.5; 129.3; 129.2; 129.2; 129.1; 128.9; 128.7; 128.2; 127.4; 127.2; 126.9; 126.1; 125.6;

125.4; 119.1; 117.0. HRMS: calcd for C70H6406N2 1029.4837; found 1029.4794 [MH+].

Synthesis of 5-6

A portion of 0.25 g (0.24 mmol) of racemic 5-4 was dissolved in a minimum amount of

methylene chloride. To this solution was added 200 mL of acetonitrile as well as a portion of

0.059 g (0.27 mmol) of Zinc acetate 2 H20. The solution was stirred and heated at 750 C for









four hours. A yellow precipitate forms and the solid was filtered and dried to afford the product

in 82% yield (0.21 g). Crystals suitable for X-ray diffraction were grown by a THF / pentane

diffusion. 1H NMR: 6 8.33 (s, 2H); 8.06 (d, 2H, 9 Hz); 7.88 (d, 2H, 9 Hz); 7.45 (s, 2H); 7.42 (m,

2H); 7.21 (m, 4H); 6.86 (d, 2H, 12 Hz); 6.81 (s, 2H); 6.78 (s, 6H); 6.71 (s, 2H); 6.64 (bs, 2H);

6.38 (s, 2H); 6.33 (bs, 2H); 2.14 (s, 6H); 2.11 (s, 6H); 2.03 (s, 6H). Unable to obtain 13C NMR

due to low solubility. HRMS: calcd for C70H6206N2Zn 1091.3972; found 1091.3870 [MH+].

Synthesis of 5-7

A portion of 2.00 g (1.67 mmol) of racemic 5-2 was dissolved in a minimum amount of

methylene chloride. To this solution was added 200 mL of acetonitrile as well as a portion of

0.46 g (2.10 mmol) of Zinc acetate 2 H20. The solution was stirred and heated at 750 C for

four hours at which time a yellow precipitate formed. The solid was filtered and dried to afford

the product in 89% yield (1.87 g). 1H NMR: 6 8.32 (s, 2H); 8.00 (d, 2H, 8.7 Hz); 7.89 (d, 2H,

8.7 Hz); 7.43 (m, 4H); 7.21 (m, 4H); 6.96 (m, 6H); 6.89 (d, 2H, 8.7 Hz); 6.82 (d, 4H, 7.8 Hz);

6.77 (s, 2H); 6.29 (s, 2H); 6.07 (s, 2H); 2.18 (s, 6H); 2.12 (s, 12H); 1.38 (s, 18H); 1.24 (s, 18H).

13C NMR6 171.3; 164.4; 152.1; 152.0; 144.7; 139.2; 137.5; 137.4; 135.0; 134.1; 133.8; 132.4;

131.4; 128.7; 128.5; 128.3; 128.1; 127.4; 127.3; 127.0; 126.6; 126.5; 126.4; 126.0; 125.7; 125.3;

121.4; 118.1; 35.1; 34.9; 30.1; 29.9; 21.3; 21.2; 20.4. HRMS: calcd for C82H8606N2Zn

1259.5730; found 1259.5850 [MHi].

Synthesis of 5-8

A portion of 0.50g (0.39 mmol) of 5-7 was partially dissolved in 50 mL of dry methylene

chloride under nitrogen. To this solution was added a portion of 0.12 g (0.44 mmol) titanium

isopropoxide. The solid instantly dissolved into the solution which turned dark red. The

solution was allowed to stir for 12 hours in the dry box at which time the solvent was removed in

vacuum yielding pure product in 95% yield (0.49 g). Crystals suitable for X-ray diffraction









were grown by a pentane diffusion into an acetonitrile / THF solvent mixture. 1H NMR: 6 8.21

(s, 2H); 7.95 (d, 2H, 9 Hz); 7.85 (d, 2H, 9 Hz); 7.58 (s, 2H); 7.39 (t, 2H); 7.14 (t, 2H); 7.02 (s,

2H); 7.00 (s, 2H); 6.79 (s, 2H); 6.75 (d, 2H); 6.70 (s, 4H); 5.84 (s, 2H); 2.39 (s, 6); 2.22 (s, 6H);

2.15 (s, 6H); 1.40 (s, 18H); 0.99 (s, 18H). 13C NMR 6 170.2; 170.0; 160.4; 160.3; 145.4; 140.9;

137.1; 135.8; 134.8; 134.7; 134.1; 132.2; 130.9; 130.7; 130.6; 129.2; 128.3; 127.0; 126.7; 126.5;

126.3; 125.8; 125.7; 123.8; 123.7; 121.9; 117.4; 65.8; 44.1; 35.5; 34.5; 30.4; 30.0; 29.7; 25.4;

22.5; 21.2; 21.1; 2016; 15.3; 13.9.

Synthesis of 5-9

A portion of 1.00 g (0.84 mmol) of racemic 5-2 was dissolved in 50 mL of methylene

chloride. A portion of 0.266 g (1.07 mmol) of cobalt(II) acetate 4 H20 was dissolved in the

minimum amount of methanol under nitrogen. The cobalt solution was added to the ligand

solution under nitrogen and stirred for two hours. A red /orange precipitate formed and was

quickly filtered and dried to afford the product in 87% yield (0.92 g). 1H NMR: paramagnetic

signals 6 59.75; 53.98; 40.96; 15.69; 12.88; 9.13; 8.32; 7.77; 5.79; 3.87; 2.27; -1.67; -4.83; -10.3;

-50.87. HRMS: calcd for C70H6206N2Co 1254.5891; found 1254.5818 [M-H]+.

Synthesis of racemic 5-10

A portion of 1.00 g (0.79 mmol) of racemic 5-9 was partially dissolved in 50 mL of dry

methylene chloride under nitrogen. To this solution was added a portion of 0.24 g (0.87 mmol)

titanium isopropoxide. The solid instantly dissolved into the solution which turned dark red.

The solution was allowed to stir for 12 hours in the dry box at which time the solvent was

removed in vacuum yielding pure product in 92% yield (0.95 g). Crystals suitable for X-ray

diffraction were grown by a pentane diffusion into an acetonitrile / THF solvent mixture. 1H

NMR: 6 64.56; 61.92; 46.92; 15.02; 11.79; 9.25; 7.55; 7.23; 7.17; 6.09; 5.28; 4.77; 4.05; 3.70;

3.48; 2.34; 1.84; 1.02; 0.87; -4.43; -4.80; -7.25; -7.84; -12.12; -48.1









Synthesis of 5-11

A portion of 1 g (4.37 mmol) of 2,5-diformyl-4-bromo-phenol was added to a portion of

1.79 g (10.9 mmol) of 2-t-butyl-4-methyl-phenol. To this was added the minimum amount of

trifluoroacetic acid needed to fully dissolve the solids. The reaction was allowed to stir at room

temperature for 12 hours at which point a white solid precipitated. Cold methanol was added to

the reaction mixture and the product was filtered. The filtrate was taken and the solvent removed

under vacuum to yield a solid which was the washed with cold methanol affording more pure

product. The product was a white solid and was afforded in 76 % yield (1.8 g). 1H NMR: 6

11.40 (s, 1H); 9.89 (s, 1H); 7.68 (s, 1H); 7.33 (s, 1H); 7.07 (s, 2H); 6.54 (s, 2H); 5.99 (s, 1H);

2.20 (s, 6H); 1.38 (s, 18H). 13C NMR 6 195.7; 158.1; 151.0; 140.2; 137.8; 134.9; 133.91; 129.9;

127.8; 127.3; 126.5; 121.7; 112.0; 39.3; 34.7; 30.0; 21.3 HRMS: calcd for C30H3504Br

538.1719.; found 538.1680.

Synthesis of 5-12

A portion of 2.00 g (10.24 mmol) of 2,5-diformyl-4-nitro-phenol was added to a portion of

4.20 g (25.6 mmol) of 2-t-butyl-4-methyl-phenol. To this was added the minimum amount of

trifluoroacetic acid needed to fully dissolve the solids. The reaction was allowed to stir at room

temperature for 12 hours at which point a white solid precipitated. Cold methanol was added to

the reaction mixture and the product was filtered. The filtrate was taken and the solvent removed

under vacuum to yield a solid which was the washed with cold methanol affording more pure

product. The product was a white solid and was afforded in 44 % yield (2.3 g). 1H NMR: 6

12.05 (s, 1H); 10.0 (s, 1H); 8.52 (d, 1H, 2.7 Hz); 8.22 (d, 1H, 2.7 Hz); 7.10 (s, 2H); 6.52 (s, 2H);

6.08 (s, 1H); 2.22 (s, 6H); 1.39 (s, 18H). 13C NMR 6 195.8; 163.9; 150.0; 140.9; 137.7; 133.6;

131.9; 130.1;128.5; 128.0; 127.4; 127.3; 126.4; 119.3; 116.6; 39.5; 34.7; 30.1; 29.8; 21.3

HRMS: calcd for C30H3506N + Na 528.2357.; found 528.2359 [M+Na]+









Synthesis of 5-13

A portion of 0.50 g (1.75 mmol) ofR-(+)-l,1'-Binapthyl-2-2'-diamine was dissolved in

150 mL absolute ethanol. To this solution a portion of 1.84 g 5-11 was added. The reaction was

refluxed open to the air for 12 hours. A pale orange precipitate had formed and was filtered

which was pure product. The solvent of the filtrate was removed under vacuum and the

remaining solid was dissolved in the minimum amount of methylene chloride and filtered

through a plug of alumina. The solvent was then removed and the combination led to a

combined 68% yield (1.59 g). 1H NMR: 6 13.42 (s, 2H); 8.51 (s, 2H); 8.11 (d, 2H, 9 Hz); 7.99

(d, 2H, 9 Hz); 7.60 (d, 2H, 9 Hz); 7.49 (t, 2H, 9 Hz); 7.34 (m, 2H); 7.18 (d, 4H, 9 Hz); 7.06 (s,

2H); 7.00 (s, 2H); 6.57 (s, 2H); 6.51 (s, 2H); 5.60 (s, 2H); 5.19 (s, 2H); 4.96 (s, 2H); 2.18 (s,

6H); 2.15 (s, 6H); 1.43 (s, 18H); 1.34 (s, 18H). 13C NMR 6 160.1; 157.3; 151.1; 151.0; 142.6;

137.7; 137.6; 136.7; 133.2; 133.1; 133.0; 131.5; 130.9; 129.8; 129.4; 129.3; 128.8; 127.5; 127.3;

127.1; 127.0; 126.9; 126.8; 126.7; 120.6; 116.4; 111.0; 37.3; 35.0; 34.9; 30.1; 30.0; 21.3; 21.2.

HRMS: calcd for CsoH8206N2Br2 1325.4618.; found 1325.4368 [MH+].

Synthesis of 5-14

A portion of 0.475 g (1.67mmol) ofR-(+)-1,1'-Binapthyl-2-2'-diamine was dissolved in 150

mL absolute ethanol. To this solution a portion of 1.63 g (3.33 mmol) of 5-12 was added. The

reaction was refluxed open to the air for 12 hours. The reaction was cooled and the solvent was

removed under vacuum to afford the product in 97% yield (2.04 g). 1H NMR: 14.65 (bs, 2H);

8.71 (s, 2H); 8.14 (m, 4H); 7.99 (m, 2H); 7.93 (d, 2.4 Hz, 2H); 7.84 (m, 2H); 7.68 (d, 9 Hz,

2H); 7.52 (m, 2H); 7.34 (m, 2H); 7.23 (m, 4H); 7.07 (s, 2H); 7.03 (s, 2H); 6.85 (m, 2H); 6.57

(s, 2H); 6.51 (s, 2H); 6.48 (s, 2H); 5.65 (s, 2H); 2.14 (s, 6H); 7.13 (s, 6H); 1.42 (s, 18H);

1.39 (s, 18H). 6 13C NMR 6 166.1; 159.4; 151.0; 150.9; 104.3; 139.5; 137.7; 133.4; 137.7;

133.4; 133.1; 132.3; 131.4; 129.7; 129.5; 129.4; 129.2; 128.9; 128.7; 128.0; 127.5; 127.3; 127.1;









127.0; 126.9; 126.8; 126.7; 126.6; 117.2; 116.6; 115.8; 37.9; 34.9; 34.8; 30.1; 30.0; 29,8; 21.3.

HRMS: calcd for CsoH82010N4 1259.6104 .; found 1259.6134 [M+H]+

Synthesis of 5-15

A portion of 0.50 g (0.40 mmol) of 5-14 was dissolved in 150 mL methanol. To this

solution a large excess of Cobalt acetate 1.00 g (4.00 mmol) was added. The reaction was

brought to a boil under nitrogen at which point the heat was removed and the reaction was stirred

for 4 hours. A brown precipitate had formed and was quickly filtered to afford the pure product

in 81% yield (0.84 g). 1H NMR: 6 59.51; 53.39; 18.70; 16.81; 12.95; 9.13; 8.18; 7.06; 5.83; 4.61;

3.90; 2.92; 2.15; 1.90; 1.52; 1.32; 0.86; -1.18; -3.39; -5.49; -7.99; -9.61; -14.80; -53.96. HRMS:

calcd for CsoH0oO0oN4Co 1315.5201; found 1315.5205.

Synthesis of 5-16

A portion of 1.00 g (0.75 mmol) of 5-13 was dissolved in 150 mL methanol. To this

solution a large excess of Cobalt acetate 1.88 g (7.70 mmol) was added. The reaction was

brought to a boil under nitrogen at which point the heat was removed and the reaction was stirred

for 4 hours. A brown precipitate had formed and was quickly filtered to afford the pure product

in 81% yield (0.84 g). 1H NMR: 6 60.20; 55.46; 16.04; 12.86; 10.50; 9.06; 8.37; 7.55; 6.97; 5.79;

5.43; 4.91; 3.50; 2.07; 1.79; 1.35; 1.26; -1.01; -1.49; -2.95; -3.15; -4.51; -10.39; -51.76. HRMS:

calcd for CsoHsoO6N2Br2Co 1382.3793; found 1382.3448 [MH+].

Synthesis of 5-17

A portion of 0.50 g (0.40 mmol) of 5-14 was dissolved in 150 mL methanol. To this

solution a large excess of Zinc acetate 1.00 g (4.00 mmol) was added. The reaction was brought

to a boil under nitrogen at which point the heat was removed and the reaction was stirred for 4

hours. A yellow precipitate had formed and was quickly filtered to afford the pure product in

54% yield (0.285 g). 1H NMR: 6 8.44 (s, 2H); 8.07 (m, 6H); 7.97 (d, 2H, 9 Hz); 7.48 (t, 2H, 7.5









Hz); 7.32 (d, 2H, 9 Hz); 7.00 (s, 4H); 6.90 (d, 2H, 9 Hz); 6.76 (s, 2H); 6.54 (s, 2H); 6.21 (s, 2H);

5.94 (s, 2H); 5.42 (s, 2H); 2.19 (s, 6H); 2.13 (s, 6H); 1.34 (s, 18H); 1.28 (s, 18H). 13C NMR 6

172.4; 170.3; 151.0; 150.9; 144.0; 138.1; 136.9; 136.7; 133.6; 132.5; 132.3; 131.5; 130.0; 129.7;

129.5; 128.7; 128.4; 127.9; 127.6; 127.4; 127.2; 126.8; 126.6; 126.5; 125.5; 121.2; 117.2; 37.8;

35.0; 34.8; 30.1; 21.3; 21.1. HRMS: calcd for CsoHsoOioN4Zn 1320.5106; found 1320.5119.


























Figure 5-1. Structure of Jacobsen's catalyst used for the asymmetric epoxidation of olefins


NaCI








NaOCI


R









R,
O7
0


Figure 5-2. Proposed mechanism for the epoxidation of olefins with Jacobsen's catalyst.





















Figure 5-3. Structure of catalyst with chiral binapthyl groups that influence the geometry of the
substrate.





-N, ,N-
Zn
o/ 0 /
0 OH


Et2Zn


Figure 5-4. Reaction scheme for the ethyl addition to benzaldehyde. The reaction is promoted
by the chiral Lewis acidic Zn-salen catalyst.








SLewis Acid

0 N
Lewis Base

Figure 5-5. Structure of a bifunctional catalyst containing both a Lewis acid and Lewis base
component.




















O


Me2Zn
R H


OH R
OkR


Figure 5-6. Schematic diagram of the enantioselective alkynation of ketones.


Figure 5-7. Proposed transition state for the alkynation of ketones with a zinc salen catalyst


Catalyst


CHO


Figure 5-8. Diels-Alder reaction between cyclopentadiene and cinnamaldehyde promoted by a
Lewis acid catalyst.


































Figure 5-9. Solid state structure of compound 2-2. The chirality of the cyclohexane ring does
not affect the position of the four phenols.






NH2 /NH2
NH2 NH2



Figure 5-10. Depiction of 2,2-diamino-1,1-binapthalyene showing the large torsion angle
between the two napthyl planes.










/~\ /~\

\/ '\N/


\ 0 OHI OH
/ +2 Eq. H -

NH2 H2N HO

5-1



Figure 5-11. Synthetic scheme for the synthesis of 5-2.












) OH OH
S/ \/ +2 Eq. H OH

NH2 H2N HO


Figure 5-12. Synthetic scheme for the formation of 5-4. The t-butyl groups of the
triphenoxymethane have been replaced by methyl groups.
































Figure 5-13. Solid state structure of compound 5-4 (30% probability ellipsoids for nitrogen
and,oxygen; carbons drawn with arbitrary radii)






























Figure 5-14. Solid state structure of 5-6 with two THF solvent molecules coordinated to the
zinc. The geometry of the napthyl rings sets the position of the four phenols. (30%
probability ellipsoids for zinc, nitrogen and oxygen; carbon atoms drawn with
arbitrary radii, non coordinated solvents and hydrogen atoms were removed for
clarity)



































Figure 5-15. Solid state structure of compound 5-7. Without the presence of a coordinating
solvent, the metal center takes a tetrahedral geometry. (30% probability ellipsoids for
zinc, nitrogen and oxygen; carbons drawn with arbitrary radii, solvents and hydrogen
atoms were removed for clarity)




































Figure 5-16. Solid state structure of the dinuclear catalyst 5-8. A Zn (II) metal is coordinated in
the salen binding site and Ti (IV) is coordinated to the four phenols creating a rigid
structure. (30% probability ellipsoids for zinc, titanium, nitrogen and, oxygen;
carbon atoms drawn with arbitrary radii; THF and acetonitrile solvent molecules and
hydrogen atoms were removed for clarity)





































Figure 5-17. Space filling models of the solid state structure of 5-8. The catalytic site of Zn (II)
is represented in purple (right), and the chiral cavity formed for possible substrate
binding can clearly be seen. The titanium is deeply buried in the phenolic pocket
(left)


- -- ----- ----- ------ -----
__________,________
__1.__________-______-__A.___________


-20


-40 ppm


Figure 5-18. H NMR spectrum of the paramagnetic compound 5-9 in CDCl3.


-~C i .' ho -'-- M I. I .






































Figure 5-19. Solid state structure of the dinuclear compound 5-10




R2 \ R,

O OH OH



HO
R3 R1



Figure 5-20. Schematic of triphenoxymethane aldehyde showing its possible positions for ligand
modification.















O OH 0




R3
R3 = Br, NO2


TFA


Compound 5-11 R3 = Br
Compound 5-12 R3 = NO2


Figure 5-21. Synthetic scheme for compounds 5-11 and 5-12


NH2 /2N
NH2 H2N


R = Br Compound 5-11
R = NO2 Compound 5-12


R = Br Compound 5-13
R = NO2 Compound 5-14


Figure 5-22. Synthetic scheme for the synthesis of 5-13 and 5-14


+2 Eq.


























M = Co (ll) Compound 5-15 Compound 5-16
M = Zn (ll) Compound 5-17


Figure 5-23. Schematic diagram of the structures of 5-15, 5-16, and 5-17.


Figure 5-24. Crystal structure of 5-16; Co (II) is arranged in an octahedral geometry.












O


OH


Catalyst

Et2Zn


Figure 5-25. Catalytic reaction of the ethyl addition to benzaldehyde used as a standard to
monitor the catalytic ability of the compounds









LIST OF REFERENCES


1) Bianchi, E.; Bowman-James, K.; Garcia-Espana, E., Eds. Supramolecular Chemstry of
Anions: Wiley-VCH: New York, 1997.

2) Sessler, J.; Gale, P.; Cho, W. Anion Receptor Chemistry : RSC Publishing : Cambridge,
2006.

3) Alberts, B.; Bray, D.; Lewis, M.; Raff, M.; Roberts, K.; Watson, J. Molecular Biology
of the Cell, 3rd edn, Garland Science, New York, 1994.

4) Anderson, M.; Gregory, R.; Thompson, P.; Souza, D.; Paul, S.; Mulligan, A.; Smith,
A.; Welsh. Science. 1991, 253, 202.

5) Simon, D.; Bindra, R.; Mansfield, T.; Nelson-Williams, C.; Mendonca, E.; Stone, R.;
Schurmann, S.; Nayir, A.; Alpay, H.; Bakkaloglu, A.; Rodriguez-Soriano, J.; Morales,
J.; Sanjad, S.; Taylor, C.; Pilz, D.; Brem, A.; Trachtman, H.; Griswold, W.; Richard,
G.; Lifton, J. Nat. Genet.. 1997, 17, 171.

6) Devuyst, O.; Christie, P.; Courtoy, P.; Beauwens, R.; Thakker, R. Hum. Mol. Genet
1999, 8, 247.

7) Scott, D.; Wang, R.; Kreman, T.; Sheffield, V.; Karniski, L. Nat. Gen. 1999, 21, 440.

8) Yoshida, A.; Taniguchi, S.; Hisotome, I.; Royaux, I.; Green, E. ; Kohn, L. ; Suzuki, K.
J. Clin. Endo. Metab. 2002, 87, 3356.

9) For Examples: (a) Schmitdchen, F.; Berger, M. Chem. Rev 1997. 97, 1609. (b)
Antonisse, M.; Reinhoudt, D. Chem. Comm. 1998. 443. (c) Martinez-Manez, R.;
Sancenon, F. Chem. Rev. 2003. 103, 4419.

10) For example: Woods, C.; Camiolo, S.; Light, M. E.; Coles, S. J.; Hursthouse, M. B.;
King, M. A.; Gale, P.A.; Essex, J. W. J. Am. Chem. Soc. 2002, 124, 8644.

11) (a) Sessler, J. L.; Camiolo, S.; Gale, P.A. Coord. Chem. Rev. 2003, 240, 17. (b) Llinares, J.
M.; Powell, D.; Bowman-James, K. Coord. Chem. Rev. 2003, 240, 57. (c) Bondy, C. R.;
Loeb, S. J. Coord. Chem. Rev. 2003, 240, 77. (d) Choi, K.; Hamilton, A. D. Coord. Chem.
Rev. 2003, 240, 101. (e) Lamber, T. N.; Smith B. D.; Coord. Chem. Rev. 2003, 240, 129.
(f) Davis, A. P.; Joos, J.-B. Coord. Chem. Rev. 2003, 240, 143.

12) Lehn, J. Supramolecular Chemistry; VCH Weinheim, 1995.

13) Lohr, H.; Vogtle, F. Acc. Chem. Res. 1985 18, 65.

14) Czamik, M. Acc. Chem. Res. 1994. 27, 302.

15) Bowman-James, K. Acc. Chem. Res. 2005, 38, 671.









16) For example: (a) Melaimi, M.; Gabbai, F. P. J. Am. Chem. Soc. 2005, 127, 9680. (b)
Cottone, A.; Scott, M.J. Organometallics 2000, 19, 5254. (c) Katz, H. J. Org. Chem.
1985, 50, 5027. (d) Katz, H. J. Am. Chem. Soc. 1986, 108, 7640. (e) Tamao, K.; Hayashi,
T.; Ito, Y. J. Organomet. Chem. 1996, 506, 85. (f) Williams, V.; Piers, W.; Clegg, W.;
Elsegood, M.; Collins, S.; Marder, T. J. Am. Chem. Soc. 1999, 121, 3244. (g) Sole, S.;
Gabbai, F.P.; Chem Commun. 2004, 11, 1284. (h) Chaniotakis, N.; Jurkschat, K.; Miller,
D.; Perdikaki, K.; Reeske, G. Eur. J. Inorg. Chem. 2004, 11, 2283.

17) For example: (a) Anzenbacher, P.; Jursikova, K.; Sessler, J. J. Am. Chem. Soc. 2000, 122,
9350. (b) Woods, C.; Salvatore, C.; Light, M. E.; Coles, S. J.; Hursthouse, M. B.; King, M.
A.; Gale, P.A. Essex, J. W. J. Am. Chem. Soc. 2002, 124, 8644. (c) Kang, S. O.;
VanderVelde, D.; Powell, D.; Bowman-James, K. J. Am. Chem. Soc. 2004, 126, 12272.

18) Moyer, B.; Bonnesen, P. in Supramolecular Chemistry ofAnions, ed. A. Bianchi, K.
Bowman-James, K. Garica-Espana and E. Garcia-Espana. Wiley-VCH, New York, 1997,
pp.1-44.

19) Jeffrey, G. An Introduction o Hydrogen Bonding; Oxford Universities Press: New York,
1997.

20) Desiraju, G. Acc. Chem. Res. 2002. 35, 565.

21) Pauling, L. The Nature of the Chemical Bond. Cornel University Press: Ithica, New York,
1939.

22) Kubik, S.; Reyheller, C.; Stuwe, S.; J. Incl. Phenom. Macroc. Chem. 2005, 52, 137.

23) Park, C.; Simmins, H. J. Am. Chem. Soc. 1968. 90, 2431.

24) Graf, E.; Lehn, J. J. Am. Chem. Soc. 1976. 98, 6403.

25) Lehn, J.; Sonveaux, E.; Willard, A. J. Am. Chem. Soc. 1978. 100, 4914.

26) Dietrich, B.; Lehn, J.; Guilhem, J.; Pascard, C. Tetrahedron Lett. 1989.30, 4125.

27) Reilly, S.; Khalsa, D.; Ford, D.; Brainard, J.; Hay, B.; Smith, P. Inorg. Chem. 1995. 34,
569.

28) Schmidtchen, F. Angew. Chem. Int. Ed. Engl. 1977. 16, 720.

29) Worm, K.; Schmidtchen, F.; Schier, A.; Schafer, A.; Hesse, M. Angew. Chem. Int. Ed.
1994. 33,327.

30) Bauer, V.; Clive, D.; Dolphin, D.; Paine, J.; Harris. F.; King, M.; Loder, S.; Wang, W.;
Woodward, R. J. Am. Chem. Soc. 1983. 105, 6429.

31) Sessler, J.; Cyr, M.; Lynch, V.; McGhee, E.; Ibers, J. J. Am. Chem. Soc. 1990. 112,
2810.









32) Sessler, J.; Cyr, M.; Furuta, H.; Kral, V.; Mody, T.; Morishima, T.; Shionoya, M.;
Weghorn, S. Pure Appl. Chem. 1993. 65, 393.

33) Dietrich, B. Pure Appl. Chem. 1993. 7, 1257.

34) Schmidtchen, F.; Tetrahedron Lett. 1989. 30, 4493.

35) Valiyaveettil, S.; Engbersen, F.; Verboom, W.; Reinhoudt, D. Angew. Cehm. Intl. Ed.
1993.32, 900.

36) Gale, P. Coor. Chem Rev. 2003. 240, 191.

37) Kang, S.; Llinares, J.; Powell, D.; VanderVelde, D.; Bowman-James, K. J. Am. Chem.
Soc. 2003. 125, 10152.

38) Katz, H. in Inclusion Compounds. Atwood, J.; Davies, J.; MacNicol, D. Oxford
University Press Publishers, Oxford, 1991. Vol 4, Chapter 9, pp. 391-405.

39) Rudkevik, D.; Verboom, W.; Reinhoudt, D. J. Org. Chem. 1994. 59, 3683.

40) D. M. Rudkevich, W. Verboom, Z. Brzozka, M. J. Palys, W. P. R. V. Stauthhamer, G.J.
van Hummel, S. M. Fraken, S. Harkema, J. F. J. Engbersen and D. N. Reinhoudt, J. Am.
Chem. Soc. 1994. 116, 4341.

41) (a) White, D.; Laing, N.; Miller, H.; Parsons, S.; Coles, S.; Tasker, P. Chem. Commun.
1999. 2077. (b) Miller, H.; Laing, N.; Parsons, S.; Parkin, A.; Tasker, P. J. Chem. Soc.
Dalton Trans. 2000. 3773.

42) (a) Vermersch, P.; Lemon, D.; Tesmer, G.; Quiocho, F. Biochemistry. 1991. 30, 6861.
(b) Vyas, N.; Vyas, M.; Quiocho, F. Science. 1988. 242,1290. (c) Spurlino, J.; Lu, G.;
Quiocho, F. J. Biol. Chem. 1991. 266, 5202.

43) Smith, D. Org. Biol. Chem. 2003. 1, 3874.

44) Zhou, G.; Cheng, Y.; Wang, L.; Jing, X.; Wang, F. Macromolecules. 2005. 38, 2148.

45) Dinger, M.; Scott, M. J. Eur. J Org. Chem. 2000, 2467. Dinger, M.; Scott, M. J. Chem.
Commun. 1999, 2525.

46) For example: (a) Turner, D. R.; Spencer, E. C.; Howard, J. A. K.; Tocher, D. A.; Steed,
J. W. Chem. Commun. 2004, 1352. (b) Bondy, C. R.; Gale, P. A.; Loeb, S. J. J. Am.
Chem. Soc. 2004, 126, 5030. (c) Beer, P. D.; Hayes, E. J. Coord. Chem. Rev. 2003, 240,
167.

47) (a) Dutzler, R.; Campbell, E. B.; MacKinnon, R. Science 2003, 300, 108. (b) Dutzler,
R.; Campbell, E.; Cadene, M. ; Chait, B.; MacKinnon, R. Nature, 2002, 415, 287.









48) (a) Kolbe, M.; Besir, H.; Essen, L. O.; Oesterhelt, D. Science 2000, 288, 1390. (b)
Facciotti, M. T.; Cheung, V. S.; Lunde, C. S.; Rouhani, S.; Baliga, N. S.; Glaeser, R. M.
Biochemistry 2004, 43, 4934.

49) For a review of sulphate and phosphate binding sites see: Copley, R. R.; Barton, G. J.; J.
Mol. Biol. 1994, 242, 321.

50) Channa, A.; Steed, J. W.; J. Chem. Soc. Dalton Trans. 2005, 2455. Ghosh, S.;
Choudhury, A. R.; Row, T. N. G.; Maitra, U. Org. Lett. 2005, 7, 1441. Zhou, G.; Cheng,
Y.; Wang, L.; Jing, X.; Wang, F. Macromolecules, 2005, 38, 2148. Smith, D.; Org.
Biomol. Chem. 2003, 1, 3874. Lee, K. H.; Lee, H. Y.; Lee, D. H.; Hong, J. I.
Tetrahedron Lett. 2001, 42, 5447.

51) Kondo, S. I.; Suzuki, T.; Toyama, T.; Yano, Y. Bull. Chem. Soc. Jpn. 2005, 78, 1348.
Hiratani, K.; Sakamoto, N.; Kameta, N.; Karikomia, M.; Nagawa, Y. Chem. Commun.
2004, 1474. Miyaji, H.; Sessler, J. L.; Angew. Chem. Int. Ed. 2001, 40, 154. Jeong, K.
S.; Hahn, K. M.; Cho, Y. L. Tetrahedron Lett. 1998, 39, 3779. Davis, A. P.; Gilmer, J.
F.; Perry, J. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 1312. Beer, P. D.; Dent, S. W.;
Wear, T. J. J. Chem. Soc. Dalton Trans. 1996, 2341.

52) Antonisse, M. M. G.; Reinhoudt, D. N. Chem Commun. 1998, 443. Plieger, P. G.;
Tasker, P. A.; Galbraith, S. G. J. Chem. Soc. Dalton Trans. 2004, 313.

53) Cottone, A.; Morales, D.; Lecuivre, J. ; Scott, M. J. Organometallics. 2002, 21, 418.

54) de Castro, B.; Ferreira, R.; Freire, C.; Garcia, H.; Palomares, E. J. ; Sabater, M. J. New.
J. Chem. 2002, 26, 405.

55) Shimazaki, Y.; Tani, F.; Fukui, K.; Naruta, Y.; Yamauchi, 0. J. Am. Chem. Soc. 2003,
125, 10512.

56) Kang, S.; Llinares, J.; Powell, D.; VanderVelde, D.; Bowman-James, K. J. Am. Chem.
Soc. 2003, 125, 10152.

57) Shionoya, M.; Furuta, H.; Lynch, V.; Harriman, A.; Sessler, J. J. Am. Chem. Soc. 1992,
114, 5714.

58) Kang, S. O.; VanderVelde, D.; Powell, D.; Bowman-James, K. J. Am. Chem. Soc. 2004,
126, 12272.

59) Bourson, J.; Pouget, J.; Valeur, B.; J. Phys. Chem. 1993, 97 4552.

60) With help from Chase Rainwater on computer program

61) Lai, C.; Mak, W.; Chan, E.; Sau, Y.; Zhang, Q.; Lo, S.; Williams, I.; Leung, W. Inorg.
Chem. 2003, 42, 5863.

62) Zhou, X.; Huang, J.; Yu, X.; Zhou, Z.; Che, C. J. Chem. Soc. Dalton Trans. 2000, 7, 1075.









63) Libra, E.; Scott, M. Chem Commun. 2006. 1485.

64) Campbell, E.; Nguyen, S. Tett. Lett. 2001. 42, 1221.

65) Synthesis developed by Melanie Veige

66) Etter, M.; Urbanczyk-Lipkowska, Z.; Zia-Ebrahimi, M.; Pununto, T. J. Am. Chem. Soc.
1990. 112, 8415.

67) Gale, P. Coor. Chem. Rev. 2003. 240, 191.

68) Kelly, T.; Kim, M. J. Am. Chem. Soc. 1994. 116, 7072.

69) Snellink-Ruel, B.; Antonisse, M.; Engberson, J.; Timmerman, P.; Reinhoudt, D. Eur. J.
Org. Chem. 2000. 165.

70) (a) Turner, D.; Paterson, M.; Steed, J. J. Org. Chem. 2006. 71(4), 1598. (b) Oh, J.; Cho,
E.; Ryu, B.; Lee, Y.; Nam, K. Bull. Korean Chem. Soc. 2003. 24, 10.

71) Bondy, C.; Gale, P.; Loeb, S. J. Am. Chem. Soc. 2004, 126, 5030.

72) Bordwell, F. Acc. Chem. Res. 1988, 21, 456.

73) Nishizawa S.; Buhlmann P.; Iwao M.; Umezawa Y. Tetr. Lett. 1995, 36, 6483.

74) Gomez, D.; Fabbrizzi, L.; Licchelli, M.; Monzani, E. Org. Biomol. Chem. 2005, 3,
1495.

75) Boiocchi, M.; Del Boca, L.; Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M.; Monzani,
E. Chem. Eur. J. 2005, 11, 3097.

76) Amendola, V.; Boiocchi, M.; Colasson, B.; Fabbrizzi, L. Inorg. Chem. 2006, 45(16),
6138.

77) Shimazaki, Y.; Tani, F.; Fukui, K.; Naruta, Y. ; Yamauchi, O. J. Am. Chem. Soc. 2003,
125, 10512.

78) Mizukami, S.; Houjou, H.; Kanesato, M.; Hiratani, M. Eur. J. Chem. 2003. 9(7), 1521.

79) Cozzi,P. Chem Soc. Rev. 2004,33,410.

80) Baleizao, C.; Garcia, H. Chem. Rev. 2006, 106, 3987.

81) Jocabson, E.; Zhang, W.; Muci, A.; Ecker, A.; Deng, J. J. Am.Chem. Soc. 1991, 113,
7063.

82) Schaus, S.; Branalt, J.; Jacobson, E. J. Org. Chem. 1998, 63, 403.









83) (a) Saito, B.; Katsuki, T. Tetrahedron Lett. 2001, 42, 3873. (b) Li, Z.; Conser, K. R.;
Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326. (c) Martinez, L. E.; Leighton, J. L.;
Carsten, D. H.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5897.

84) Katsuki, T. Synlett. 2003, 281.

85) Samsel, E.; Srinivasan, K. Kochi, J. J. Am. Chem. Soc. 1985, 107, 7606.

86) Srinivasan, K.; Michaud, P.; Kochi, J. J. Am. Chem. Soc. 1986, 108, 2309.

87) For example: Collin, J.; Daran, J.; Schulza, E.; Trifonov, A. Chem. Commun. 2003,
3048.

88) For examples: Zhang, W.; Loeban, J.; Wilson, S.; Jacobson, E. J. Am. Chem. Soc. 1990,
112(7), 2801.

89) Fukuda, T.; Irie, R.; Katsuki, T. Synlett. 1995, 197.

90) Yamamoto, H.; Susumu, S. Pure & Appl. Chem. 1999, 71(2) 239.

91) Corey, E.; Huzman-Perez, A. Angew. Chem. Int. Ed. 1998, 37, 388.

92) Dias, L. Current Org. Chem. 2000, 4, 305.

93.) Cozzi, P.; Papa, A.; Umani-Ronchi, A. Tett. Lett. 1996, 37(26), 4613.

94) DiMauro, E.; Kozlowski, M. Org. Lett. 2001, 3(19), 3053.

95) (a) Garcia, C. ; LaRochelle, L.; Walsh, P. J. Am. Chem. Soc. 2002, 124, 10970. (b)
DiMauro, E.; Kozlowski, M. J. Am. Chem. Soc. 2002, 124, 12668.

96) Cozzi, P. Angew. Chem. Int. Ed. 2003, 42, 2895.

97) Corey, E. Angew. Chem. Int. Ed. 2002, 41, 1650.

98) Ahrendt, K.; Borths, C.; MacMillan, D. J. Am. Chem. Soc. 2000, 122, 4243.

99) Chapman, J.; Day, C.; Welker, M. Organometallics. 2000, 19(9), 1615.

100) Takenaka, N.; Huang, Y.; Rawal, V. Tetrahedron. 2002, 58, 8299.

101) Yamamoto, H.; Futatsugi, K. Angew. Che. Intl. Ed. 2005, 44, 1924.

102) Chang, K.; Huang, C.; Liu, Y.; Hu, Y.; Chou, P.; Lin, Y. Dalton Trans. 2004, 1731.

103) (a) Morris, G.; Zhou, H.; Ster, C.; Nguyen, S. Inorg. Chem. 2001, 40, 3222. (b)
Korupoju, S.; Mangayarkarasi, N.; Ameerunisha, S.; Valente, E.; Zacharias, P. Dalton
Trans. 2000, 2845. (c) Szlyk, E.; Wojtczak, A.; Surdykowski, A.; Gozdzikiewicz, M.
Inorg Chem Acta, 2005, 358, 467.









104) (a) Gao, J.; Reibenspies, J. H.; Zingaro, R. A.; Woolley, F. R.; Martell, A. E.; Clearfield,
A. Inorg. Chem. 2005, 44(2), 232. (b) Huang, W.; Gou, S.; Hu, D.; Chantrapromma, S.;
Fun, H.-K.; Meng, Q. Inorg. Chem. 2001, 40(7), 1712.

105) Chen, G.; Zhai, B.; Sun, M.; Qi, W.; Acta Crystallogr. E. 2005, 61, m1869.

106) Wiznycia, A.; Desper, J.; Levy, C.; Chem. Commun. 2005, 37,4693.

107) Bunge, J.; Boyle, T.; Pratt, H.; Alam, T.; Rodriguex, M. Inorg. Chem. 2004, 6035.

108) (a) Bunge, S. D.; Boyle, T. J.; Pratt, H. D., III; Alam, T. M.; Rodriguez, M. A.
Inorg. Chem. 2004 43(19); 6035. (b) Chisolm, M.; Huang, J.; Huffman, T.; Streib, W.;
Tiedtke, D. Polyhedron, 1997, 16, 2941.

109) (a) Gambarotta, S.; Arena, F.; Floriani, C.; Zanazzi, P. J. Am. Chem. Soc. 2000, 122,
8946. (b) Schaus, S.; Brandes, B.; Larrow, J.; Tokunaga, M.; Hansen, K.; Gould, A.;
Furrow, M.; Jacobsen, E. J. Am. Chem. Soc. 2002, 124, 1307.

110) Uchida, T.; Katuski, T.; Ito, K.; Akashi, S.; Kuroda, T. Helvetica ChimicaActa. 2002,
85, 3078.

111) Shen, Y.-M.; Duan, W.-L.; Shi, M. J. Org. Chem. 2003 68(4), 1559.

112) Lindoy, L.; Meehan, G.; Svenstrup, N. Synthesis. 1998, 7, 1029.









BIOGRAPHICAL SKETCH

Eric Libra was born in Erie, Pennsylvania in 1980. His love for science began at an early

age and an interest in chemistry began while at General McLane High school, where he

graduated as valedictorian in 1998. He earned a B.S. in chemistry from Boston College in 2002

where he worked in Professor William Armstrong's research group, which was his first exposure

to inorganic chemistry. Eric began his graduate studies at the University of Florida in 2003

where he joined Professor Michael Scott's group. Upon completion of his Ph.D, Eric will join

Adesis Inc. in New Castle, Delaware as a synthetic chemist.





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1 METAL SALEN COMPLEXES IN ANION BINDING AN D CATALYSIS By ERIC R. LIBRA A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLOR IDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2007

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2 2007 Eric R. Libra

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3 To Caroline and my parents and my entire family

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4 ACKNOWLEDGMENTS Although I am unaware of when I made the decision to become a chemist, I know my interest in science and discovery has been in place sin ce an early age. As a young child I always had an interest in dinosaurs and astronomy, but the person who may just have steered me in the direction of chemistry was Mr. Wizard. Watchi ng his program led me to want to perform experiments at home and also stoked my desire for my first chemistry set. There are many people who have helped me reach this point not only as a chemist but also as a person and I would like to thank them for all they have done. I owe a dept of gratitude to my parents, Dennis and JoAnne Libra, who have been instrumental in my life. I would not be in the po sition I am in now if it was not for them. They always put their children and our ed ucations first and whether it was driving us to soccer practice or piano lessons or making the financial sacrific es so that my brothers and I could attend the colleges of our choosing, they have been self less through it all. I thank my younger brothers, Broc and Garrett, for the fun times growing up a nd for taking all the abuse a big brother dishes out, as well as not giving it back to me too much when you both outgrew me and I was the little brother. I thank my grandparents, J ohn and Bertha Kowalczyk, who help raise me as well as my grandparents, Peter and Cecelia Li bra for the Sunday after noon spaghetti dinners. Three professors have had a tremendous impact on my life and have guided me to where I am today. Dr. William Armstrong at Boston Colleg e was the first professor to give me the opportunity to work in a research environment, and this positive experience is what made me decide to attend graduate school. He was also instrumental in he lping me pick a graduate school and I eventually realized that the University of Florida and the Scott Group was the place where I belonged. My two plus years working in the X-Ray lab at the University of Florida, were very rewarding and I have Dr. Khalil Abboud to thank for that. Khalil was always there to talk and to

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5 give advice on chemistry and many other subjects I thoroughly enjoyed my time working with him and it was nice to have a few hours a day to be able to concentrate on topics other than synthesis. Most importantly, I would like to thank my advisor Dr. Michael Scott. Mike was responsible for my being at UF, and I hope that I have proven that his decision to bring me here was the right one. Since my arrival in Gainesville he has been a great mentor and I think that my chemical knowledge and intuition has exponentially increased since my arrival. He always was able to make a helpful suggestion when I hit a wall, and I was always ecstatic when it worked. He is one of the rare professors that has f ound the perfect median be tween giving the students enough space to figure things out for themselv es, yet involved enough so students have a direction and a goal. Many other people made my time here more en joyable. I would like to thank my lab mates Ivanna, Hue, Nella, Ranjan, Ozge, Canda ce, Melanie, Patrick, Nate, Gary, Nicolas, Dempsy and Anna, among many other short term visitors, from whom I have learned many practical aspects of chemistry in cluding many tricks of the trade. I had the pleasure of working with a great undergraduate, Nate Strutt, and I ho pe I did not teach him too many bad habits these last two years. A special thanks goes out to my lab mate Candace and pseudo lab mate Justin for making inorganic chemistry fun, from classes, to cume s, to orals, to the years of research. They were always there together to ta lk sports or get a drink at Gato r City to take out minds off the tasks at hand. I am sure my graduate experi ence would not have been as enjoyable without them. Another thanks goes to James and the entire Quarter Barrel Saturday crew. It was definitely the most enjoyable part of my last f our years in Gainesville and even if it was only a few Saturday afternoons a year it was much needed in order to maintain our sanity.

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6 Most importantly, I would like to thank my wife to be Caroline. I moved to Gainesville with many mixed feelings, as I knew it would be se veral years we would not be together. Being apart for so long has been tremendously difficult a nd I can not wait to be b ack together and share our lives once again. I could not have done this without her love, encouragement and especially her patience with me and our situation.

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7 TABLE OF CONTENTS page ACKNOWLEDGMENTS...............................................................................................................4 LIST OF TABLES................................................................................................................. ........10 LIST OF FIGURES................................................................................................................ .......11 ABSTRACT....................................................................................................................... ............15 CHAPTER 1 INTRODUCTION..................................................................................................................16 Anion Coordination Modes....................................................................................................17 Initial Studies of Anion Receptor Systems.............................................................................18 Pyrrolic Macrocycle Receptors...............................................................................................19 Biologically Relevant Receptors In corporating the Guanidinium Group..............................20 Neutrally Charged Receptors..................................................................................................20 Anion Coordination Through Lewis Acidic Metals...............................................................21 Hydrogen Bonding Interactions Through Oxygen Donors....................................................22 Research Objectives............................................................................................................ ....23 2 METAL SALEN COMPLEXES INCORP ORATING TRIPHENOXYMETHANES: EFFICIENT, SIZE SELECTIVE BINDING OF FLUORIDE WITH A VISUAL REPORT......................................................................................................................... ........28 Introduction................................................................................................................... ..........28 Results and Discussion......................................................................................................... ..28 Advantages of the Salen Macrocycle..............................................................................29 Design of Receptor System.............................................................................................29 Anion Binding Properties................................................................................................31 Binding Constants...........................................................................................................33 Solid State Structure of [2-2-F]1-.....................................................................................34 Anion Binding Studies for 2-3........................................................................................34 Conclusions.................................................................................................................... .........35 Experimental Methods........................................................................................................... .36 General Considerations...................................................................................................36 Synthesis of 2-1...............................................................................................................36 Synthesis of R R -2-1........................................................................................................37 Synthesis of R R -2-2........................................................................................................37 Synthesis of 2-2...............................................................................................................38 Synthesis of 2-3...............................................................................................................38 Synthesis of [2-2-F](Bu4N).............................................................................................39 Determination of binding constants (LogKs)...................................................................39

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8 3 A SYNTHETIC MODEL OF THE CLC CHLORIDE ION CHANNEL; A STRUCTURAL AND ANION BINDING STUDY..............................................................52 Introduction................................................................................................................... ..........52 Results and Discussion......................................................................................................... ..53 Salens as Anion Receptors..............................................................................................53 Synthesis of a Mixed Salen Receptor..............................................................................54 Anion Coordination and Binding Constants....................................................................56 Solid State Structure........................................................................................................57 Conclusions.................................................................................................................... .........57 Experimental Methods........................................................................................................... .58 General Considerations...................................................................................................58 Determination of binding constants (LogKs)...................................................................58 Synthesis of 3-1...............................................................................................................58 Synthesis of 3-2..............................................................................................................59 Synthesis 3-3.................................................................................................................. .60 Synthesis of 3-4...............................................................................................................61 Synthesis of 3-5...............................................................................................................61 Synthesis of 3-6...............................................................................................................62 Synthesis of 3-7...............................................................................................................63 Synthesis of 3-8...............................................................................................................63 4 METAL SALEN UREA COMPLEXES AND THEIR HIGH AFFINITIES FOR THE HALIDES........................................................................................................................ .......69 Introduction................................................................................................................... ..........69 Results and Discussion......................................................................................................... ..70 Conclusions.................................................................................................................... .........79 Experimental Methods........................................................................................................... .80 General Considerations...................................................................................................80 Synthesis of 4-2...............................................................................................................81 Synthesis of 4-3...............................................................................................................81 Synthesis of 4-6...............................................................................................................82 Synthesis of 4-7...............................................................................................................82 Synthesis of 4-8...............................................................................................................82 5 DESIGNER LEWIS ACIDS; THE DEVELO PMENT OF EXREMELY BULKY AND RIGID DINUCLEAR CHIRAL CATALYSTS.....................................................................99 Introduction................................................................................................................... ..........99 Jacobsens Catalyst..........................................................................................................99 Lewis Acid Catalysts.....................................................................................................100 Zn Salens in Catalysis...................................................................................................100 The Promotion of the Diels-Al der Reaction by a Lewis Acid......................................102 General Approaches of Synthetic Design......................................................................102 Results and Discussion.........................................................................................................102 Binap Ligand.................................................................................................................103

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9 Racemic Zn Catalyst......................................................................................................104 Chiral Zn Catalyst..........................................................................................................107 Co Catalysts...................................................................................................................107 Low Solubility Chiral Ligands......................................................................................108 Initial Catalysis Studies.................................................................................................109 Conclusions.................................................................................................................... .......109 Experimental Methods..........................................................................................................110 General Considerations.................................................................................................110 Synthesis of 5-2.............................................................................................................110 Synthesis of 5-3.............................................................................................................111 Synthesis of 5-4.............................................................................................................111 Synthesis of 5-5.............................................................................................................112 Synthesis of 5-6.............................................................................................................112 Synthesis of 5-7.............................................................................................................113 Synthesis of 5-8.............................................................................................................113 Synthesis of 5-9.............................................................................................................114 Synthesis of racemic 5-10.............................................................................................114 Synthesis of 5-11...........................................................................................................115 Synthesis of 5-12...........................................................................................................115 Synthesis of 5-13...........................................................................................................116 Synthesis of 5-14...........................................................................................................116 Synthesis of 5-15...........................................................................................................117 Synthesis of 5-16...........................................................................................................117 Synthesis of 5-17...........................................................................................................117 LIST OF REFERENCES.............................................................................................................133 BIOGRAPHICAL SKETCH.......................................................................................................140

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10 LIST OF TABLES Table page 2-1 X-ray data for the crystal stru ctures of 2-1 and the complexes R R -2-1, 2-3, and 2-2F.............................................................................................................................. ...........40 4-1 LogKs values of the two salen urea complexes with fluoride, chloride and bromide in acetone........................................................................................................................ .......84 4-2 X-ray data from crystal stru ctures of 4-2, 4-3, 4-4, 4-6, 4-8..............................................84

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11 LIST OF FIGURES Figure page 1-1 Structure of Park and Simons katapi nate; the first example of an anion binder..............24 1-2 Structure of azacryptand that is an ideal size match for fluoride.......................................24 1-3 Structure of zwitteri onic neutral receptor. ........................................................................24 1-4 Structure of the pyrro lic macrocycle sapphyrin. ..............................................................25 1-5 Structure of two bicyclic guani diniums attached by a urethane linker..............................25 1-6 Structure of ne utral anion receptor....................................................................................26 1-7 Structures of amide ba sed receptors by Bowman-James...................................................26 1-8 Structure of salen complex with ur anyl used for Lewis acidic anion binding...................27 1-9 Structure of conjugated polymer th at efficiently binds fluoride though phenols..............27 1-10 Structure of triphenoxymethane platform..........................................................................27 2-1 Open conformation of ClC chloride channel.....................................................................40 2-2 Triphenoxymethane platform with the phenols in the all up position re lative to the methine carbon hydrogen...................................................................................................41 2-3 Procedure used for the synthesis of 21, macrocycle metalation to form 2-2, and 2-3 and fluoride binding...........................................................................................................41 2-4 Solid-state structure of 2-1............................................................................................. ....42 2-5 Solid-state structure of 2-2............................................................................................. ....43 2-6 Solid-state structures of 2-3............................................................................................ ...44 2-7 1H NMR spectrum of 2-3 (top) and [2-3-F]1(bottom) taken in d6-DMSO with an inset of the 19F NMR spectrum of [2-3-F]1in the region of bound fluoride.....................45 2-8 1H NMR spectrum of 2-2...................................................................................................45 2-9 1H NMR spectrum of 2-2 with 0.5 e quivalents of fluoride added.....................................46 2-10 1H NMR spectrum of 2-2 with one equi valent or more of fluoride...................................46 2-11 UV-Vis titration of 22 with tetra-butylammonium fluoride in acetone. ........................47

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12 2-12 Job plot of the titration of 2-2 with tetrabutylammonium fluoride....................................47 2-12 Absorbance plotted versus concentration of fluoride for the titration of 2-2 at 450nm with tetrabutylammonium fluoride....................................................................................48 2-14 Crystal structure of [2-2-F]1with fluoride bound in the phenolic pocket.........................49 2-15 UV-Vis titration of 2-3 salen with te tra-butylammonium fluoride in acetone..................50 2-16 Job plot from UV-Vis spectra titrat ion data of 2-3 in acetone with tetrabutyammonium fluoride.....................................................................................................50 2-17 Absorbance plotted versus concentration of fluoride for the titration of 2-3 complex at 450 nm with tetrabut ylammonium fluoride...................................................................51 3-1 Open conformation of ClC chloride channel.....................................................................64 3-2 Compound [2-2-F]with a fluoride hydrogen bonding with the four phenols of the anion receptor................................................................................................................. ....64 3-3 Structure of salen based anion receptor with amine groups at the periphery. The receptor coordinates bot h cations and anions....................................................................65 3-4 Synthetic scheme for Compound 3-5.................................................................................65 3-5 Synthetic scheme for the synthesis of mixed phenolic-urea salen system (3-7), metalation at salen binding site and anion coordination (3-8)...........................................66 3-6 Titration plot of 3-7 with fluoride......................................................................................67 3-7 Depiction of the soli d-state structure of [3-8-Cl]-..............................................................68 4-1 Proposed structure and binding mode of an early urea based anion receptor....................85 4-2 Structure of an urea subunit where the anion binding cavity is regulated by metal coordination................................................................................................................... ....85 4-3 Synthetic scheme for the formation of salen urea (4-1).....................................................86 4-4 Solid-state structure of 4-2.............................................................................................. ...86 4-5 Solid-state structure of 4-3.............................................................................................. ...87 4-6 UV-Vis titration of 42 with tetra-butylammonium fluoride in acetone............................88 4-7 Binding constant data of 4-2 titrated with Fat 450nm.....................................................89 4-8 Solid-state structure of 4-4.............................................................................................. ...90

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13 4-9 Job plot of 4-2 for chloride............................................................................................. ...91 4-10 Solid-state structure of 4-5............................................................................................. ....92 4-10 UV-Vis titration of 4-2 with tetrabutylammonium chloride in acetone...........................93 4-12 Binding constant data of 4-2 titrated with Clat 450nm Log Ks = 5.27..........................94 4-13 Synthetic scheme for compound 4-6. ................................................................................77 4-14 Depiction of the soli d-state structure of 4-6......................................................................96 4-15 Synthesis of ligand 4-7 and C3 symmetric anion receptor 4-8...........................................97 4-16 Depiction of the soli d-state structure of 4-8......................................................................98 5-1 Structure of Jacobsens catalyst used for the asymmetric epoxidation of olefins...........119 5-2 Proposed mechanism for the epoxidati on of olefins with Jacobsens catalyst................119 5-3 Structure of catalyst with chiral binapthyl groups that influence the geometry of the substrate...................................................................................................................... .....120 5-4 Reaction scheme for the ethyl addition to benzaldehyde.................................................120 5-5 Structure of a bifunctional catalyst containing both a Lewis acid and Lewis base component...................................................................................................................... ..120 5-6 Enantioselective alkynation of ketones............................................................................121 5-7 Proposed transition state for the alkynati on of ketones with a zinc salen catalyst..........121 5-8 Diels-Alder reaction be tween cyclopentadiene and cinnamaldehyde promoted by a Lewis acid catalyst...........................................................................................................121 5-9 Solid state structure of compound 2-2. ..........................................................................122 5-10 Depiction of 2,2-diamino-1,1-binapthaly ene showing the large torsion angle between the two napthyl planes.....................................................................................................122 5-11 Synthetic scheme for the synthesis of 5-2........................................................................123 5-12 Synthetic scheme for the formation of 5-4. ....................................................................123 5-13 Solid state structure of compound 5-4.............................................................................124 5-14 Solid state structure of 5-6............................................................................................ ...125 5-15 Solid state structure of compound 5-7.............................................................................126

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14 5-16 Solid state structure of the dinuclear catalyst 5-8. ..........................................................127 5-17 Space filling model of the solid state structure of 5-8.....................................................128 5-18 1H NMR spectrum of the paramagnetic compound 5-9...................................................128 5-19 Solid state structure of the dinuclear compound 5-10.....................................................129 5-20 Schematic of triphenoxymethane aldehyde showing its possible positions for ligand modification................................................................................................................... ..129 5-21 Synthetic scheme for compounds 5-11 and 5-12.............................................................130 5-22 Synthetic scheme for th e synthesis of 5-13 and 5-14......................................................130 5-23 Schematic diagram of the structures of 5-15, 5-16, and 5-17..........................................131 5-24 Crystal structure of 5-16; Co (II) is arranged in an octahedral geometry.......................131 5-25 Catalytic reaction of the ethyl addition to benzaldehyde us ed as a standard to monitor the catalytic ability of the compounds.............................................................................132

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15 Abstract of Dissertation Pres ented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy METAL SALEN COMPLEXES IN ANION BINDING AN D CATALYSIS By Eric R. Libra August 2007 Chair: Michael J. Scott Major: Chemistry Most forms of life require the recognition and transportation of anions. There have been numerous efforts to develop synthetic receptor sy stems that are both efficient and selective for the coordination of anions. Nature often empl oys the use of OH groups for anion coordination, yet this binding mode is one that has not been explored in the area of synthetic anion receptor design. A series of substituted metal salen co mpounds have been developed that show a high affinity for the coordination of anions. The ri gid metal salen macrocycle can orientate four phenol groups into a tetrahedral array that tightly and selectivel y binds fluoride through four strong OH-F hydrogen bonding interactions. The size of the anion bi nding cavity can be regulated by the incorporation of different metal centers, enabling the properties of the system to be modified. Metals also offer convenient path ways to report the bi nding event via spectral changes from the strong metal to ligand charge transfer transitions, making these receptors anion sensors. Not only can the metal salen system organize groups for anion binding, they can also be used as chiral catalysts. The synthesis of a rigid and sterically bulky metal salen complex has been undertaken for the use as an asymmetric catalyst to promote organic transformations.

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16 CHAPTER 1 INTRODUCTION Anions are ubiquitous in a variety of chemical and biological systems.1 For complex forms of life to exist, many biochemical proce sses require the recogniti on and transportation of anions.2 A number of enzyme substrate interactions rely on anions and it is reported that anions exist in about 70% of all enzymatic sites wher e they play a key role in enzyme substrate interactions, as well as having importa nt structural roles in proteins.2 The malfunction of channels that facilitate anions acros s cell membranes, especially chloride,3 is considered the primary cause of many diseases including cystic fibrosis,4 Bartters syndrome,5 Dents disease,6 Pendreds syndrome,7 and osteopetrosis.8 Over the last 25 years there have been nume rous efforts to create systems for anion coordination.9 The development of selective anion r eceptors is difficult compared to those designed for selective cation complexation, as anions are typically larger th an their isoelectronic cationic counterparts and thus typically have a more diffuse charge. Solvent and pH concerns also play major roles in anion complexation a nd the nature of coordinating solvents often regulates anion binding and selec tivity. Captions are able to form covalent or dative bonds readily to receptor systems while anions must rely on weaker electrostatic forces such as hydrogen bonding or Lewis acidic interactions.10 There are many examples of anion recogniti on by host molecules containing various structural and binding modes.11 Some of these systems are ab le to signal the binding event, which is often done by incorporating various substitu ents that have the ab ility to report the anion coordination process.12 Some sensors display a cha nge in color or fluorescence upon interaction with anions, and the ab ility to readily detect the bindi ng event has recently become an important aspect of anion receptor design.13,14 The ability to determine on the macroscopic level

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17 what is happening at the molecular level, such as the coordination of an anion guest into a host molecule may lead to the qualitative and/or qualitative sensing of certain guest molecules.1 Although there has been much work done in the field of anion binding; the area of anion sensing is far less explored. Anion Coordination Modes The creation of molecules that coordinate anions is consider ed to be in the realm of supramolecular chemistry.15 The interactions in volved in these systems are between molecular or ionic molecules and a guest an ion which exist without the forma tion of covalent bonds. Most of the effort to design anion receptors has focused on the use of Lewis acidic metals16 or organic ligands that employ hydrogen bonding or electrostatic interactions.17 Hydrogen bonding has shown to be the binding motif that best induces selectivity of a specific anion,18 as it is difficult to regulate the direction of Lewis acids, while hydrogen bond donor groups can easily be arranged in a multitude of geometries. There are many potential applications of anion sensors as they can selectively recognize a large variety of anions ranging from fluoride to DNA.1,9, 17 Hydrogen bonds are common in chemical syst ems as they often have an effect on molecular structure and mechanistic properties19 and are among the most well utilized means of anion coordination. A hydrogen bond is an attr active interaction betw een a hydrogen atom and an electronegative atom when the hydrogen is co valently bound to an el ectronegative donor such as oxygen or nitrogen20 and the strength and length of the hydrogen bond is influenced by the nature of both the donor and receptor atoms.21 For the design of anion receptors one must se lect the proper donor, its orientation within the molecule and also regulate the size and geom etry of the binding cavity. To provide hydrogen bond donors in a particular system, groups such as amides, amines, pyrroles, and ureas are normally used.22 N-H groups are relatively easy to preorg anize and the major ity of the current

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18 examples of anion binding systems have employed this moiety to achieve this goal. Herein, this review will briefly examine the history and progress in the field of synthetic anion receptors. Initial Studies of Anion Receptor Systems Selective anion binding has been a topic of interest for almost 40 years since the first anion binding receptor was reported in 1968 by Park and Simon, who showed that bicyclic diaza katapinands (Figure 1-1) coul d coordinate to halide ions.23 Park and Simon correctly predicted that hydrogen bonding and not the positive charge of the system was the main mode for halide complexation. Although the binding c onstants were modest with a logKs value of 2, it set the stage for an entire field of research including th at of macrocyclic ammonium based receptors. This research area began to grow in the 1970 s when Lehn began coordinating anions with polyammonium macrocycles.24 Lehns work demonstrated th at anions could be selectively coordinate based on size and the design of certain receptors and binding ca vities led to stronger interactions with certain anions For example, a receptor that was an ideal size match for chloride was developed and had a logKs value of 4 while iodide was too large to coordinate within the binding cavity and thus had a much lower binding constant. Lehn and coworkers also noted that particular receptors showed a wide range of stability constants for different anions not only of differe nt sizes, but also geom etries. An elliptical shaped receptor was designed that was selective for the linear shaped azide, while it had a low binding constant for chloride.25 The accommodation of chloride into the cavity had no geometric constraints, but it did not have the ideal fit that azide did. Due to these observations new synthetic cavities were developed with th e intention of accommoda ting certain anions by incorporating geometric and spatial constraints. The structure seen in figure 1-2 has shown to be a superb size compliment to fluoride as determined by its so lid state structure,26 and this size compatibility has led to an extr emely high binding constant of logKs = 11.2, which is 107 times

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19 larger than its binding constant for chloride.27 The strategy of creating a size and geometrically selective cavity for anion c oordination became extremely prevalent and is now a basic requirement for the design of any receptor system. Various quaternary ammonium based anion bi nders were developed that did not employ hydrogen bonding interactions, but ra ther arranged ammoniums into a cavity. By adjusting the length of the carbon linkers between the ammoni ums, the cavity size could be altered and selectivity could be affected.28 Receptors with a positive charge must contain counter ions which are in direct competition for the anion binding site s. Schmidtchen and coworkers were able to develop a zwitterionic receptor that has an overall neutral charge and avoids the problems incurred by the counter ions.29 The creation of a size selective, neutral receptor that does not employ hydrogen bonding interactions is in contrast to most other systems, yet there has been little work in this area due to synthetic challenges. Pyrrolic Macrocycle Receptors After this seminal work was introduced, the field of receptor chemistry exploded with activity. Pyrrolic macrocycles have been among the most versatile and useful molecules for anion binding, as pyrroles do not contain groups that may induce self association.1 The ease to which they can be functionalized and ability to make cyclic variations greatly increases the opportunities to tune the system and this has led to the design of pyrrolic systems of many different sizes, shapes, structur es, and electronic properties. Sapphyrins are a common pyrrolic macrocyc lic system for anion coordination30 and was first seen as an anion binder in the work of Sessler and co-workers who reported a crystal structure of a diprotona ted sapphyrin with a fluoride bound in the core.31 The initial structure with a fluoride ion coordinated was obtained accide ntally, but after this observation other anions were tested and modifications to the sapphyrin were made to tune the properties of the system.

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20 Based on the examination of the solid state stru cture of the complex, chloride was found to be too large to fit inside the center core of the receptor. Instead, tw o chloride ions were positioned and coordinated above the plane of the receptor.32 Sapphyrins are highly colored and anion coordination leads to changes in the absorption and admission spectra of the molecule, making it an anion sensor. The measurement of thes e spectroscopic changes leads to high binding constants for fluoride, chlo ride, and bromide with logKs values of 8.0, 7.2, and 6.1 respectively.32 Biologically Relevant Receptors Inco rporating the Guanidinium Group While pyrrolic macrocycles are effective anion receptors, there are many other systems that incorporate N-H groups for anion coordination. The guanidinium ion has been extensively studied because of its prevalence in nature. Guanidiniums are present in arginine residues and are responsible for many hydrogen bonding interac tions in biology. This group contains two NH hydrogen bond donors as well as a delocalized pos itive charge that contribute to its strong interactions with the guest spec ies. Guanidinium has a pKa of 13.5 which results in protonation of this moiety over a wide pH range where it wi ll retain both its posi tive charge and hydrogen bond donor properties.33 Many synthetic systems incorporating the guanidinium group, such as the molecule in Figure 1-5, have been successful anionic binders since it forms both electrostatic and hydrogen bonding interactions with anionic molecules. Neutrally Charged Receptors The presence of positive charges on a receptor system may be helpful for anion coordination, but it also leads to several problems in efficien cy and selectivity. In a charged species, it is difficult to regulate the nondirecti onal electrostatic forces, so adju stments to a particular system become more complicated. The existence of count er ions also causes problems as they are in direct competition for binding site s which affects the selectivity a nd efficiency of the receptor.1 The synthesis of neutral species eliminates many of these issues and they have proven to be

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21 amongst the best selective receptors. Reinhoudt a nd coworkers were one of the first groups to use very simple neutral host molecules as anion hosts. Figure 1-6 depicts an example of a structure that incorporates NH hydrogen bond donors to coordinate H2PO4 selectively over HSO4 and Clwith a logKs of 4.1.35 The use of N-H donors exists in numerous exam ples of simple acyclic receptor systems and small modifications have shown to e ffect anion binding ability and selectivity.36 The creation of cyclic or cage-like molecules howev er, has rigidified the molecules by placing less flexible spatial constraints on the anion. Recently Bowman-James and co-workers have developed a polyamide cryptand th at has shown to bind anions.37 Linking two sets of amides together as outlined in figure 1-7 will create a cavity with multiple N-H groups directed to wards the center. Receptor A has shown to bind strongly with phosphate and sulfate and it is be lieved that the strong interact ions are a result of the high correspondence of geometry and size between the guest and host. Amines can deprotonate the anion causing even stronger binding interactions The tren based bicyclic aza cryptands (Figure 1-7, B) are neutrally charged and have shown to bind fluoride with a hi gh efficiency. Crystal structures of the cryptand with both fluoride a nd chloride show the halid es coordinated within the central cavity and there has also been a not ed affinity for other halides as well as for H2PO4 -. Anion Coordination Through Lewis Acidic Metals Although hydrogen bonding and electro static interactions are the common modes of anion complexation, they are not the only available methods. Receptors containing Lewis acidic metals are capable of providing an anion binding site and typically incorp orate centers such as boron, silicon, mercury and tin.38 Since many anions are coordinati vely saturated the donation of electrons to a Lewis acidic metal forms a strong interaction between the two.

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22 Reinhoudt and co-workers have incorporated a uranyl in to the backbone of a salen macrocycle (Figure 1-8) and is able to coor dinate anions through th is Lewis acidic site.39 The coordination of H2PO4 occurs through both the Lewis acidic uranyl as well as a stabilizing force from the acetoamido groups.40 Salens can also act as recepto rs for Ni (II) and Cu (II) sulfate when amine groups are bound at th e periphery of the macrocycle.41 This receptor is able to coordination an anion and a cat ion into the same complex. There is great potential in the further exploration of anion receptor systems with the salen macrocycle as they provide an excellent building block for the incorporation of a variety of binding groups. The synthesis of the salen based ligands is relatively easy and a wide range of donor groups can be readily attached to the system. The incorporation of a metal center into the macrocylic rings rigidifies the structure can also make these molecules suitable for anion sensing since metal salen compounds normally exhibit st rong MLCT transitions in the visible region. The binding event can often be followed by monito ring the position of this intense absorption band. The size of the binding cavity can also be regulated by the incor poration of metals of different radii affecting the bindi ng constants for different anions. Hydrogen Bonding Interactio ns Through Oxygen Donors The use of O-H donor groups interacting with an ions in biological systems is extensive. For example, some protein recognition processe s rely on an interaction between hydroxyl groups on a carbohydrate and an anionic protein.42 In spite of the utility of hydroxyl groups in nature; almost all synthetic receptor systems use some combination of N-H groups. There have been only a handful of examples of complexes that bi nd anions with an O-H group and none of them are particularly well defined systems. The O-H group can form strong hydrogen bonding interactions but the deficiency of O-H donor examples may be due to the synthetic difficulty in preorganizing such groups. Simple, off the sh elf, phenols such as catechol can coordinate

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23 anions, although not surprisingly with rather low binding constants.43 Since then only a handful of other systems incorporating O-H donors have been developed including the work by Wang and coworkers who have created a conjugated poly mer system that shows selectivity for fluoride and phosphate.43, 44 The extremely limited body of work for O-H donor s in synthetic anion receptor systems, while surprising, offers the opportunity to make im portant contribution to th is field. Presumably, most receptors employ N-H donors opposed to O-H groups as they are relatively easy to organize. Creation of a binding cavity uti lizing O-H groups has proven synthetically challenging. In previous work with the pre-or ganization of phenols, our group has developed the triphenoxymethane molecule (Figure 1-10) and note d that it prefers an all up configuration, where all three phenols are pointed in the same direction with respect to the central methine carbon.45 This molecule is readily modified and its properties can easily be tuned. Research Objectives Our objective is to incorporat e the triphenoxymethane molecule into the backbone of a salen macrocycle for the use of selective ani on sensing. We envisione d creating a cavity of phenolic donors offering four OH groups available for anion coordination. This type of molecule would be the first example of a we ll defined receptor system that employs purely hydroxyl groups. As described above, the salen sy stem was chosen for its ability to provide a visual report, allowing the bi nding event to be monitored by UV-Vis spectroscopy. The choice of metal also plays an important role in structur ally regulating the cavity size. Herein, we report the design, synthesis and study of metal salen complexes and their anion binding properties.

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24 N N N N X X X X X X H3B BH3 BH3 H3B X=-(CH2)6Figure 1-1. Structure of Park and Simons katapinate ; the first example of an anion binder. Figure 1-2. Structure of azacryptand that is an id eal size match for fluoride and shows an extremely high binding constant for fluoride (logKs = 11.2) Figure 1-3. Structure of zwitte rionic neutral receptor. An ion coordination is done through electrostatic interactions only. N (CH2)nN (CH2)n(CH2)n H H X-n=7-10NHHN N HN N NH H N N H

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25 H N H N O O O O N HN NH2N NH HN HO OH Figure 1-4. Structure of the py rrolic macrocycle sapphyrin. U pon protonation there are five NHs donors that form hydrogen bonds to anions. Figure 1-5. Structure of two bicyclic gua nidiniums attached by a urethane linker. N H N H N H N N

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26 N HN NH N HN N NH N N N H N H O O O O O O N HN NH N HN N NH N O O O O Figure 1-6. Structure of neutral anion receptor. A B Figure 1-7. Structures of amide based receptors by Bowman-James N HN SO2R HN SO2R NH RO2S

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27 Figure 1-8. Structure of salen complex with uranyl used for Lewi s acidic anion binding Figure 1-9. Structure of conj ugated polymer that efficiently binds fluoride though phenols. Figure 1-10. Structure of triphe noxymethane platform with three phe nols aligned with respect to each other. R = t -bu HO OH HO R R H R "all up" N N O O O NHR2 R2HN O O O U O O NN O OH HO R2O OR2 R2 R1 R2O OR2 x1-x

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28 CHAPTER 2 METAL SALEN COMPLEXES INCORP ORATING TRIPHENOXYMETHANES: EFFICIENT, SIZE SELECTIVE BINDING OF FLUORIDE WITH A VISUAL REPORT Introduction For the design of anion receptors, Lewis acidic metals16 or organic ligands that employ hydrogen bonding and/or electrostati c interactions are often used.10 In the case of hydrogen bond donors, virtually all of the attention has focuse d on ligands incorporating N-H groups such as amides, amines, pyrroles, and ureas,22 and in some instances, meta ls help orient these groups.46 Surprisingly, despite the wide participation of serine and tyrosine hydr oxides in anion binding sites in biological systems in cluding ClC chloride channels47 and Bacteriorhodopsin48 among numerous others,49 the use of O-H donors in the design of anion receptors has been limited to only a handful of examples that are not particularly well defined systems.50 To provide hydrogen bond donors to coordinate anions, N-H as well as O-H donor groups can be used. A hydrogen bonding interaction ca n take place between a hydrogen covalently bound to an electronegative donor and an electronegative accepto r (D-HA). The limited work in the area of O-H based anion receptors may be due to the difficulties in pre-organizing O-H groups compared to N-H groups. The phenolic proton is quite acidic (pKa ~ 10) compared to that of amines (~26) and amides (~20) and thus O-H groups should form stronger hydrogen bonds than those formed by N-H groups. Results and Discussion The presence of O-H groups can increase th e affinity of N-H containing ligands for anions,51 but we envisioned that a tetrahedral pocket of phenolic donors templated by a metal could provide an ideal environmen t for the selective binding of anions, particularly since the size of the cavity could be modulated by the choice of metal. Metals also offer convenient pathways to report the binding event via spectra l changes. Salens have been engineered to orient two sets

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29 of N-H donors by several groups,52 and herein, we report the synthe sis and attributes of an anion receptor incorporating four phenols at the periphery of salen. Advantages of the Salen Macrocycle In previous work with triphenoxymethanes44 (Figure 2-2), a profound preference has been noted for the molecule to adopt an all-up or ientation wherein all thr ee phenolic oxygens align with respect to the central methine hydrogen. A derivative incorporating an aldehyde group on a single phenol can be readily isolated.53 The molecule reacts with 1,2-diamino cyclohexane to form 2-1 as outlined in Figure 2-3. A range of metals including Mn (II), Ni (II), Zn (II), and Pd (II) can be incorporated into the salen binding sites without affecting the f our remaining phenols. The six triphenoxymethane phenols still prefer to re main aligned, and since the metal coor dinates to two of them, a pocket is created which is lined by f our hydrogen bond donor groups in a ps eudo tetrahedral arrangement. Initial work on the development of an anion sensor has focused on the diamagnetic, square planar Ni (II) and Pd (II) metals since thei r radii differ by approximate ly ~0.15 providing the opportunity to adjust the size of the binding cavit y. Salen complexes with these metals also exhibit intense MLCT absorptions ( ~ 7400) in the visible region.54 The relative synthetic ease of the system and the possibility to tune the receptors properties by co mplexation of different metals offers many advantages and the synthe sis of the receptor is seen in Figure 2-3. Design of Receptor System Compound 2-1 has been structura lly characterized (Figure 2-4) and in the solid-state, the two sets of triphenoxymethanes align themselves on opposite sides of the 1,2diaminocyclohexane linker. The phenols remain aligned in the same di rection with respect to

PAGE 30

30 each other. The incorporation of a metal center in to the ligand aligns and rigidifies the molecule positioning the four remaining phenols into tetrahedral environment. For the development of an anion sensor, focus has been placed on the diamagnetic, square planar Ni (II) and Pd (II), providing the op portunity to adjust signi ficantly the size of the binding cavity. Ni (II) and Pd (II) are also d8 and prefer a square planer geometry which makes them diamagnetic and enables us to follo w the synthesis and anion binding by NMR spectroscopy. Salen complexes with these meta ls also exhibit intense MLCT absorptions ( ~ 7400) in the visible region54 and the compounds have shown significant color change upon addition of fluoride. Both Ni (II) (2-2) and Pd (II) (2-3) meta l complexes with 2-1 were structurally characterized, and in each, two symmetry independe nt molecules crystallized in the asymmetric unit. In both cases, the molecules were nearly indistinguishable, but the orientation of the unbound phenols with respect to the chiral centers on the cyclohexyl rings differed. The chiral R R -cyclohexyl backbone was used to isolate single cr ystals of 2-2 and the st ructure of one of the two symmetry independent molecules is presented in Figure 2-5. The chiral R R -1,2diaminocyclohexane backbone as well as the race mic version was used to isolate the Ni (II) complex. There were significant differences in so lubilities between the two molecules yet they showed identical UV-Vis and NMR spectra. While the racemic complex had a limited solubility the chiral receptor was soluble in solvents with a wide range of polarities. As expected, the average distance of th e four Ni-oxygen bonds in the two complexes (1.842(8) ) are typical for a Ni (II) salen complex55 but significantly shorter than the corresponding average Pd-oxygen dist ances (2.009(4) ). The subtle size difference between the two metals produces a profound in crease in the separation between the two sets of phenolic

PAGE 31

31 donors attached to the salen backbone. The di stance between the two methine carbons, C (15) and C (46), increases from 5.28 in 1-Ni (II) complex to 6.03 in the 1-Pd (II), and this increase manifests other changes. In both symm etry independent Ni (II) complexes, a phenolic group from each side of the cavity maintains sh ort hydrogen bonding interactions with the salen phenolates (O-O separations vary from 2.677( 7) to 2.885(9) ) and the two remaining phenolic oxygens are situated 2.762(7) or 2.784( 8) from each other, creating a cavity held together by several intramolecu lar hydrogen bonds. In contra st, only a single phenol hydrogen bonds to the salen phenolate in the cavity formed in 2-3 with a O-O separation of 2.824(4) and this oxygen also maintains a close cont act of 2.804(4) with a phenol oxygen on the opposite side of the cavity. The remaining two ph enols are more than 3.989 from the nearest oxygen. These intramolecular hydrogen bonding interact ions not only play a structural role, but may also have an effect on the colori metric properties of this system. Anion Binding Properties Anion binding properties of the two me tal complexes were tested with n -Bu4N+ halide salts in a variety of solvents including chlorofo rm, acetone, and DMSO, and both 2-2 and 2-3 complexes only reacted with fluorid e at low anion concentrations. The binding cavity appears to be too small to accommodate the larger anions and even after the addition of a large excess of Cl-, Br-, I-, NO3 -, ClO4 -, or HSO4 no changes could be detected in the 1H NMR or UV/Vis spectra. Treatment of 2-2 and 2-3 with one equiva lent of more basic anions such as H2PO4 and OAcproduced no discernable ch ange in the UV/Vis or 1H NMR spectrum other than the disappearance of the OH resonances in the 1H NMR spectrum, but at very high concentrations (> 30 eq), the anions induced precipitation in the NM R experiment and a small (<8 nm) shift of the absorption maxima in the UV/Vis spectra of the complexes.

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32 In contrast, the addition of fluoride to 2-2 induced a dramatic change in the 1H NMR spectrum, and with any amount less than a full eq uivalent of fluoride, the spectrum was quite broad, suggesting a rapid equili brium of fluoride between open binding sites since the complex remains diamagnetic. Unfortunately, cooling of th e sample initiated crystallization and variable temperature NMR experiments could not be perf ormed. Addition of fluoride to 2-3 produced a less dramatic effect on the 1H NMR spectrum of the complex (Figure 2-7), and the only significant change involved the two resonances a ssociated with the phenolic protons that shift from 6.83 and 6.44 ppm in d6-DMSO and appear as a doublet at 9.93 ppm ( JHF = 46 Hz). Similar magnitudes for H-F coupling constant s have been noted in halide receptors incorporating amides56 and pyrroles.57 The phenolic resonances for [2-2-F]1also occur as a doublet downfield at 9.69 ppm ( JHF = 42 Hz) in d6-DMSO, but in solvents such as CDCl3 and (CD3)2CO, the resonances for the phenolic proton s on both 2-2 and 2-3 are absent, presumably due to deuterium exchange with solvent. Fluor ide is known to facilitate deuterium exchange on amides in halide receptors.58 In the 19F NMR spectrum, a quintet resonance ( JHF = 46 Hz) slowly grows in at -117.2 ppm (referenced against trifluorotoluene at .7 ppm) as fluoride is added to a d6-DMSO solution of 2-3, intimating that the four phenolic O-HF interac tions are equivalent and produce the 2 nI + 1 quintet resonance. After addition of more than a one equivalent of anion, a new resonance arises at -145.7 ppm, the normal position of the resonance of free fluoride ion. The 19F NMR spectrum of 2-2 after addition of fluoride exhibi ted a broad resonance at -116.2 ppm, and the value for the H-F coupling constant could not be accurately determin ed. Once again, solvents such as chloroform and acetone favor deuterium excha nge, and all H-F coupling in the 19F NMR disappear in these solvents.

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33 Addition of fluoride to 2-2 and 2-3 disrupts the hydrogen bonds to the salen phenolates and induces a red shift in the ML CT absorption with two distinct isobestic points (Figure 2-11), intimating a single species forms in solution. In the case of 2-2, the absorption shifts from 411 nm to 431 nm with a small decrea se in the molar absorptivity wh ile the 2-3 exhibits a slightly larger shift from 407 nm to 440 nm. The color ch ange is abrupt and can easily be seen by the naked eye. The determination of the binding mode of the anion and the ratio of bound anion to receptor requires the production of Job plots. Both 1HNMR and UV-Vis spectral data are commonly used to derive Job plots, bu t due to the complicated nature of 1H NMR spectrum and the clarity of the absorption data for 2-2, UV-Vis spectra were used to determine the guest-host stoichiometry. The location of th e apex of the plot indicates the ratio of fluoride bound to each 2-2 molecule. A Job plot for the spectral da ta of 2-2 shows a maximum at 0.5 indicating a single equivalent of fluori de binds in the phenolic cavity (Figure 2-12). Binding Constants The binding constants (Ks) were determined from the da ta obtained by UV-Vis spectroscopy fluoride titrations. The measured absorbance were plotted as a f unction of fluoride ion concentration of the solution at 450nm and a non-linear least squares regression was used to determine binding constants with the equation:59 X = X0 + [(Xlim X0) / 2c0] [c0 + cm +1/Ks [(c0 + cm + 1/Ks)2 4c0cm]1/2]. In this equation, X is the measured absorbance, X0 is the initial absorbance, Xlim is the limiting absorbance, c0 is concentration of anion in solution, cm is the concentration of the receptor, and Ks is the binding constant. A program to perform a non-linear least squares regression on the data60 which minimizes the error of each data point to fit the standard equation by altering Ks was written in excel. The value of Ks that leads to the lowest sum of errors is the binding constant for the system. The logKs values (errors %) were

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34 determined to be 5.6 for 2-2 and 5.8 for 2-3 in acetone (logKs = 5.8 for both complexes in DMSO). Solid State Structure of [2-2-F]1Single crystals of the 2-2 with a fluoride ion were obtained, and in the solid state (Figure 214), the fluoride is held in the phenolic cavity by three short and one long hydrogen bond to form [2-2-F]1(fluorine oxygen separations of 2.539(2) 2.509(2) 2.573(2) and 3.098(3) ). Although the resonances ar e a bit broader than the data pr esented in Figure 3 for [2-3-F]1-, the solution NMR spectra for [2-2-F]1suggest the fluoride is held in a symmetric environment by the four phenols, and the lone, long OHF interactio n may be an artifact of crystal packing. In order to fit the anion, the phenolic poc ket has had to open up, and the separation between the methine carbons, C(15) and C(46), has increased by almost 0.5 to 5.73 in comparison to 2-2. Ni (II) appears to be resisting the increase in si ze of the cavity, and the metal distorts from planarity with an angle of 15.8 between the two NNi-O planes in the salen. The cavity created by the Pd(II) center should be able to accommodate the fluoride anion with much less distortion, since the separation between C(15) and C(46) is already 6.03 in 2-3 which may lead to the larger Ks (logKs = 5.81) compared to that of 2-2. The clarity of the 1H NMR spectrum of 2-3 during the titration expe riment suggests structural distor tions are less pronounced than in 2-2. Anion Binding Studies for 2-3 Binding studies of compound 2-3 were tested wi th the various anions and the increase in cavity size for 2-3 between the methine carbons to 6.03 compared to 5.23 in the Ni complex was quite dramatic and the ability to bind larger an ions was a possibility. As with 2-2, 2-3 had a profound affinity for fluoride while showing no interaction with othe r anions. Titration experiments with tetrabutylammonium salts in acetone, and once again showed there was no

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35 change in the NMR spectra or UV-Vis spectra from Cl-, Br-, I-, NO3 -, ClO4 -, or PO4 3-. Titration of 2-3 with fluoride led to a large red shift in the absorbance spectra, where the main absorption shifts from 407 nm to 440 nm. There were also two isobestic points for this titration implying only a single product is formed. The job plot for 2-3 shows that fluoride binds to the Pd complex in a 1:1 ratio (Figure 2-16). Even though the cavity of 2-3 is considerably larger than 2-2 it is still size selective for fluoride and can not accommodate other large anions. The io nic radius of fluoride is considerably smaller than that of most other anions at 1.36, such as chloride (1.81), and phosphate (2.38). The larger cavity does have an effect on th e binding ability of fluoride and influences several of the proper ties of 2-3. The 1H NMR spectrum of 2-2 with le ss than one equivalent of fluoride is very complicated possibly due to a fast exchange of fluoride between open binding sites. However, compound 2-3 has only mi nor changes in the spectrum other than the disappearance of the peaks representing the two di fferent phenols in the structure. Due to the increased cavity size there is potentially a l ack of strain places on 2-3 upon binding fluoride eliminating the exchange that is seen with 2-2. Another cons equence is the slightly higher binding constant of 2-3 which has a logKs of 5.81 compared to 2-2 which has a logKs of 5.64. Conclusions In conclusion, a salen ligand, 2-1, has been designed with a pair of phenolic donors tethered to the ortho -position of each of the salen phenols. Complexation of square planar metal centers into the macrocyclic binding pocket forces the four remaining phenolic groups to form a tetrahedral array, and this pocket tightly binds fluoride. The ion is bound by three short and one long O-HF interactions, representing a rare example of efficient anion binding by purely OH hydrogen bonding in a well-defined sensor The bi nding event induces a redshift in the intense

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36 MLCT transition, offering a distin ct visual report of the binding ev ent. Efforts to increase the size and the number of phenolic donors that create the cavity by us ing different metal centers and amine linkers are currently underway. Experimental Methods General Considerations 1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at 299.95 and 75.47 MHz for the proton and carbon cha nnels. UV-Vis spectra were recorded on a Varian Cary 50 spectrometer. Elemental analyses were performed at either the in-house facility of the Department of Chemistry at the Univ ersity of Florida or by Complete Analysis Laboratories Inc., Parsippany, NJ. All solven ts were ACS or HPLC grade and used as purchased. For the metalation reactions, the solvents were dried with a Meyer Solvent Purification system. Synthesis of 2-1 A portion of 0.63 g (5.52mmol) of 1,2-diami nocyclohexane was dissolved in 50 mL absolute ethanol. To this solution a slurry of 5.00 g (11.05 mmol) of 3-(2,2-Methylenebis (4methyl-6tertbutylphenol)-5-methyl-2-hydroxybenzaldehyde53 in 300 mL ethanol was added. The reaction was refluxed open to the air for 12 hours. The solution was cooled to room temperature and water was added to the solution re sulting in the precipita tion of a bright yellow solid. The solid was filtered and dried to afford the product in 83% yield (4.73 g). 1H NMR: 8.12 (s, 2H); 7.04 (s, 4H); 6.93 (s, 2H); 6.77 (s, 2H ); 6.66 (s, 4H); 5.94 (s, 2H); 5.62 (s, 2H); 5.40 (s, 2H); 3.30 (d, 2H); 2.20 (s, 6H); 2.17 (s, 6H); 2 .10 (s, 6H); 2.00-1.85 (m,); 1.38 (s, 36H). 13C NMR 165.4; 157.7; 151.4; 137.7; 134.5; 131.2; 129.2; 128.3; 127.9; 127.7; 127.5; 117.9; 72.0; 39.2; 34.9; 33.2; 30.0; 24.33; 21.3; 20.7. HR-FABMS: calcd for C68H87O6N2 1027.6564; found 1027.6568 [MH+]. IR: [cm-1] 3495 (OH); 1625 (C=N).

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37 Synthesis of R R -2-1 Using a modified literature procedure,61 a portion of 2.00 g (7.57 mmol) of ( R R )-(-)-1,2diaminocyclohexane mono-L-(+)-tartrate was mixed with 2.09 g (15.14 mmol) of potassium carbonate and dissolved in 15 mL wa ter. To this solution, 60 mL of absolute ethanol was added and the solution was brought to a reflux. A slurry of 6.85 g (15.14 mmol) 3-(2,2-Methylenebis (4-methyl-6tertbutylphenol)-5-methyl-2-hydroxy-benzal dehyde in approximately 150 mL of ethanol was slowly added to the amine with an addition funnel. The solution was then refluxed for three hours. 20 mL of water was added and it was cooled in the refrigerator for 12 hours. The bright yellow solid was filtered and then di ssolved in methylene chloride. It was washed three times with water in a sepa ratory funnel, dried with magnesi um sulfate and the solvent was removed to afford the pure pr oduct in 78% yield (6.05 g). 1H NMR: 8.12 (s, 2H); 7.04 (s, 4H); 6.93 (s, 2H); 6.77 (s, 2H); 6.66 (s, 4H); 5.94 (s, 2H ); 5.62 (s, 2H); 5.40 (s, 2H); 3.30 (d, 2H); 2.20 (s, 6H); 2.17 (s, 6H); 2.10 (s, 6H ); 2.00-1.85 (m,); 1.38 (s, 36H). 13C NMR 165.4; 157.7; 151.4; 137.7; 134.5; 131.2; 129.2; 128.3; 127.9; 127.7; 127.5; 117.9; 72.0; 39.2; 34.9; 33.2; 30.0; 24.33; 21.3; 20.7. Synthesis of R R -2-2 A portion of 1.0 g (0.974 mmol) R R -1-H2 was dissolved in dry THF. To this solution 0.27 g (10.30 mmol) of nickel acetate was added a nd it was refluxed under nitrogen for 12 hours. The solution was cooled, filtered and the solvent removed. The remaining solid was then dissolved in pentane, filtered and a dark red solid was obtained in an 87% yield (0.92 g). Crystals suitable for X-ray diffraction were gr own by slow evaporation from a concentrated acetonitrile solution. 1H NMR: 7.45 (s, 2H); 7.17 (d, 2H); 6.87 (s, 4H); 6.83 (s, 2H); 6.76 (s, 4H); 6.57 (s, 2H); 6.38 (s, 2H); 6.25 (s, 2H); 3.20-3.15 (m, 2H); 2.55-2.45 (m, 2H); 2.17 (s, 6H); 2.14 (s, 12H); 2.00-1.9 (m, 2H); 1.12 (s, 18H); 1.11 (s, 18H). 13C NMR 158.2; 152.0; 151.8;

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38 137.5; 137.3; 137.2; 132.2; 130.6; 128.9; 128.6; 127.4; 127.3; 126.6; 126.8; 119.6; 70.3; 36.4; 34.6; 29.5; 28.7; 24.4; 21.0; 20.4. Anal. Calc. for C68H84N2O6Ni CH3CN: C, 74.72; H, 7.79; N, 3.73. Found C, 74.24; H, 7.84; N, 3.44. Synthesis of 2-2 A portion of 1.0 g ( 0.974 mmol) of 1-H2 was dissolved in dry THF. To this solution 0.27 g (1.07 mmol) of nickel acetate was added and it was refluxed under nitrogen for 12 hours. The solution was cooled, filtered and the solvent removed. The solid was then washed with pentane and filtered producing a red solid product in 91% yield (0.96 g). 1H NMR: 7.45 (s, 2H); 7.17 (d, 2H); 6.87 (s, 4H); 6.83 (s 2H); 6.76 (s, 4H); 6.57 (s, 2H); 6.38 (s, 2H); 6.25 (s, 2H); 3.203.15 (m, 2H); 2.55-2.45 (m, 2H); 2.17 (s, 6H); 2.14 (s, 12H); 2.00-1.9 (m, 2H); 1.12 (s, 18H); 1.11 (s, 18H). 13C NMR 158.2; 152.0; 151.8; 137.5; 137.3; 137.2; 132.2; 130.6; 128.9; 128.6; 127.4; 127.3; 126.6; 126.8; 119.6; 70.3; 36.4; 34.6; 29.5; 28.7; 24.4; 21.0; 20.4. Synthesis of 2-3 Using a modified literature procedure,62 a portion of 1.00 g (0.974 mmol) of 1-H2 was dissolved in dry ether. To this solution 0.092 g (2.14 mmol) sodi um methoxide was added along with 0.240 g (1.07 mmol) of palladium acetate. Th e solution was refluxed for three hours under nitrogen during which time a gr een precipitate formed. The solution was cooled and the precipitate was filtered. The product was rediss olved in methylene chloride, filtered and then solvent was removed leaving a yellow solid in a 62% yield (0.68 g). Crysta ls suitable for X-ray diffraction were grown by a chlo roform / pentane diffusion. 1H NMR: 7.57 (s, 2H); 7.10 (d, 2H); 6.98 (s, 4H); 6.95 (s, 2H); 6.91 (s, 2H); 6.88 (s 2H); 6.60 (s, 2H); 6.58 (s, 2H); 6.28 (s, 2H); 5.81 (s, 2H); 3.50-3.40 (m, 2H); 2.4 1 (d, 2H); 2.16 (s, 6H); 2.14 (s 6H); 2.09 (s, 6H); 1.71 (d, 2H); 1.28 (s, 18H); 1.18 (s, 18H). 13C NMR 160.49; 156.44; 151.26; 138.74; 137.58; 136.90; 134.04; 132.91; 130.16; 129.61; 128.60; 128.41; 128.06; 125.91; 125.08; 120.64;

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39 72.62; 38.86; 34.89; 30.05; 28.99; 24.47; 21.47; 20.23. Anal. Calc. for C68H84N2O6Pd: C, 72.16; H, 7.48; N, 2.48. Found C, 72.03; H, 7.65; N, 2.51. Synthesis of [2-2-F](Bu4N) A portion of 0.050 g (0.046 mmol) of 1-Ni along with 0.029 g (0.092 mmol) tetrabutylammonium fluoride trihydrate was dissolved in 1 mL toluene. Crystals suitable for X-ray diffraction were grown by a slow diffusi on of pentane into toluene solution. 1H NMR: 7.44 (s, 2H); 7.16 (d, 2H); 6.86 (s, 4H); 6.83 (s, 2H); 6.7 5 (s, 4H); 6.37 (s, 2H); 3.37 (m, 8H); 3.14 (s, 2H); 2.46 (m, 2H); 2.17 (m, 6H); 2.13 (s, 12H); 1.92 (m, 2H); 1.68 (m, 8H); 1.46 (q, 8H); 1.30 (m, 2H); 1.12 (s, 18H); 1.10 (s, 18H); 1.02 (t, 12H). Anal. Calc. for C84H120N3O6NiF: C, 74.98; H, 8.99; N, 3.12. Found C, 74.24; H, 8.91; N, 2.64. Determination of binding constants (LogKs) A 4.61 x 10-5M solution of 2-2 in acetone was titrated with 23 L aliquots of a tetrabutylammonium fluoride solution. Absorbance was plotted versus fluoride concentration at 450 nm and a non-linear least squares regression wa s then run on the data using the following equation:59 X = X0 + [(Xlim X0) / 2c0] [c0 + cm +1/Ks [(c0 + cM + 1/Ks)2 4c0cM]1/2]. By solving this equation for Ks we were able to obtain logKs of 5.64 for 1-Ni(II) and 5.81 for 2-3.

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40 ClO H Y445 HO S107 N H I356 N H O F357 O Table 2-1. X-ray data for the crystal structures of 2-1 and the complexes R R -2-1, 2-3, and 2-2-F. 2-1CH3CN R R -2-2CH3CN 2-3Et2O 2-2-FEt2O total reflections unique reflections max empirical formula Mr crystal system space group a () b () c () ( ) ( ) ( ) Vc (3) Dc (g cm-3) Z (MoK ) (mm-1) R1 [ I 2 ( I ) data]b w R2 (all data)c GoF 16607 10576 25 C70 H89 N3 O6 1068.44 triclinic P-1 13.8245(12) 14.1393(12) 17.9268(15) 70.554(2) 89.380(2) 71.177(2) 3109.2(5) 1.141 2 0.072 0.0907 0.1629 0.946 18198 14424 28 C72 H90 N4 O6 Ni 1166.19 triclinic P1 13.1800(9) 13.7606(10) 20.2871(14) 83.2670(10) 77.1700(10) 66.1000(10) 3278.4(4) 1.181 2 0.349 0.0506 0.1179 1.019 40023 26428 28 C70H89 N2 O7 Pd 1176.86 triclinic P-1 16.6011(11) 21.7001(15) 23.4994(16) 71.3800(10) 86.2890(10) 71.1520(10) 7585.3(9) 1.031 4 0.289 0.0584 0.1230 0.821 29805 19898 28 C88 H130 F N3 O7 Ni 1419.66 triclinic P-1 13.7248(9) 17.0299(11) 22.1543(14) 71.4080(10) 89.0850(10) 72.8510(10) 4672.3(5) 1.009 2 0.257 0.0608 0.1687 0.968 Figure 2-1. Schematic diagram of the open conforma tion of ClC chloride ch annel. Chloride is held in place by two OH-Cl hydrogen bonds from Y445 and S107.

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41 Figure 2-2. Triphenoxymethane platform with the phenols in the all up pos ition relative to the methine carbon hydrogen. Figure 2-3. Procedure used for the synthesis of 2-1, macrocycle metalation to form 2-2, and 2-3 and fluoride binding. R = t -bu HO OH HO R R H R "all up"HO H2NNH22eq M(OAc)2 Bu4NF M OH HO NN H O O HO OH M OH NN O O OH FHO H H H M=Ni,Pd R= t -bu Romittedforclarity HO OH HO R R H O H + "allup" N N HO H R OH OH HO R HO R OH R H 2-2,2-3 [M(II)-F]-Ligand2-1

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42 Figure 2-4. Depiction of the solid-state structur e of 2-1 (30% probability ellipsoids for nitrogen and oxygen, carbons drawn w ith arbitrary radii)

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43 Figure 2-5. Depiction of the solid-state structur e of 2-2 (30% probability ellipsoids for nitrogen, oxygen and nickel, carbons draw n with arbitrary radii)

PAGE 44

44 Figure 2-6. Depiction of the solid-state structures of 2-3 (30% probability ellipsoids for nitrogen, oxygen and palladium, carbons drawn with arbitrary radii)

PAGE 45

45 Figure 2-7. 1H NMR spectrum of 2-3 (top) and [2-3-F]1(bottom) taken in d6-DMSO with an inset of the 19F NMR spectrum of [2-3-F]1in the region of bound fluoride. Figure 2-8. 1H NMR spectrum of 2-2 with a sharp and well defined aromatic region.

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46 Figure 2-9. 1H NMR spectrum of 2-2 with 0.5 e quivalents of fluoride added. Figure 2-10. 1H NMR spectrum of 2-2 with one e quivalent or more of fluoride.

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47 Figure 2-11. UV-Vis titration of 2-2 (4.61x10-5 M) with tetra-butyl ammonium fluoride in acetone. Titration was complete after the addi tion of a single equiva lent of fluoride. Inset shows the change in color upon ani on coordination from br ight red to dark green. Figure 2-12. Job plot shows the titration of 2-2 with tetrabutylammonium fluoride. Apex at 0.5 indicates a 1:1 binding mode of anion to re ceptor. [L] = concentration of receptor; [A] = concentration of anion; A = absorbance.

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48 Figure 2-13. Absorbance plotted versus concentr ation of fluoride for th e titration of 2-2 at 450nm with tetrabutylammonium fluoride. The data points represent experimental values and solid line represents the fit to the data.

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49 Figure 2-14 Crystal structure of [2-2-F]1with fluoride bound in the phenolic pocket. The tetrabutylammonium cation, solvates, and hydrogens have been omitted for clarity. Selected distances: (a) C(15)C(46) 5.28 ; O(1)O(3) 2.697(7) ; O(4)O(5) 2.784(8) (b) C(15)C(46) 5.73; O(2)F (1) 2.539(2) ; O(3)F(1) 2.509(2) ; O(5)F(1) 3.098(3) ; O( 6)F(1) 2.573(2)

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50 Figure 2-15. UV-Vis titration of 2-3 salen (4.61x10-5 M) with tetra-butylammonium fluoride in acetone. Titration was complete after the addi tion of a single equi valent of fluoride. Figure 2-16. Job plot from UV-Vis spectra ti tration data of 2-3 in acetone with tetrabutyammonium fluoride

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51 Figure 2-17. Absorbance plotted versus concentra tion of fluoride for the t itration of 2-3 complex at 450 nm with tetrabutylammonium fluoride. The data points re present experimental values and solid line represents the calculated values.

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52 CHAPTER 3 A SYNTHETIC MODEL OF TH E CLC CHLORIDE ION CHA NNEL; A STRUCTURAL AND ANION BINDING STUDY Introduction In nature, the ClC chloride channel selectivel y transfers chloride ions across membranes, and with the recent elucidation of the structure by MacKinnon and coworkers, a clear picture of the halide binding site is now available.47 At one point in the transfer process, chloride is held by hydrogen bonds to four amino acid residues. Amide nitrogrens from Ile 356 and Phe 357 provide two hydrogen bonds while the hydroxide groups on Ser 107 and Tyr 445 provide the remaining stabilizing interactions. In this in stance, nature employs a mixture of N-H and O-H donors for the transportation of halides, but surpri singly, the scie ntific community has primarily focused their efforts on the use of N-H groups such as amides, amines, pyrroles, and ureas to provide the hydrogen bonding interactions for artificial anion receptors.22 The utility of O-H groups in anion receptors has been quite limited w ith only a handful of examples reported in the literature.50 Recently, we demonstrated that four phenol s could be carefully positioned to produce a selective and efficient recep tor for the fluoride anion.63 In this system, the phenolic groups were tethered to a salen macrocycle, and metal comple xation helps to orient the four groups into a pocket via hydrogen bonding and ster ic interactions. The metal macrocycle receptor offered other advantages such as the capacity to modul ate the size of the halid e binding pocket and the ability to monitor the binding event through spec tral changes in the intense MLCT transitions. In view of the proclivity for 2-1 to bind selectively fluoride and the mixed N-H and O-H binding site found in the ClC channel, we set out to prepare a structural model of the ClC channel with a mixture of two N-H and two O-H donors attached to the sa len backbone. Herein,

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53 we report the synthesis and study of a ClC channe l model complex with a focus on its structural and anion binding properties. Results and Discussion For the design of artificial ani on receptors, the salen macrocyc le offers many advantages. The ligands are easily prepared via a simple Schiff base condensation of salicylaldehyde and a diamine, and a range of donor groups adept at bi nding to both cationic and anionic groups can be attached to the salicylaldehyde mo iety with little synthetic effort Incorporation of a metal center into the macrocyclic rings affords a rigid framew ork, and if the donor groups are properly placed in the periphery of the salicyl aldehyde, a tight binding pocket can be produced at the cleft between the two sides of the macrocycle. The size of the binding site can be modulated by changing the identity and radii of the metal cente r within the macrocycle, and since metal salen compounds normally exhibit MLCT transitions in the visible region, the binding event can often be followed by monitoring the position of this intense absorption band. Salens as Anion Receptors Reinhoudt and coworkers were the first to utilize metal salens for anion binding.39 Their strategy focused on using acetoamido groups tethered to the salen phenoxide groups to act as hydrogen bond donors to a phosphate anion, while ura nyl was incorporated into the macrocycle to provide hydrogen bonding acceptor site for th e phosphate proton. Salens can also act as receptors for Ni(II) and Cu(II) sulfate when am ine groups are bound at the periphery of the macrocycle.52 We have recently demonstrated that four phe nols tethered to a sale n backbone in a pseudo tetrahedral arrangement creates an efficient and se lective fluoride sensor. Initial work with 2-1 focused on the diamagnetic and square planar metals Ni(II) and Pd(II) which afforded the opportunity to monitor the receptor synthesis and the anion binding event by NMR spectroscopy.

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54 Each molecule was structurally characterized an d the difference in metal radii had an impact on the size of the binding cavity as well as an influence of the binding constants for fluoride. Binding properties of these complexes were tested with n -Bu4N+ halide salts in a variety of solvents. The intense MLCT absorptions ( ~ 7400) offered by both 2-2 and 2-3 offer a convenient way to monitor the fluoride binding even t. Addition of fluoride to these receptors causes a dramatic red shift in the absorption spectrum with two distinct isobestic points indicating a single species fo rms in solution. The logKs values were determined to be 5.6 for 2-2 and 5.8 for 2-3 in acetone and were 5.8 for bot h complexes in DMSO. Both 2-2 and 2-3 only reacted with fluoride. Steric constraints in the binding cavity precluded the binding ability of larger halides Cl-, Br-, and I-. Upon addition of large excesses of the larger anions no changes were detected in the 1H NMR spectrum or the UV-Vis spectra. Synthesis of a Mixed Salen Receptor With the ability to incorporate O-H donors into an anion receptor system, we envisioned a synthetic mimic of the ClC chloride channel co uld be created, but this would also require two amide type N-Hs to replicate the donors from Ser 107 and Tyr 445. The salen macrocycle can be used as a way to organize groups for anion binding, and mixed salen systems that involve two different moieties have been reported in hi gh yields. However, to employ this method a molecule with N-H donor groups that could be in corporated into a salen system had to be developed.64 In our group, Melanie Veige isolated a urea s ubstituted salicylalde hyde and this group can be incorporated into a salen macrocycle (Figur e 3-4). The resulting m acrocycle would provide two N-H donors from the urea group.65 Urea groups are a common motif in synthetic anion receptor systems and have shown the ability to coor dinate a range of anions including the target chloride ion.66 The two N-H groups from the urea are separated by a carbonyl creating an

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55 environment that is similar to the backbone of th e protein. Both N-Hs are also aligned in the same direction which is critical to the receptor for anion coordination. While mixed salen systems have previously be en reported, they have included only simple salicylaldehydes,64 so the incorporation of highly functi onalized groups would require modified procedures to obtain the desired mixed salen products. With a combination of urea and the two phenolic groups onto a single platform, the molecu le could serve as a model of the ClC channel with two O-H and two N-H donors available for an ion coordination. In order to synthesize a mixed salen product, 1,2-diaminocyclohexane HCl was prepared and the hydrochloride salt acts as a protecting group to prevent fu rther reactions at one of the amine positions. A stepwise series of condensation reactions followed by metalation with Ni(II) (Figure 3-5) affords a product. The choice of solvent, reaction time, temperat ure and purification methods are critically important to the synthesis of this system. The isolation of (3-6) is readily attainable, but the condensation of 3-6 and the urea compound 3-5 often leads to a mi xture of products. The major product formed is 2-1 as the imine bond of 3-6 breaks and a rearrangement of the molecule is occurring. Rather than forming a compound w ith both the phenol group and urea groups, the major products of the reaction were the bis-pheno l and bis-urea compounds. Initial attempts for the formation of 3-7 were performed in ethanol as most salens, includ ing mixed salen systems,64 are typically carried out in this solvent. However, the isolatio n of the desired product was never obtained in polar solvents. Co mpound 3-7 was synthesized by a reaction in methylene chloride at room temperature. The isolation of the pure product was never obtained, as column chromatography of salen molecules can lead to decomposition due to the high sensitivity of the imine bonds. Metal salen compounds are usually more stable than the uncoordinated ligand, and

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56 upon the metalation of 3-7 with Ni (II) a more rigid compound (3-8) was easily purified with an overall yield of 20%. Anion Coordination and Binding Constants The anion binding properties of this system were tested by the addition of tetrabutylammonium halide salts to solutions of the recepto r. Compound 3-8 was able to bind fluoride and chloride while having no interact ion with the larger bromide ani on. A distinct red shift in the strong MLCT absorptions is detected upon ani on complexation for both fluoride and chloride with the main absorption peaks of the spectrum shifting from 411 nm to 428 nm for fluoride and from 411 nm to 421 nm for chloride. The addition of a large excess of bromide to the solution causes no changes to either the UV-Vis or NMR spectra. The binding constants (Ks) were determined from the data obtained by UV-Vis spectroscopy anion titrations. The measured ab sorbance were plotted as a function of fluoride ion concentration of the soluti on at 450nm and a non-lin ear least squares regression was used to determine binding constants with the equation:59 X = X0 + [(Xlim X0) / 2c0] [c0 + cm +1/Ks [(c0 + cm + 1/Ks)2 4c0cm]1/2]. In this equation, X is the measured absorbance, X0 is the initial absorbance, Xlim is the limiting absorbance, c0 is concentration of anion in solution, cm is the concentration of the receptor, and Ks is the binding constant. A program to perform a non-linear least squares regression on the data60 which minimizes the error of each data point to fit the standard equation by altering Ks was written in excel. The value of Ks that leads to the lowest sum of errors is the binding constant for the sy stem. Binding constants for 3-8 were determined to be Log Ks = 8.3 for fluoride and Log Ks = 1.74 for chloride. The coordination of fluoride occurs readily as seen by its extremely high bi nding constant. Although ch loride does coordinate to the receptor, it is less favorable. The larger si ze of chloride as well as its lower charge density

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57 led to the smaller interactions. Compound 3-8 fully coordinates fluoride upon addition of ~ 1 equivalent of anion while it take s ~ 30 equivalents of chloride to fully titrate the receptor. Solid State Structure Upon addition of excess chloride ion, 3-8 bi nds the anion and single crystals of the complex with chloride coordinated were obtained. In the solid state (Figure 3-7), chloride is held in the cavity by four rather strong hydrogen bonds (chloride o xygen distances of 3.158(3) and 3.108(4); chloride nitrogen distan ces of 3.512(4) and 3.183(4)). Th ere is a slight distortion of the urea group and the phenols in order for the receptor to accommodate the chloride ion. These small structural changes to the receptor, which are caused by anion coordination, have also been observed for 2-1 upon binding fluoride. Conclusions A synthetic model of a ClC chloride channe l has been designed and developed. The incorporation of phenolic and ur ea subunits onto a salen macroc ycle platform has created a highly functionalized mixed salen system which is able to coordinate chloride in a similar manner as seen in receptors found in nature. A so lid-state structure of 38 with a chloride anion bound has been obtained and it shows the binding mode with chloride interacting with all four hydrogen bond donors in the system. The structure is the first exam ple of a synthetic chloride receptor that involves the same hydrogen bonding inte ractions as the ClC chloride ion channel. The positioning of the donor group to form a cavit y of a specific size are important to the anion binding event as the receptor can easily accomm odate fluoride and chloride while there are no interactions with larger anions such as bromide. Binding constants for the receptor system have been obtained and follow the expected selectivity trend with a great er preference for the smaller anions. The metalated salen macrocycle serves multiple purposes, as a rigidify ing structural component and also it enables

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58 the binding constants to be m onitored by UV-Vis spectroscopy due to strong MLCT transitions. The receptor has a high binding constant for fluoride of log Ks = 8.3 and a much lower log Ks = 1.74 for chloride. There is no evidence that the la rger bromide anion intera cts with the receptor. Experimental Methods General Considerations. 1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at 299.95 and 75.47 MHz for the proton and carbon cha nnels. UV-Vis spectra were recorded on a Varian Cary 50 spectrometer. Elemental analyses were performed at either the in-house facility of the Department of Chemistry and the University of Florida. All solvents were ACS or HPLC grade and used as purchased except for metalation reactions where the solvents were dried with a Meyer distillation system prior to use. Mela nie Veige was responsible for the synthesis of compounds 3-1 through 3-5. Determination of binding constants (LogKs) A solution of receptor in acetone was titrated with aliquots of a tetra-butylammonium halide solution. Absorbance was plotted versus fluoride concentrati on at 450 nm and a nonlinear least squares regression was then r un on the data using the following equation:59 X = X0 + [(Xlim X0) / 2c0] [c0 + cm +1/Ks [(c0 + cM + 1/Ks)2 4c0cM]1/2]. Solving this equation for Ks gives the binding costant. Job plots we obtaine d by measuring the absorbance of a series of solutions with different proportion of recep tor and anion and indicate a 1:1 ratio. Synthesis of 3-1 A solution of 5-tert-butyl-2-hydroxybenzalde hyde (60.0 g, 337 mmol) in glacial acetic acid (240 mL) was cooled in an i ce bath. Fuming nitric acid (15.3 mL, 1 equiv., 337 mmol) was slowly added via addition funnel. After 15 min of stirring, the ice bath was removed and the solution was stirred at ambient temperature for 90 min. The ice bath was reapplied intermittently

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59 to prevent the internal reaction temperature fr om exceeding ca. 45 C. The reaction mixture was poured onto crushed ice (800 mL). The yellow preci pitate thus formed was filtered and washed with water, then recrystallized from abs. EtOH/H2O to give 3-1 as a yellow crystalline solid (68.7 g, 91%). The compound was used without fu rther purification. An analytically pure sample was obtained by further purification by co lumn chromatography (pentane-ether 3:1). 1H NMR (DMSOd6): 11.34 (bs s, OH), 10.28 (s, CHO), 8.20 (d, J =2.4 Hz, Ar-H), 8.07 (d, J =2.4 Hz, Ar-H), 1.30 (s, 9H). 13C NMR (DMSOd6): 191.5, 151.8, 142.3, 137.6, 132.6, 127.7, 124.9, 34.2, 30.6. HRMS (EI): Theoretical 223.0845; Measured 223.0837. Anal. Calc. for C11H13NO4; C, 59.46; H, 5.97; N, 6.22. Found C, 59.19; H, 5.87; N, 6.27. Synthesis of 3-2 To a solution of 3-1 (53.3 g, 239 mmol) in CHCl3 (350 mL) was added 1,3-propanedithiol (24 mL, 1 equiv.). The mixture was stirred at am bient temperature for 60 min. then was cooled in an ice bath. To the cold mixture was added BF3OEt2 (3 mL, 0.1 equiv., 23.9 mmol). The mixture was stirred 16 h with gradual warming to ambient temperature. The reaction mixture was transferred to a separato ry funnel, diluted with CHCl3 (250 mL), and washed successively with H2O (3x100 mL) and brine (150 mL). The volatiles were removed in vacuo and EtOH (250 mL) was added to the residue. The slurry was sti rred at ambient temperature for 1 h, then cooled in an ice bath for 30 min. The mixture was filter ed and the collected solids were washed with cold EtOH. 3-2 was obtained as a bright yellow crystalline solid (65 g, 87 %). An analytically pure sample was obtained via further purifica tion by column chromatography (pentane-ether 4:1). 1H NMR (DMSOd6): 10.64 (br s, OH), 7.86 (d, J =2.4 Hz, Ar-H), 7.79 (d, J =2.4 Hz, ArH), 5.73 (s, dithiane-H), 3.19-3.11 (m, 2H), 2.94-2.29 (m, 2H), 2.21-2.15 (m, 1H), 1.82-1.69 (m, 1H), 1.27 (s, 9H). 13C NMR (DMSOd6): 146.8, 142.3, 135.7, 132.3, 130.0, 120.9, 42.3, 34.0,

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60 31.2, 30.7, 24.6. HRMS (EI): Theoretical 313.08 06, measured 313.0820. Anal. Calc. for C14H19NO3S2: C, 53.99; H, 6.24; N, 4.42. Found C, 53.65; H, 6.11; N, 4.47. Synthesis 3-3 To a mixture of 3-2 (46.7 g, 149 mmol) in EtOH (475 mL) and AcOH (475 mL) was added Fe powder (33.3 g, 4 equiv., 597 mmol). The mixt ure was heated to reflux under a nitrogen atmosphere. The mixture gradually became a ve ry dark solution, and after approximately 1 h copious solids precipitated. After 1 h at reflux TLC indicated completion of the reaction. The mixture was concentrated in vacuo and EtOAc (300 mL) and H2O (300 mL) were added. Saturated K2CO3 was added to neutralize the aqueous la yer. The aqueous layer was extracted with additional EtOAc (3x65 mL). The combined organic fractions were washed with brine, dried over MgSO4 and filtered. The solution was transferred into a round-bottomed flask equipped with a stir bar. HCl in dioxane (4N, 75 mL, 300 mmol, 2 equiv.) was added slowly via addition funnel. The mixture was stirred at ambien t temperature for 3 h, then transferred to a -20 C freezer for 16 h. The mixture was filtered col d, and the collected solids washed with cold EtOAc to provide the HCl salt of 3-3 as a beige powder. The mother liquors were concentrated to approximately 200 mL and cooled to obtain a s econd crop of product. A total of 43.1 g (90%) of the HCl salt of 3-3 was obtained. Salt 33 (22.6 g, 70.8 mmol) was charged into a roundbottomed flask with CH2Cl2 (150 mL) and H2O (150 mL) containing K2CO3 (20.0 g, 2 equiv., 142 mmol). The mixture was stirred at ambien t temperature for 2 h. The organic phase was removed and the aqueous layer wa s extracted with additional CH2Cl2 (2x30 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to a small volume. Pentane was added slowly to precipitat e the free amine 5 (17.3 g, 86% from the salt) as a beige solid. 1H NMR (CDCl3): 6.74 (d, J =2.4 Hz, Ar-H), 6.63 (d, J =2.4 Hz, Ar-H), 6.45 (br s, ArOH), 5.30 (s, dithiane-H), 3.74 (br s, ArNH2), 3.11-3.01 (m, 2H), 2.95-2.88 (m, 2H), 2.24-

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61 2.14 (m, 1H), 2.01-1.86 (m, 1H), 1.25 (s, 9H). 13C NMR (CDCl3): 143.9, 140.9, 135.7, 122.4, 115.6, 114.3, 48.2, 34.3, 31.7, 31.6, 25.1. HRMS (EI): Theoretical 283.1065, Measured 283.1083. Anal. Calc. for C14H21NOS2: C, 59.55; H, 7.70; N, 4.97. Found C, 59.32; H, 7.47; N, 4.94. Synthesis of 3-4 To a solution of amine 3-3 (12.64 g, 44.7 mmol) in CHCl3 (125 mL) was added phenylisocyanate (4.85 mL, 1 equi v., 44.7 mmol). The solution was heated at reflux for 20 h, then cooled to ambient temperature. The solu tion was concentrated to approximately 1/3 the volume, and hexane was slowly added with stir ring. The off-white prec ipitate 3-4 (17.0 g, 95%) was filtered and washed with hexane. 1H NMR (DMSOd6): 9.26 and 9.24 (overlapping s, 2H), 8.34 (s, 1H), 7.80 (d, J =2.4 Hz, 1H), 7.45 (d, J =8.7 Hz, 2H), 7.28 (t, J =7.8 Hz, 2H), 7.09 (d, J =2.4 Hz, 1H), 6.99-6.95 (m, 1H), 5.70 (s, 1H), 3.12-3.04 (m, 2H), 2.90-2.86 (m, 2H), 2.15-2.10 (m, 1H), 1.80-1.69 (m, 1H), 1.23 (s, 9H). 13C NMR (DMSOd6): 153.3, 142.4, 140.2, 139.6, 128.8, 128.4, 126.4, 121.9, 118.7, 118.2, 117.1, 44.1, 33.9, 31.5, 31.3, 24.8. Anal. Calc. for C21H26N2O2S2: C, 62.25; H, 6.91; N, 6.66. Found C, 62.65; H, 6.51; N, 6.96. Synthesis of 3-5 To a mixture of 3-4 (9.0 g, 22.4 mmol) in AcOH (400 mL) was added SeO2 (12.4 g, 5 equiv., 112 mmol). The resulting mixture was sti rred at ambient temperature for 90 min during which time 3-4 was fully dissolved and a bypro duct precipitated. The mixture was filtered through a pad of Celite. The filter cake was washed with AcOH, and the filtrate was concentrated in vacuo to a solid. To the solid was added EtOAc and H2O, and the aqueous layer was basified with saturated K2CO3. The biphasic mixture was filtered again through Celite and the filtrate was transferred to a separatory funnel. The aqueous layer was extracted with EtOAc. The combined organics were wa shed with brine, dried (MgSO4), filtered and concentrated to a

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62 slurry. Hexane was added and the yellow-or ange precipitate (6.5 g, 93%) was filtered and washed with hexanes. The solid could be recrystallized from MeOH/H2O. An analytically pure sample was obtained by column chromatography (pen tane-ether 4:1) however the urea was used without further purification. 1H NMR (acetoned6): 11.34 (br s, OH), 9.98 (d, J=0.9 Hz, CHO), 8.77-8.74 (m, 2H), 7.93 (br s, 1H), 7.57-7.54 (m, 2H), 7.43-7.42 (m, 1H), 7.31-7.25 (m, 2H), 7.02-6.96 (m, 1H), 1.34 (s, 9H). 13C NMR (acetoned6): 198.6, 153.3, 148.5, 143.5, 140.6, 129.5, 129.1, 124.1, 123.0, 120.3, 119.3, 34.9, 31.5. HRMS (ESI-FT-ICR-MS) for [2M+Na]+ Theoretical 647.2840, Measured 647.2852; theoretical for [M+Na]+ 335.1366, measured 335.1372. Anal. calc. for C18H20N2O3: C, 68.84; H, 6.68; N, 8.71. Found C, 69.21; H, 6.45; N, 8.97. Synthesis of 3-6 A portion of 1.0 g (6.66 mmol) 1,2-diaminocyclohexane HCl was dissolved in 50 mL methanol. After dissolving 50 mL ethanol wa s added along with 3.0 g (6.33 mmol) of 3-(2,2Methylenebis (4-methyl-6tertbutylphenol)-5-methyl -2-hydroxybenzaldehyde. The reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the solid was washed with water, filtered and dried. The solid was dissolved in dry ether and a pale yellow solid precipitated which was filtered and dr ied to afford the produc t in an 82% yield (3.1 g). 1H NMR. 8.48 (s, 1H); 7.03 (s, 2H); 6.99 (s, 1H); 6.83 (s, 1H); 6.61 (s, 2H); 6.50 (s, 1H); 6.01 (s, 1H); 5.42 (bs, 2H); 5.09 (bs, 1H); 3.28 (m 1H); 2.75 (m, 1H); 2.19 (s, 9H); 1.71(m, 4H); 1.38 (s, 9H); 1.35 (s, 9H). 13C NMR 167.6; 157.41; 151.12; 150.64; 137.42; 137.20; 133.78; 130.62; 128.61; 127.48; 126.95; 126.53; 118.45; 70.01; 55.76; 38.16; 34.86; 34.64; 33.00; 29.93; 28.47; 23.78; 23.27; 21.19; 20.83. HRMS: Theoretical 571.3894; Measured 571.3894 [M Cl-].

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63 Synthesis of 3-7 A portion of 0.826 g (1.36 mmol) 3-6 was dissolved in 75 mL methylene chloride. To this solution was added 0.38 mL (2.72 mmol) of trie thylamine and 0.425 g (1.36 mmol) of 3-5 The reaction mixture was stirred overn ight at room temperature. The solution was poured into a separatory funnel and washed with a 1 M HCl so lution and then with wa ter. The solution was dried with sodium sulfate and the solvent was re moved. No attempt at further purification was made and the resulting crude product was used as the starting material in the synthesis of 3-8. Purification was performed afte r metalation of the complex. Synthesis of 3-8 A portion of 0.80 g 3-7 was dissolved in 100 mL of dry THF. To this solution was added 0.23 g nickel acetate and the reaction was stirred at room temperature for 2 hours. The solvent was removed under vacuum and the product was dissolved in pentane and filtered. The solvent was removed from the filtrate leaving a yellow / or ange solid. The solid was then washed with an excess of methanol yielding 0.200g of pure product (24% for two steps). 1H NMR: 8.62 (s, 1H); 8.33 (d, 1H); 7.03 (m, 12H); 6.90 (d, J = 6.6 Hz, 1H); 6.87 (s, 2H); 6.60 (s, 2H); 6.29 (s, 1H); 3.70 (bs, 1H); 3.29 (bs, 1H); 2.27 (s, 3H); 2.26 (s, 3H); 2.18 (s, 3H); 1.36 (s, 9H); 1.33 (s, 9H); 1.28 (s, 9H). 13C NMR 158.13; 157.94; 157.26; 152.58; 151.30; 150.67; 150.57; 138.86; 138.76; 138.55; 138.25; 135.38; 131.91; 130.87; 130.75; 130.40 130.33; 129.71; 129.11; 128.63; 127.22; 126.91; 126.52; 124.90; 122.25; 120.42; 119.94; 119.74; 119.08; 117.48; 70.79; 36.88; 34.82; 34.60; 34.19; 3 1.42; 30.02; 29.92; 29.45; 28.33; 28.14; 23.99; 21.29; 21.20. HRMS: Theoretical 921.4459; Measured 921.4487 [M + H+]. Anal. Calc. for C55H66N4O5Ni: C, 71.66; H, 7.22; N, 6.08. Found C, 71.44; H, 7.58; N, 5.79.

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64 ClO H Y445 HO S107 N H I356 N H O F357 O Figure 3-1. Schematic diagram of the open conformation of ClC chloride channel. Chloride is held in place by two OH-Cl hydrogen bonds from Y445 and S107. Figure 3-2. Schematic diagram of [2-2-F]-; a fluoride is hydrogen bonding with the four phenols of the anion receptor. HO Ni OH NN O O OH FHO H H [2-2-F]-

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65 Figure 3-3. Structure of salen based anion receptor with amine groups at the periphery. The receptor coordinates both cations and anions Figure 3-4. Synthetic scheme for compound 3-5. N N O O MII N N R R R R H H S O O O O 2OH O OH O NO2 OH NO2 S S OH NH2 S S OH H N S S O H N OH H N O O H N HNO3 HS SH BF3. OEt21.Fe,HAc 2.HCl 3.K2CO3PhNCO SeO2 AcOH 3-13-2 3-3 3-4 3-5

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66 H2N NH3Cl R= t -bu HO OH HO R R H O H "allup" NH3Cl N HO H R OH OH R OH O H N H N O N HO N HN HN O Ni OH NN R O O OH R H 3-8 HN O HN H NEt3Ni(OAc)2Ni OH NN R O O OH R H 2-Ni(II) HN O HN Bu4NCl ClOH OH R OH R 3-7 3-6 Figure 3-5. Synthetic scheme for the synthesi s of mixed phenolic-urea salen system (3-7), metalation at salen binding site and anion coordination (3-8).

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67 Figure 3-6. Titration plot of 3-7 with fluoride in acetone. There is a dramatic red shift in the absorption spectrum and also two well defined isobestic points.

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68 Figure 3-7. Depiction of the so lid-state structure (30% probab ility ellipsoids, carbons drawn with arbitrary radii) of [3-8-Cl]with chloride hydrogen bound to two phenols and two N-Hs from the urea. The tetrabut ylammonium cation and carbon hydrogens have been omitted for clarity. Selected distances: O(2)Cl(1) 3.158 ; O(3)CL(1) 3.108 ; N(3)Cl( 1) 3.512 N(4)Cl(1) 3.183

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69 CHAPTER 4 METAL SALEN UREA COMPLEXES AND THEI R HIGH AFFINITIES FOR THE HALIDES Introduction The use of N-H groups as hydrogen bond donor s is commonly employed in synthetic anion receptors11 as virtually all reported receptors focus on ligands incorporating groups such as amides, amines, pyrroles, and ureas.22 The urea group is among the most popular binding motifs in synthetic anion receptors si nce it offers two hydrogen bond donor groups aligned in the same direction, which are also the approp riate distance from one other to have strong interactions with a variety of anions including fluorid e, acetate, and phosphate among others.67 The synthetic ease in which ureas can be prepared also accounts fo r much of their diversity in a multitude of receptor systems (figure 4-1)48. Anion Receptor Systems Incorporating Ureas. Urea groups have been incorporated into multiple macrocyclic systems where molecular flexibility and cycle size impacts the anion binding affinity.69 Ureas have also been attached to va rious platforms in order to preorganize multiple urea groups.70 Preorganization of multiple ureas can lead to stronger hydrogen bonding than a single moiety as well as a potential incr ease in selectivity. Si nce ureas have two donors aligned in the same direction, arranging multiple groups in a manner to create a cavity affords the opportunity to have a high number of possible hydrogen bonding sites. Ureas have also been seen to adopt different geometries depending on the anion that it binds, making them versatile.71 For the development of anion receptors, it would seem that thiourea groups would be a better candidate because it is more acidic (pKa of 21.1) than urea (pKa of 26.9).72 Thioureas also have the advantage that they do not self associate as is often seen with ureas.73 Self association occurs when the N-H groups are hydrogen bonding to the carbonyl of another urea thus it is unavailable for anion coordination. Thioureas tend however, to deprotonate in the

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70 presence of most anions preventing their use as an effective receptor.74 In contrast ureas require a large excess of fluoride and using designed sy nthesis can prevent self associating from occurring.75 Metals have been used as a way to assemble urea groups for hydrogen bonding.76 The binding site can be regulated by the size and geomet rical preferences of the metal as well as the nature of the hydrogen bond donor substituent. The coordination of two ligands seen in figure 42, coordinate around a Cu2+ ion which then sets the position of the urea groups. The four N-Hs form a binding site that is th e appropriate size for the coordi nation of chloride. Binding constants were determined by UV-Vis spectros copy as the system offers strong absorption measurements due to the conjugation of the ligan d as well as the presence of a metal. The salen complexes discussed in chapters two and three have shown to be effective ways to induce anion coordination and the addition of me tals into the systems modulates the size of the binging cavity as well as offers a conveni ent way to monitor the binding event. Ureas are among the best hydrogen bond donor groups and we envisioned creating a purely urea based cavity attached to a metal salen backbone. Co mpound 3-8 has shown that ureas in combination with phenols are selective for fluoride and chlori de. The synthesis of a bis-urea receptor, its interactions with various anions as well as the effects of metal coordina tion and regulation of the size of the binding site are herein reported. Results and Discussion A simple Schiff base reaction with 1,2-diam ino-cyclohexane and tw o equivalents of 3-5 affords compound 4-1. The two urea groups attach ed to the salen backbone have four N-H donors (Figure 4-3), which are arranged into an anion binding cavity upon metalation with the diamagnetic and square planar metals Ni (II) (4 -2) and Pd (II) (4-3). Nickel and palladium behave similarly yet differ in ra dius by about 0.15 affording the opportunity to regulate the

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71 size of the binding cavity. The choice of metals allows the synthesis and the anion binding properties of the receptor to be monitored by NM R spectroscopy. Metalation of 4-1 occurs at the two salen imine nitrogens and the salen phenols bu t has no interaction with the urea N-Hs. Solid State Structures of Receptors. Both compound 4-2 and 4-3 were structurally characterized and studied. For the nickel comp lex 4-2, two symmetry independent molecules crystallized in the asymmetric unit and the stru cture is presented in figure 4-4. The average distance of the four Ni-oxygen bonds in the tw o complexes (1.835 ) are typical for a Ni(II) salen complex14 but significantly shorter than the corresponding average Pd-oxygen distances (2.021 ). The subtle size difference between th e two metals produces a profound increase in the separation between the two urea groups whic h has many consequences for the structure and anion binding ability of the two receptors. The relatively small size of square planar Ni(II) forces a significant distortion within the two arms. The phenyl rings on the urea, which w ould be expected to be coplanar due to the conjugated nature of the system, have an angle of 85 between them, which is likely caused by a steric clash between the phenyls. There is also a strong intr amolecular hydrogen bond between an N-H (N3) on one urea and the carbonyl (O4) of the second urea of the system with a short NH-O distance of 2.190 The salen urea ligand system (4-1) is highly conjugated and thus highly planar. In order to break the planarity and conjugation of the system, there is a high energy cost to pay that will only occur under certain circumstances such as in compound 4-2 causing one of the urea arms to bend. In contrast to compound 4-2, the Pd (II) com pound 4-3 crystallizes wi th only one molecule in the asymmetric unit and the distortions of th e urea arms are no longer observed (Figure 4-5). Since Pd (II) forms longer metal oxygen bonds th an Ni (II) with a concomitant increase in

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72 separation between the two extended arms. The ureas are oriented at a distance where the phenyl rings are coplanar and the formation of an intramolecular hydrogen bon d is less likely. Compound 4-3 crystallized with a water molecule in the pocket which is hydrogen bound to all four urea nitrogens at distances of 3.062 3.155 3.063 3.248 The small size of water allows it to lie within the plane of the urea mol ecule without causing distor tions to the receptor Anion binding properties of the two metal complexes were tested with n -Bu4N+ halide salts in a variety of solvents including acet one and DMSO, and both 4-2 and 4-3 show a high affinity for anions. As with compounds 2-2, 2-3 and 3-8 the binding constants of 4-2 and 4-3 for anions can be monitored by UV-Vis spectroscopy. The absorbance spectr um of 4-2 shows two strong MLCT transitions at 357 nm and 418 nm and the addition of fluoride to this solution induces a red shift in the spect rum with the main absorbance peaks shifting to 361 nm and 427 nm respectively (Figure 4-5). There is also thre e well defined isobestic point in the titration plot indicating a two state process. There is a considerably sm aller shift in the absorption spectra of 4-2 upon anion coordination than was seen with compounds such as 2-2 which contained phenolic substituents. The strongest absorbance of metal salen compounds is assi gned to the MLCT transition.54 The metal environments of compounds 2-2 and 2-3 are drastically altered by anion coordination. The most important being the change in geometry of the four phenols which much distort to accommodate the fluoride ion causing a distortion to the entire receptor including the salen backbone. In both 2-2 and 2-3, there were in tramolecular hydrogen bonds between the phenols and the phenolates of the salen bound directly to the metal. The addition of fluoride to the receptor disrupts the intramolecular hydrogen bonds of the phenols in order to coordinate to the anion. The electronic environment of the metal is altered and this contributes to the shift in the

PAGE 73

73 absorption spectrum. The colorimetric change s are less pronounced in 4-2 and 4-3 upon anion coordination; however, the binding event could be still be monitored, allowing the binding constant to be determined (Figure 4-6). The data obtained from the titration of 4-2 with tetrabutylammonium fluoride affords the binding constant Log Ks = 6.10, which is high and indicative of the strong interactions between fluoride and the ureas. To determine this binding constant, the data from the titration was plotted as a function of the equation: X = X0 + [(Xlim X0) / 2c0] [c0 + cm +1/Ks [(c0 + cM + 1/Ks)2 4c0cM]1/2] and a non-linear least squares regr ession was performed to find the Ks value that best fits the data (Figure 4-7). While 4-2 has shown to have st rong interactions with fluoride, the anion binding properties of the receptor were tested with other larger anions such as chloride and bromide. Both chloride and bromide coordinate to this system with hi gh binding constants and ther e is also a trend in relative binding constants which is consistent wi th observations of the structures in the solid state. The urea receptors have limited flexibility and the site of the binding cavity is determined by the particular metals that are coordinated to the salen. The pref erence for a particular anion is determined by geometry, size and the comp atibility of the anion and receptor. Compound 4-2 is able to coordina te chloride and this complex (4-4) has been structurally characterized giving insight into the binding mode as well as th e effect this has on the binding constants (Figure 4-8). Size limitations of the binding cavity force the chloride to reside above the plane of the molecule. The structure shows that all four urea nitr ogens are hydrogen bonding to the chloride at distances of N(3)Cl(1) 3.490 ; N(4)Cl(1) 3.255 ; N(5)Cl(1) 3.601 ; N(6)Cl(1) 3.130

PAGE 74

74 The N-H groups are all slightly distorted and pointing towards the ani on since chloride is too large to be positioned any clos er to the receptor. Each urea arm is splayed out as far as possible in order to limit the amount of distortions that break the planarity and conjugation of the molecule. The hydrogen bond distances from N(3) and N(5) are longer than the other two nitrogens because they are dir ectly connected to the rigid salen backbone and have limited flexibility. The hydrogen bond distances from N(4) and N(6) to the chloride are significantly shorter as the molecule is more flexible at this position and these two N-Hs are able to twist and point directly at the chloride. The solid state structure shows the chloride i on sitting above the plan e of the molecule and directly adjacent to the anion is a highly diso rdered tetrabutylammonium cation. Packing plots show that there is only one receptor bound to each anion in the solid state and Job plots indicate a 1 : 1 complex in solution (Figure 4-9). Job plots are prepared by measuring differences in absorption or chemical shifts of a series of so lutions at various concentrations of anion and receptor, and these changes are monitored by NMR and UV-Vis spectroscopy. Due to the large changes in absorption spectra, UVVis spectroscopy was used for the creation of Job plots for 22 and 2-3. For the urea based recep tors however, the shifts in th e N-H peaks were distinct and the changes were monitored at different concentra tions leading to a Job polt indicating there is a one to one, receptor to anion binding mode. The solid state structure of compound 4-2 with a bound brom ide ion has been obtained (Compound 4-5) and there are severa l structural differences to the receptor upon coordination of bromide versus chloride. The larger size of bromide causes it to be positioned high above the plane of the molecule and th e hydrogen bond distances between the ureas and the bromide are longer than those of 4-4 with distance s of N(3)Br(1) 3.616 ; N(4)Br(1) 3.208 ;

PAGE 75

75 N(5)Br(1) 3.576 ; N(6)Br(1) 3.358 The long receptor-bromide distances force significant distortions in the planar ity of the molecule. The distortion is not only seen in the urea groups which must bend upwards to coordinate the bromide, but is also translated to the salen backbone which has an 11.8 angle between the tw o nitrogen, oxygen, nickel planes [N(1), O(1), Ni(1) and N(2), O(3), Ni(1)]. The structure al so shows a disorder in the urea containing N(5), N(6) and O(4), with the receptor taking two sligh tly different angles as a means of coordinating bromide. The receptor is trying to minimize the di stortion caused as it is unfavorable to break the receptors planarity a nd conjugation, but in order to coordinate bromide some distortions must occur. The addition of chloride or bromide to a solu tion of 4-2 leads to sim ilar titration plots as seen with fluoride with a red shift in the abso rption spectra and three di stinct isobestic points (Figure 4-10). From the titration data, the bind ing constants were determined (Figure 4-11) and there was a correlation between these constants and the hydrogen bond lengths. While 4-2 is a strong receptor for both chloride (log Ks = 5.27) and bromide (log Ks = 4.29), there is an order of magnitude difference in the binding constants. Chlo ride is able to form a more stable complex with the 4-2 than with bromide because of its smaller size and ability to be positioned close to the receptor. While it is seen that the relative size of the anion plays an important role in the coordination process, the spatial constraints of th e receptor can be modified to make adjustments to the anion coordination process. Compound 4-3 possesses a urea cleft that is larger than the one in compound 4-2 which is caused by the inco rporation of Pd (II). The binding mode of chloride and bromide as seen in the solid states in compounds 4-4 and 4-5 indicate the anions is positioned considerably above the plane of the mo lecule. Since 4-3 situates the two urea groups

PAGE 76

76 further apart, it enables the anions to be posit ioned closer to the receptor and would possibly have an effect on the binding constants. To determine the anion binding properties of 4-3 NMR and UV-Vis spectra were taken. The NMR spectrum showed distinct shifts in the positions of the urea N-Hs upon addition of fluoride, chloride and bromide. The UV-Vis spectra followed similar trends to that of 4-2. Upon addition of various halides there was a red shift in the absorbance with two isobestic points. The binding constants of 4-3 were determined with the UV-Vis titration data and were found to be logKs = 6.09 for fluoride, logKs = 5.53 for chloride and logKs = 4.67 for bromide. There is approximately an order of magnitude decrease in the binding efficiency of fluoride and chloride and that of chloride and bromide. The biding constants of both 4-2 and 4-3 decreas e with an increase in anion size (Table 41). Both receptors show simila r binding constants for fluoride as it is the smallest anion tested and spatial constraints would not be as significan t of a factor. The binding constants for the larger anions chloride and bromide are higher for receptor 4-3 than 4-2, consistent with the larger separation of ureas allowing the anions to be pos itioned closer to the receptor. The ability to adjust the size of the system by the incorporation of different metal centers into the salen macrocycle creates a tunable system as which is demonstrated by the differences in binding constant data for 4-2 and 4-3. While the urea based salen receptors are very efficient halide binders, the addition of a third urea arm could maximize the selectivity of the system for certain anions and still maintain the high binding constants seen wi th 4-2 and 4-3. The addition of a third urea arm would create a three dimensional pocket that would force the anion to be positioned inside the cavity. The structure of the C3 symmetric receptor would have all three urea groups pointing inwards

PAGE 77

77 preventing anions from residing above the plane of the molecule. Using a modified literature procedure78 various salen type C3 symmetric ligands could be crea ted with the tris-amine TREN [Tris(2-aminoethyl)amine] and used to coor dinate various lantha nides (Figure 4-13). The initial work focused on the addition of lu tetium to the tris-urea receptor because it is a diamagnetic metal which allows the synthesis and anion binding properties to be followed by 1H NMR spectroscopy. Lutetium is th e smallest of the lanthanides and coordination of different larger metal centers could change the receptors size and binding properties, but a urea receptor incorporating any other lanthanide was not isolated. A solid stat e structure of 4-6 was obtained (Figure 4-14) and it shows the coordination mode of the metal center as well as the orientation of the urea groups. The structure shows that th e Lu (III) is seven coordina te, bonding to the three imine nitrogens and three phen olic oxygens as well as forming a bond with the apical nitrogen on tren N(1). The coordination of lutetiu m sets the geometry of the ureas and forms a cavity that was less flexible and more size selective for anions. The solid state structure shows an intramolecular hydrogen bond between the proton on N(10) and O( 4) at a distance of 2.846 as well as hydrogen bond between N(3), N(4) and a water molecule. Anion binding studies of 4-6 were do ne with various anions by both 1H NMR and UV-Vis spectrum. There was no change in the NMR or UV-Vis spectrum with Br-, I-, NO3 -, ClO4 indicating no interaction with the receptor, but it was able to bind chloride. There was however a change to the absorbance spectrum upon addition of chloride and a bi nding constant of logKs = 4.45 was determined in acetone. The addition of fluoride to 4-6 causes a demetalation of the complex as noted by both the UV-Vis and 1H NMR spectral data. Demetalation of the complex

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78 limits its ability to be used as an anion recepto r and this phenomenon has been seen in previous work in the group with other syst ems incorporating lanthanides. To create a system that does not demetala te upon the addition of anions, an unreactive metal center must be incorporated. Co (III) is an inert metal that should be extremely stable in an octahedral environment. The tetra-amine tren used for the formation of 4-6 was ideal for the coordination of large metals such as the lantha nides due to its size and ability to coordinate through four nitrogens. To bind the sm aller Co (III) the tris-amine tame [1,1,1tris(aminoethyl)methane] was used to coordinate first row transition metals because they prefer to be six coordinate. The ligand synthesis and metalation of the system is summarized in Figure 4-15. For the metalation reaction, Co (II) ace tate is the source of the metal and upon coordination to the ligand it is oxidized to Co (III) with a dilute solu tion of peroxide. The procedure for metalation must be followed as th e direct addition of iner t Co (III) to the ligand would not be an effectiv e means of metalation. A solid state crystal structure was obtai ned for 4-8 which crystallized as a C3 symmetric molecule (Figure 4-16). The Co (III) metal center is six coordinated and orie ntates the three urea groups into a cavity with all six N-Hs aligned in the same direc tion. There is a twist throughout the entire molecule, from the imines to the ureas, as seen in the solid state structure, but the configuration of the molecule is expected to be dynamic in solu tion. Differences in the lutetium (4-6) and the cobalt (4-8) receptors are mainly a result of the size difference between the two metals. The average Lu O bond is 2.168(8) while the average Co O bond is 1.896(16) and the difference is translated to th e urea groups and the binding cavity. The anion binding properties of 4-8 were test with n -Bu4N+ halide salts and the addition of bromide and iodide to the receptor caused no changes in the UV-Vis or 1H NMR spectra

PAGE 79

79 indicating that the addition of a third urea arm has placed size constraints on the binding cavity and increased the selectivity of the urea system for smaller anions. Once again the coordination of anions causes a red shift in the absorbance spectrum from which binding constants were obtained. Binding constants of log Ks = 5.00 for fluoride in DMSO and log Ks = 4.95 in acetone were determined, while chloride had a binding constant log Ks = 4.02 in acetone, but did not bind in DMSO. Conclusions The incorporation of urea groups onto a metal salen macrocycle has shown to be an efficient anion sensor. The urea groups have bound halides with high binding constants which are directly proportional to the hydrogen bond lengths of the receptor to the anion. The receptors formed 1 : 1 complexes with the anions as conf irmed by both solid state and solution studies. By changing the metal that is coordinated at the sa len binding site, the recept ors binding ability can be altered by changing the position of the urea groups. Besides structural considerations, the metals strong MLCT transitions and color also supply the means to monitor the binding of anions by UV-Vis spectroscopy due to strong MLCT transitions and the color allow the binding constants to be determined. For compounds 4-2 and 4-3 anion coordination occurs at the pe riphery of the receptor as the anion must be positioned above the plane of th e molecule for an intera ction to take place. Adjustments to the size of the binding cavity can relegate the effectiveness in which coordination occurs, but can not exclude the coor dination of certain anions by spat ial constraints. To increase the selectivity of the system for certain anions, a third urea arm wa s added to the receptor. Using Lu (III) as the metal template proved ineff ective however, as demetalation occurred upon the addition of certain anions. Instead, it was determin ed that Co (III) formed stable complexes with a C3 symmetric ligand system and proved to be a sele ctive binder of fluoride and chloride solely.

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80 The biding constant of 4-6 is higher than that of 4-8 for chloride which may be a result of the larger cavity that is formed as Lu (III) is larger than Co (III). Experimental Methods General Considerations 1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at 299.95 and 75.47 MHz for the proton and carbon cha nnels. UV-Vis spectra were recorded on a Varian Cary 50 spectrometer. All solvents were ACS or HPLC grade and used as purchased. For the metalation reactions, the solvents were dr ied with a Meyer Solvent Purification system. Some starting materials were synthesized by other members in the group. All NMR spectra are taken in CDCl3 unless otherwise stated. Some structur es are not fully characterized and the experimental procedures reflect known data obt ained to date for these compounds. Tame was synthesized by Priya Srinivasan, and 35 was synthesized by Melanie Veige. Synthesis of 4-1 A 1.0 g portion (3.23 mmol) of 3-5 was dissolved in 50 mL of absolute ethanol. To this solution was added 0.184 g (1.61 mmol) of trans1,2-diaminocyclohexane. The reaction was refluxed open to the air for 12 hours. The soluti on was cooled to room temperature and 50mL water was added to the solution resulting in the pr ecipitation of a bright or ange solid. The solid was filtered and dried to afford th e product in 76% yield (0.86 g). 1H NMR: 9.36 (s, 2H); 8.51 (s, 2H); 8.29 (t, J = 2.7 Hz, 4H); 7.45 (s, 2H); 7.43 (s, 2H); 7.26 (t, J = 8.1 Hz, 6H); 6.95 (t, J = 7.5 Hz, 2H); 6.89 (d, J = 2.4 Hz, 2H); 3.54 (s, 2H); 2.02-1.40 (m, 8H); 1.20 (s, 9H). 13C NMR 165.7; 152.5; 151.8; 139.8; 139.0; 128.8; 128.5; 121.7; 119.8; 118.5; 118.0; 115.1; 68.8; 33.8; 32.1; 31.1; 23.5. HRMS: Theoretical 703.3966; Measured 703.4008.

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81 Synthesis of 4-2 A portion of 0.5 g (0.712 mmol) of 4-1 was dissolved in 75mL of dry THF. To this solution 0.177 g (0.712 mmol) of nickel acetate was adde d and it was refluxed under nitrogen for 12 hours. The solution was cooled, filtered and th e solvent removed. The solid was then washed with pentane and filtered producing a red solid produc t in a 84% yield (0.45g). Crystals suitable for X-ray diffraction were grown by a diffusion of ether into a saturated acetone solution. 1H NMR: 8.22 (s, 2H); 7.84 (bs, 4H); 7.45 (m, 4H); 7.18 (s, 2H); 7.08 (t, 4H); 6.92 (m, 2H); 6.62 (s, 2H); 3.76 (m, 2H); 3.10 (m, 2H); 2.24 (m, 2H); 1.82 (m, 4H); 1.23 (s, 18H). 13C NMR 199.28; 158.60; 138.61; 128.82; 122.81; 122.19; 120.10; 118.75; 70.15; 34.20; 31.59; 28.96; 24.51. HRMS: Theoretical [M + Na] 781.2983; Measured 781.3002. Anal. Calc. for C42H48N6O4Ni: C, 66.41; H, 6.37; N, 11.06. Found C, 66.13; H, 6.39; N, 11.00. Synthesis of 4-3 A portion of 0.5 g (0.712 mmol) 4-1 was dissolved in 75 mL of dry diethyl ether. To this solution 0.0824 g (1.56 mmol) sodium methoxide was added along with 0.195 g (0.783 mmol) of palladium acetate. The solution was refluxe d for 12 hours under nitrogen during which time a green precipitate formed. The solution was c ooled and the precipitate was filtered. The product was redissolved in methylene chloride, filtered and then solvent was removed leaving a yellow solid in a 48% yield (0.28 g). X-ray quality crystals were grown by a chloroform/pentane diffusion. 1H NMR. 9.20 (s, 2H); 8.56 (s, 2H); 8.51 (d, J = 2.4 Hz, 2H); 8.12 (s, 2H); 7.46 s, 2H); 7.43 (s, 2H); 7.21 (s, 2H); 7.17 (m, 4H); 6.97 (t, J = 7.5 Hz, 2H); 3.55 (m, 2H); 2.75 (m, 4H); 1.82 (m, 2H); 1.49(m, 2H); 1.28 (s, 18H). 13C NMR 157.48; 152.50; 151.34; 139.50; 136.31; 130.08; 128.56; 122.53; 121.87; 118.85; 118.48; 118.41; 72.23; 33.78; 31.30; 28.33; 24.05. HRMS: Theoretical [M + Na] 829.2676; Measured 829.2679.

PAGE 82

82 Synthesis of 4-6 A portion of tren 0.157 g (1.08 mmol) was dissolved in 10 mL methanol. To this solution was added 0.390 g (1.08 mmol) lutetiu m triflate. The solution was then heated to 50 c and stirred open to air for 15 minutes. A 1.0 g portion (3.23 mmol) of 1-(5tert -butyl-3-formyl-2hydroxyphenyl)-3-phenylurea was then dissolved in 25 mL of methanol, added to the solution and stirred for 15 minutes. The solution was th en filtered and allowed to slowly cool and evaporate. After sitting for 12 hours large x-ray quality crystals had grown. These crystals were filtered, crushed, and dried yielding a brig ht yellow powder in 45% yield (0.58 g). 1H NMR: 8.15 (s, 3H); 8.02 (m, 3H); 7.36 (s, 6H); 7.20 (m 6H); 7.13 (m, 6H); 6.90 (m, 3H); 6.84 (m, 3H); 3.95 (m, 3H); 3.22 (d, 3H); 2.89 (m, 6H); 1.12 (s, 27H). 13C NMR 169.5; 156.3; 154.7; 139.0; 137.7; 129.9; 129.0; 124.2; 123.1; 120.6; 119.5; 60.1; 58.3; 34.1; 31.5. ). HRMS: Theoretical [M + H] 1201.4882; Measured 1201.4898. Synthesis of 4-7 A 1.0 g portion (3.23mmol) of 3-5 was dissolved in 50 mL of absolute ethanol. To this solution was added 0.087 g (1.08 mmol) of tame. The reaction was refluxed open to the air for 12 hours. The solution was cooled to room temper ature and filtered. To the filtrate was added 50 mL of water resulting in the precipitation of a bright orange solid. The solid was filtered and dried to afford the product in 80% yield (0.86 g). 1H NMR in DMSO: 9.36 (s, 3H); 8.62 (s, 3H); 8.39 (s, 6H); 7.45 (d, 6H); 7.26 (t, 6H); 7.024 (d, 3H); 6.95 (t, 3H); 3.67 (s, 6H); 1.27 (s, 27H); 1.18 (s, 3H). HRMS: Theoretical [M + H] 1000.5389; Measured 1000.5444. Synthesis of 4-8 A portion of 1.50 g (1.50 mmol) of 4-7 was disso lved in 15mL ethyl acetate. To this solution a solution of 0.75g (3.00 mmol) of cobalt( II) acetate tetrahydrate in 50mL methanol was added. A 3% solution of hydroge n peroxide (10 mL) was then added. The solution was then

PAGE 83

83 brought to a boil for 5 min. The solution and suspended solid was then extracted with chloroform (3 times 100 mL each). The extracts were washed several times with water, dried with sodium sulfate and the solvent removed to afford the product in a 52% yield (0.818 g). Crystals suitable for X-ray diffraction were grown by an acetone / pentane diffusion. 1H NMR: 7.91 (s, 3H); 7.74 (s, 3H); 7.56 (s, 3H); 7.27 (s, 3H); 7.23 (s, 3H); 7.05 (t, J = xx, 6H); 6.91 (s, 3H); 6.82 (t, 3H); 3.74 (d, 3H); 3.39 (d, 3H); 1.13 (s, 3H); 1.09 (s, 27H). 13C NMR 167.9; 155.5; 153.0; 139.4; 135.2; 131.1; 128.3; 122.6; 121.6; 121.0; 119.9; 118.2; 63.7; 40.6; 33.5; 31.0; 20.4. HRMS: Theoretical 1056.45; Measured 1056.45. Anal. Calc. for C59H66N9O6CoH2O : C, 65.96; H, 6.38; N, 11.74. Found C, 65.30; H, 6.48; N, 10.70.

PAGE 84

84 Table 4-1. LogKs values of the two salen urea complexes with fluoride, chloride and bromide in acetone. Compound 4-2 Compound 4-3 F6.10 6.09 Cl5.27 5.53 Br4.29 4.67 Table 4-2. X-ray data from crystal structures of 4-2, 4-3, 4-4, 4-6, 4-8. 4-2 4-3 4-4 4-6 4-8 total reflections unique reflections max crystal system space group a () b () c () ( ) ( ) ( ) Vc (3) Z 19062 9861 28 triclinic P-1 12.3151(6) 17.2793(8) 20.9637(9) 107.0500(10) 92.9510(10) 95.3330(10) 4231.9(3) 2 9871 6718 28 monoclinic I2/a 17.6232(10) 17.2988(9) 28.011(2) 90.00 94.4040(10) 90.00 8514.3(9) 4 13587 6020 28 monoclinic c2/c 43.56(3) 10.203(5) 26.868(16) 90.00 91.67(7) 90.00 11938(12) 6 16723 12542 28 monoclinic P2(1)/c 15.0435(13) 25.384(2) 19.0081(17) 90.00 94.287(2) 90.00 7238.2(11) 6 4240 4015 28 triclinic P 28.0319(11) 28.0319(11) 28.0319(11) 90.0 90.0 90.0 22027.1(15) 16

PAGE 85

85 Figure 4-1. Proposed structure and binding mode of an early urea based anion receptor.68 Figure 4-2. Structure of a ur ea subunit where the anion bindin g cavity is regulated by metal coordination N N N H O N H CF3 N O N H H O O

PAGE 86

86 Figure 4-3. Synthetic scheme for the formation of salen urea (compound 4-1) Figure 4-4. Depiction of the solid-state struct ure of 4-2 (30% probabi lity ellipsoids, carbons drawn with arbitrary radii). The break in planarity of the urea group N5, O4, N6 is caused by a steric clash between the two phenyl rings as well as an intramolecular hydrogen bond between N3 and O4. OH H N O H N O 2Eq. H2N NH2 N N HO HN O HN OH NH O NH

PAGE 87

87 Figure 4-5. Depiction of the solid-state struct ure of 4-3 (30% probabi lity ellipsoids, carbons drawn with arbitrary radii) The two urea groups are orie nted to form an anion binding cavity with four N-H groups available for hydrogen bonding

PAGE 88

88 Figure 4-6. UV-Vis titration of 4-2 with tetra-bu tylammonium fluoride in acetone. Titration was complete after the addition of a single equivalent of fluoride.

PAGE 89

89 Figure 4-7. Binding constant da ta of 4-2 titrated with Fat 450nm Log Ks = 6.10. Each point represents an experimental value and the best fit line is shown where a value of Ks is calculated to minimize the error to the system.

PAGE 90

90 Figure 4-8. Depiction of the solid-state struct ure of 4-4 (30% probabi lity ellipsoids, carbons drawn with arbitrary radii, tetrabutyl ammonium cation and hydrogen removed for clarity). The chloride is positioned above the plane of the molecule and the four urea N-Hs are distorted in order to be aligned with the anion.

PAGE 91

91 Figure 4-9. Job plot of 4-2 for chloride. An apex in the plot at 0.5 indicated that there is a 1 : 1 ratio of anion to receptor in complex 44. [L] = concentration of receptor; [A] = concentration of anion; = NMR chemical shift.

PAGE 92

92 Figure 4-10. Depiction of the so lid-state structure of 4-5 (30% probability ellipsoids, carbons drawn with arbitrary radii, tetrabutyl ammonium cation and hydrogen removed for clarity). The bromide is positioned above the plane of the molecule and the four urea N-Hs are distorted in order to be aligned with the anion.

PAGE 93

93 Figure 4-11. UV-Vis titration of 4-2 with tetrabutylammonium chloride in acetone. Titration was complete after the addition of a single equivalent of fluoride.

PAGE 94

94 Figure 4-12. Binding constant data of 4-2 titrated with Clat 450nm Log Ks = 5.27. Each point represents an experimental value and the best fit line is shown where a value of Ks is calculated to minimize the error to the system.

PAGE 95

95 Figure 4-13. Synthetic scheme for compound 4-6. The metal Lu (III) is fi rst reacted with tren and then the condensation reaction with the urea aldehyde to afford compound 4-6. O HN O HN N 3 N Lu N H2N NH2 NH2 OH H N O H N O 3Eq. 1.)Lu(III)triflate2.)

PAGE 96

96 Figure 4-14. Depiction of the so lid-state structure of 4-6 (30% probability ellipsoids, carbons drawn with arbitrary radii, hydrogens and water molecu le removed for clarity).

PAGE 97

97 Figure 4-15. Synthesis of ligand 4-7 and C3 symmetric anion receptor 4-8. NH2 H2N NH2 OH H N O H N O 3Eq. HO HN O HN N N N HO HN OH NH O HN O HN Co(OAc)2H2O2 O HN O HN N Co 3 + 4-7 4-8

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98 Figure 4-16. Depiction of the so lid-state structure of 4-8 (30% probability ellipsoids, carbons drawn with arbitrary radii, tetrabutyl ammonium cation and hydrogen removed for clarity).

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99 CHAPTER 5 DESIGNER LEWIS ACIDS; THE DEVELOPM ENT OF EXREMELY BULKY AND RIGID DINUCLEAR CHIRAL CATALYSTS Introduction Metal salen compounds are used in a many cataly tic systems as they are able to promote a variety of organic transformations.79, 80 Salens are formed by a condensation reaction between salicylaldehyde and a diamine and are able to co ordinate many different metal centers in a wide range of oxidation states. Chiral salen catalysts are readily prepared with enantiomerically pure diamines, are adept at a number of enantiose lective reactions such as alkene epoxidation,81 and the Diels Alder reaction,82 among numerous others.83 For the design of chiral catalys ts, the geometry of the salen is essential to determine the orientation of the substrate upon coordination to the binding site. Metals bound within the salen are able to transfer their ch irality to the products by binding the substrate through Lewis acidic interactions. The approach of the substrate towa rds the catalyst and the metal center influences the conformation of the product. In the design of asymmetric catalys ts, it is important to control the trajectory of the substrate.79 The conformation of the activ e site is influenced by many factors including the size and oxi dation state of the coordinating metal. The nature of the ligand also plays an important role as the location and st eric constraints of the substituents on the salen can regulate the path of approach of the substrate.84 Jacobsens Catalyst Jacobsens catalyst is perhaps the most influential and well known metal salen compound (Figure 5-1) and it contains a Mn (III) metal center for the asymmetric epoxidation of olefins.81 Although chromium was used ear ly to epoxidize olefins,85 Jacobson found manganese to be a superior choice for this reaction as it proceeds through a Mn (V) oxo species.86 The generally accepted catalytic cycle, depicted in Figure 5-2, involves two steps. In the first, the oxidant

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100 transfers and atom to oxidize Mn (III) to Mn (V) oxo and this species reacts with the incoming olefin to create the epoxide. The source of oxygen for the epoxidations is typically iodosylbenzene, but other oxygen sources such as bleach or peroxide are also catalytically competent. Many different chiral diamines such as binapthylene87 and diphenyl88 are used as catalyst backbones, but 1,2-diaminocyclohexane is among th e most commonly used, due to the low cost of the chiral form. A second generation Jacobsen type catalyst, with chir al diphenyl diamine and binapthyl groups combines their chiral elements to influence the stereosel ectivity of the reaction (figure 5-3) .89 Not only do the bulky chiral groups influe nce the approach of the substrate to the catalyst, but they cause a folding effect, altering the geometry at the metal center. Lewis Acid Catalysts Since chiral metal salens are able to transmit their geometry onto substrates they are often employed as Lewis acid catalysts for many organic transformations. The Friedel-Crafts reaction, the ene reaction, and Diels-Al der reaction employ ordinary Lewis acids such as AlCl3, TiCl4 and BF3.90 Although these reactions proceed very e fficiently; they are neither regio nor stereoselective. Many biologically active molecu les are chiral and the design of asymmetric catalysts to facilitate carbon carbon bond formation is of part icular importance to medicinal chemistry and the pharmaceutical industry because many of their products require 99% enantiomeric excess (e.e.).92 Modifying the ligands coordinate d to the Lewis acidic metal can lead to products with highe r regio and enantioselectivity. Zn Salens in Catalysis Chiral Zn salen compounds can catalyze ster eoselective organic transformations. For example, a Lewis acidic Zn (II) can promote effi cient addition of an ethyl group to aldehydes with ees ranging from 35-70 %.93 Unfortunately, the isolation of a pure metalated Zn (II) salen

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101 is often problematic, and mixtures of me talated product and free ligand are obtained.79 To overcome this challenge, metalation of the salen occurs in situ with Et2Zn, and the resulting complex catalyzed at 10 mol. % to promote the a ddition of an ethyl group to benzaldehyde. The proposed reaction mechanism involves the simu ltaneous coordination of the aldehyde and Et2Zn to the Lewis acidic Zn salen. The manner in whic h the aldehyde orients itself when coordinating to the metal center influences the stereochemistry of the product. The hydrogen atom of the aldehyde aligns itself in order to minimize its interactions with the stereo centers. Bifunctional Zn salen catalysts that cont ain both a Lewis acid and a Lewis base component can promote the addition of an ethyl group to benzaldehyde with high efficiency and stereoselectivity.94 The Lewis acidic Zn metal center coordinates and activ ates the aldehyde, while the aminoalkoxy groups at th e periphery of the salen are ab le to coordinate and activate diethylzinc (Figure 5-5). Once activated, the s ubstrates have an enhanced reactivity for the addition of diethylzinc to al dehydes with respect to other Zn salen catalyst systems.93 While numerous methods promote asymmetric reactions with aldehydes, there are only a handful of examples of reactions with ketones, which are generally considered to be unreactive as substrates in asymmetric catalysis.95 Ketones are difficult s ubstrates due to their low reactivity as well as problems c ontrolling their stereoselectivity.95 A Zn salen catalyst can facilitate the stereoselective a ddition of terminal alkynes to a mu ltitude of ketones with moderate yields (30-90 %) and enantiomeri c excess (30-81 %) (Figure 5-6).96 For the reaction to proceed, a zinc alkynide forms in situ and associates with the salen ph enolates. The ketone, which is coordinated to the Lewis acidic Zn salen site, is then able to add the alkyne and a diagram of the proposed transition state is depicted in figure 5-7.

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102 The Promotion of the Diels-Alde r Reaction by a Lewis Acid The Diels-Alder reaction, which is one of th e most widely used reactions in synthetic organic chemistry can be fac ilitated by Lewis acid catalysts.97 While Diels-Alder reactions can occur in the absence of a catalyst without stereose lectivity, at high temperature, the presence of a chiral Lewis acid can initiate th e reaction with higher selectivit y. Among the chiral Lewis acid catalysts able to promote the Diels-Al der reaction are organic iminium salts,98 and metal salen complexes containing Co (III)99 or Cr (III).100 General Approaches of Synthetic Design Although the work in the field of asymmetric catalysis is vast, there is always the need to create systems that are more efficient and selectiv e. Designer Lewis acidic catalysts can promote a variety of organic transformations and particular interest has b een paid to the development of catalysts that can induce regioand stereoselective products.101 The nature of the ligand as well as the metal are crucial to the reactivity and sele ctivity of any catalyst, and modifications made to the system can influence its properties. Herein, we report the design and synthesis of an extremely bulky and rigid chiral Lewis acid catalyst. Results and Discussion For the design of Lewis Acidic catalysts, the salen macrocycle offers a convenient way to create a system compatible with many different metal centers to promote a variety of organic transformations. The presence of rigid and st erically bulky groups on the salen can enhance stereoselectivity by blocking the ca talytic site from substrate a ttack. Metal salen compounds are ideal candidates for Lewis acid catalysts since th ey can facilitate many reactions efficiently and selectively with metals such as Ti, Cr Al, Co, and Zn among numerous others.79 The environment of the metal affects stereoselectivity as the chirality at the metal center can translate to the products.

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103 Previous work with chiral metal salen com pounds in the Scott lab has shown that four phenols at the periphery of a sa len can be orientated into a tetrahedral environment as in compound 2-2.63 In the solid stat e structure of 2-2, R,R1,2-diaminocyclohexane is chiral, but this geometry is not translated to other parts of the ligand. The bulky phe nols still have a lot of rotational freedom and their position is not influe nced by the chirality of the diamine. In the solid state structure, two molecu les crystallized in the asymmetric unit, each with a different orientation of the phenols, indicatin g that the configuration of the system would not be useful as a chiral catalyst (Figure 5-9). Binap Ligand In order to design a system where the chiral unit of the structur e would translate its geometry to the entire molecule, it must possess a larger torsion angle than R,R -1,2diaminocyclohexane. Binapthylene is a common moiety in many catalytic systems. It is chiral and has a large angle between the two napthyl planes (Figure 5-10). The condensation of 2,2diamino-1,1-binapthylene with a portion of an aldehyde derivative of triphenoxymethane 5-1 affords compound 5-2 as depicted in Figure 5-11. Both chiral and racemic versions of ligand 5-2 were synthesized and there are not ed differences in the properties of the two. The condensation reaction of the racemic compound readily forms th e product (5-2), but the chiral portion does not cleanly convert to the desired product and column chromatography must be employed to isolate the ligand (5-3). Once isolated both molecules have identical NMR and absorption spectra, but have strikingly different solubili ties. While 5-2 is soluble in onl y a handful of solvents such as THF, methylene chloride and chloroform, compound 5-3 was sol uble in all organic solvents ranging from pentane to methanol. The ability to manipulate a liga nds solubility is often impor tant for the development of catalysts as metalation reactions of salens often require the pr ecipitation of the complex as a

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104 means of isolating the product. Ligands which ar e extremely soluble will create difficulties in the formation of the catalyst. In order to attempt to lower the solubility of the chiral system the alkyl groups on the triphenoxymethane were changed from tbutyl to methyl groups which would presumably diminish the compounds solubili ty in non-polar solvents. Both the racemic (5-4) and chiral (5-5) versions of the di-methyl derivative were made and a depiction of the synthetic scheme for the formation of 5-4 can be seen in figure 5-12. The incorporation of the methyl groups did sl ightly decrease the sol ubility of the ligand and a solid state structure of 54 was obtained (Figure 5-13). The structure shows that there is a significant angle between the two napthyl planes of 98.6, which should force the geometry of the entire molecule upon metalation. Unlike the st ructure of 2-1, there is a well defined twist in the structure of the binap derivative and it is this twist that is critic al to the design of our catalyst. Racemic Zn Catalyst All initial work in catalyst design involved th e use of the racemic versions of the molecules due to the lower cost of the starting diamine. The first area of concentration included the metalation of the binap ligands with Zn (II). Zinc salens are useful as Lewis acid catalysts, and have many useful properties including no redox ac tivity or air sensitivity. Zn (II) also is diamagnetic offering the ability to monitor the synthesis by 1H NMR spectroscopy. Metalation of 5-2 and 5-4 with Zn(II) followed typical lite rature procedures by precipitating from an acetonitrile solution upon metal complexation102 to form the methyl and the tbutyl derivatives 56 and 5-7 respectively. In solid state structure 5-6, the binapthylene influences the geom etry of the entire molecule (Figure 5-14). On each side of the structure, the phenols are orientated in the opposite direction of the napthyl plane. There is a distinct tw ist to the molecule creating a channel in which substrates could coordinate. There is enough sp ace around the catalytic site for a substrate to

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105 bind as the solid state structure has two THF solv ent molecules coordinated to the Zn (II) metal center, intimating the Lewis acid properties of the Zinc salen species. The majority of Zn salen molecules are five coordinate,103 however, there are a few examples of six104 and four105 coordinate complexes. In the presence of a c oordinating solvent such as THF, the metal center of 5-6 assumes an octahedral geometry with th e two THF molecules in the axial positions and the four binding sites of the sa len coordinating in the equatori al positions. The zinc oxygen and zinc nitrogen distances of 5-6 ar e typical for Zn (II) binap salen compounds.106 The solid state structure of 5-6 was obtaine d in the coordinating solvent THF, but a structure of 5-7 was obtained from a soluti on of the non-coordinating solvent methylene chloride. There is a drastic difference between th e two structures as the lack of a coordinating solvent completely changes the geometry of the metal (figure 5-15). The metal center of 5-7 is aligned in a tetrahedral geometry and the position of the four phenols is also quite different since they are spaced much further apart. There is a greater twist to th e structure of 5-7 than there is for 5-6, but in both cases the geometry of the enti re molecule is determined by the position of the binaphthalene. The zinc oxygen and zinc n itrogen distances of 5-7 are typical for Zn (II) binap salen compounds,106 while the geometry is a distorted te trahedral with N(1) Zn(1) N(2) angles of 96.6(4), and O(1) Zn (1) O(4) andgles of 116.4(3). While the position of the four phenols is influe nced by the binaphthalene in the sold state, these bulky groups contain a large degree of rotational freedom and would be dynamic in solution. In order for an asymme tric catalyst to be effective, it must be able to force the stereochemistry of the substrate. The extremel y bulky groups, as seen in this system on the periphery of the salen, could be an ideal means to do this, yet if the phenols are not rigidly locked into position it will not be effective. Th e four phenols are aligned in a pseudo tetrahedral

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106 array and the incorporation of anot her metal at this site would lock them into position creating an extremely bulky and rigid multinuclear catalyst wh ich would not be flexib le in solution. Ti (IV) will form complexes with four phenol s arranging the phenolates into a tetrahedral geometry.107 Since these complexes are d0, the products can be readily observed by 1H NMR spectroscopy. Initial attempts at metalation involving TiCl4 and triethylamine as a base for the deprotonation of the phenols were unsuccessful as a mixture of products was obtained. The addition of one equivalent of titanium isopropoxide to a solution of 5-7 however, led to a clean conversion to the desired catalyst 5-8 and a depiction of the solid state structure can be seen in figure 5-16. The incorporation of titanium not only rigidi fies the system, but creates a channel for substrate coordination to occur. The oxygen t itanium bond lengths in the range of 1.799(2) to 1.828(2) are typical for a Ti (IV) atom bound to four phenolates in a tetrahedral environment204 and the titanium is very near this geometry with angles ranging from 104.3(10) to 118.8(11). The phenol that includes O(3) is a ligned in a manner that blocks an entire side of the metal center from substrate attack and in co mbination with the binaphthalene group forms an ideal site for asymmetric catalysis to occur. Spac e filling models of 5-8 infer that the presence of the t-butyl groups on the phenols is importa nt to create the proper ster ic constraint to force the stereoselectivity of the products (F igure 5-17). After this observan ce, no further effort was made with ligand 5-4. Zinc behaves as a Lewis acid and coordinates a THF solvent molecule to one side of the zinc in comparison to the structur e of 5-6 which coordina tes two THF molecules; however, compound 5-8 only binds one solvent mol ecule because of the rigidity and steric constraints placed on the system. The metal center is in a trigomal bipyramidal geometry as the angle of O(1) Zn1 O(4) is 128.92(13) and the angle of O(1) Zn(1) N(1) is 90.25(10).

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107 Chiral Zn Catalyst The synthesis of the target catalyst has proven th e plausibility of the system, but in order to be an effective asymmetric catalyst, a chiral mol ecule must be isolated, but the metalation of 5-3 with Zn (II) proved difficult. The synthesis of compound 5-6 involved th e precipitation of the product from the reaction mixture u pon metalation. Due to the high so lubility of 5-3, the chiral complex never precipitated from the reaction mixt ure and all attempts to purify the mixture were unsuccessful. A multitude of reaction conditions a nd purification techniques were screened with none resulting in better than a 60 : 40 ratio of metalated compound to free ligand as determined by 1H NMR spectroscopy. Difficulties in isola ting chiral Zn salen compounds have been previously noted with a mixture between th e metalated and free ligand species being the common product.79 Most systems employ an in situ metalation method with alkyl zincs such as Et2Zn,93, 94 but this is not a possibility for a multinucle ar system as the Zn product must first be isolated. Co Catalysts Since the isolation of a chiral Zn catalyst pr oved difficult, other metals were examined. Both Co (II) and Co (III) are useful in asymmetr ic catalysis and have been able to promote organic reactions with high efficiency and selectivity.109 Co salen compounds can enantioselectively facilitate the Baeyer-Villiger oxidation,110 as well as the Diels-Alder reaction99 in good yields. The metalation of ligand 5-2 with Co (II) afforded the product 5-9. Although Co (II) is paramagnetic, the compound synthesis could be monitored by 1H NMR spectroscopy. (Figure 5-18). In order to rigidify the system, titanium was once again coordinated to the four phenols to lock in the geometry. The positions of the phe nols have been influenced by the binaphthalene and the solid state structure of this complex (5-10) is isostructural to that of 5-8. The ionic radii

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108 of Zn (II) (0.880 ) and Co (II) (0.885 ) are near ly identical and the similarity is directly translated to the structure (Figure 5-19). The metal ligand bond lengths are similar to other Co (II) binaphthalene salen complexes,111 and both the bond lengths and angles from the titanium to the phenolates are typical.108 Much like the Zn (II) system, th e isolation of a chiral Co (II) was problematic due to the high solubi lity of the complex, and it became apparent that in order to isolate a chiral metal salen catalyst, the so lubility of the ligand had to be altered. Low Solubility Chiral Ligands As a starting point for the formation of le ss soluble triphenoxymethane aldehydes, the substituent in the R3 position of the molecule was changed (Figure 5-20). Both 2,6-diformyl-4bromophenol and 2,6-diformyl-4-nitrophenol are known,112 and the incorporation of either the bromo or nitro group to the system decreased th e solubility of the molecule. The synthetic scheme for the triphenoxymethane aldehyde com pounds can be seen in figure 5-21 and both the bromo (5-11) and the nitro (5-12) derivatives were readily isolated. The condensation reaction of R,R(+)-2,2-diamino-1,1-binapthyl ene and the aldehydes 511 and 5-12 afforded the chiral ligands 5-13 a nd 5-14 (Figure 5-22). The solubility of the ligands in polar and non-polar solvents is consid erably lower than that of complexes 5-3 and 5-5, and the isolation of the chiral Le wis acid catalysts is attainable. The addition of a large excess of Co (II) to 5-13 and 5-14 in methanol led to th e precipitation of the pure compounds 5-15 and 516 respectively. While the metalation of 5-13 w ith Zn (II) was unsuccessful the addition of a large excess of the metal to 5-14 fo stered the clean conversion to 5-17. In the solid state structure of 5-16, Co (II) is in an octahedr al geometry with four bonds from the salen ligand and two coordinating metha nol molecules (Figure 5-24). The coordination of methanol to the metal center has an effect on the solubility of th e compound, as the reaction does not cleanly convert to product in other solv ents. While other compounds in this chapter

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109 have crystallized as a single enantiomer, 5-16 wa s the first structure of a metalated enantiopure compound with R-(+)-2,2-diamino-1,1-binapthale ne as a backbone. The four phenols of compound 5-16 are rigidified by the addition of titanium created an extremely bulky and rigid chiral, Lewis acid catalyst (5-18). Initial Catalysis Studies Throughout the process of catalyst developmen t, the ability of the metal complexes to facilitate organic transformations has been monito red as a means to judge the feasibility of the system. The standard reaction used to determin e catalyst activity was th e addition of an ethyl group to benzaldehyde. In order fo r this reaction to occur, a Lewi s acid catalyst must be present and there are many examples of Zn salen systems promoting this reaction in high yields (Figure 5-25).93 The catalytic ability of the racemic Zn (II) (5 -8) and Co (II) (5-10) complexes were tested and both were able to transform the reaction in quantitative yields (96-98 %). There was no indication of any remaining benzaldehyde in the 1H NMR spectrum of the crude product. The reaction mixture contains both th e alcohol product and the catalyst, but upon workup the catalyst can be recovered and reused in other reactions. The reactivity of 5-7 and 5-9 was also examined and not surprisingly they both were also able to promote this reaction. The absence of the titanium should have little impact on the reactivity at the Lewis acid site, but rather is important to lock in the chiral geometry of th e system to increase enantioselectivity. Conclusions The ability to devise new asymmetric cataly sts is of great importance to the field of synthetic organic chemistry. For this purpose, a class of multinuclear salen based, chiral Lewis acid catalysts have been developed. Both Zn (II) and Co (II) derivatives have been made and initial studies have indicated th at they are able to promote th e ethyl addition to benzaldehyde.

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110 The reactivity of the system with countless other reactions has still yet to be explored. The chirality of the system is determined by the bina p group as its large torsion angle is able to set the geometry of the entire compound. The additi on of titanium to coordinate to the four phenols is able to rigidify the molecule and lock in the chirality. Experimental Methods General Considerations 1H and 13C NMR spectra were recorded on a Varian Mercury 300 MHz spectrometer at 299.95 and 75.47 MHz for the proton and carbon cha nnels. UV-Vis spectra were recorded on a Varian Cary 50 spectrometer. Elemental analyses were performed at either the in-house facility of the Department of Chemistry at the Univ ersity of Florida or by Complete Analysis Laboratories Inc., Parsippany, NJ. All solven ts were ACS or HPLC grade and used as purchased. For the metalation reactions, the solvents were dried with a Meyer Solvent Purification system. Synthesis of 5-2 A portion of 1.00 g (3.52mmol) of racemic 1,1-B inapthyl-2-2-diamine was dissolved in 250 mL absolute ethanol. To this solution a portion of 3.34 g (7.04 mmol) of 5-1 was added. The reaction was refluxed open to the air for 12 hours. The solution was cooled to room temperature and water was added to the solution resu lting in the precipitati on of an orange solid. The solid was filtered and dried to afford the product in 90% yield (3.81 g). Crystals suitable for X-ray diffraction were grown by a THF / pentane diffusion. 1H NMR: 13.20 (s, 2H); 8.49 (s, 2H); 8.12 (d, 2H, 9.3 Hz); 7.00 (d, 2H, 8.7 Hz); 7.46 (m, 2H); 7.29 (m, 6H); 7.05 (s, 2H); 6.98 (s, 2H); 6.93 (s, 2H); 6.78 (s, 2H); 6.65 (s, 2H); 6.56 (s, 2H); 5.63 (s, 2H); 5.4 2 (s, 2H); 5.07 (s, 2H); 2.19 (s, 6H); 2.14 (s, 6H); 2.12 (s 6H); 1.45 (s, 18H); 1.32 (s, 18H). 13C NMR 161.9; 155.8; 151.4; 151.2; 143.8; 137.7; 137.4; 135.1; 133.2; 132.9; 131.6; 130.7; 129.3; 128.9; 128.8;

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111 128.7; 128.4; 128.1; 127.6; 127.5; 127.4; 127.3; 127.0; 126.9; 126.8; 126.3; 199.1; 117.0; 37.1; 35.1; 34.9; 30.1; 30.0; 21.3; 20.7. Anal. Calc. for C82H88O6N2: C, 82.37; H, 7.26; N, 2.34. Found C,82.10; H, 2.61; N, 2.21. Synthesis of 5-3 A portion of 1.00 g (3.52mmol) of R -(+)-1,1-Binapthyl-2-2-dia mine was dissolved in 250 mL absolute ethanol. To this solution a por tions of 3.34 g (7.04 mmol) of 5-1 was added. The reaction was refluxed open to the air for 12 hour s. The solution was cooled and the solvent removed under vacuum. The solid was dissolved in the minimum amount of methylene chloride and filtered through a plug of alumina. The solv ent was then removed to afford the product in 75% yield (3.14 g). 1H NMR: 13.20 (s, 2H); 8.49 (s, 2H); 8.12 (d, 2H, 9.3 Hz); 7.00 (d, 2H, 8.7 Hz); 7.46 (m, 2H); 7.29 (m, 6H); 7.05 (s, 2H); 6 .98 (s, 2H); 6.93 (s, 2H); 6.78 (s, 2H); 6.65 (s, 2H); 6.56 (s, 2H); 5.63 (s, 2H); 5.42 (s, 2H); 5.0 7 (s, 2H); 2.19 (s, 6H); 2.14 (s, 6H); 2.12 (s, 6H); 1.45 (s, 18H); 1.32 (s, 18H). 13C NMR 161.9; 155.8; 151.4; 151.2; 143.8; 137.7; 137.4; 135.1; 133.2; 132.9; 131.6; 130.7; 129.3; 128.9; 128.8; 128.7; 128.4; 128.1; 127.6; 127.5; 127.4; 127.3; 127.0; 126.9; 126.8; 126.3; 199.1; 117.0; 37.1; 35.1; 34.9; 30.1; 30.0; 21.3; 20.7. HRMS: calcd for C82H88O6N2 1197.6715; found 1197.6715 [MH+]. Synthesis of 5-4 A portion of 1.00 g (3.52mmol) of racemic 1,1-B inapthyl-2-2-diamine was dissolved in 250 mL absolute ethanol. To this solution a portion of 2.75 g (7.04 mmol) of 3-(bis(2-hydroxy3,5-dimethylphenyl)methyl)-2-hydro xy-5-methylbenzaldehyde was added. The reaction was refluxed open to the air for 12 hours. The soluti on was cooled to room temperature and water was added to the solution resulting in the precipit ation of a pink solid. The solid was filtered and dried to afford the product in 87% yield (3.14 g). 1H NMR: 13.22 (s, 2H); 8.44 (s, 2H); 8.07 (d,

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112 2H, 9 Hz); 7.98 (d, 2H, 8 Hz); 7.51 (d, 2H, 9 Hz); 7.46 (t, 2H, 8 Hz); 7.25 (t, 2H, 9 Hz); 6.93 (s, 2H); 6.88 (s, 2H); 6.82 (s, 2H); 6.72 (s, 2H); 6.65 (s 2H); 6.59 (s, 2H); 5.7 1 (s, 2H); 5.38 (s, 2H); 5.10 (s, 2H); 2.26 (s, 6H); 2.18 (s, 6H); 2.15 (s, 6H); 2.14 (s, 6H ); 2.11 (s, 6H). 13C NMR 162.1; 156.1; 150.4; 143.6; 134.5; 133.5; 133.3; 1 32.8; 131.5; 130.6; 130.5; 129.3; 129.2; 129.2; 129.1; 128.9; 128.7; 128.2; 127.4; 127.2; 126.9; 126.1; 125.6; 125.4; 119.1; 117.0. HRMS: calcd for C70H64O6N2 1029.4837; found 1029.4794 [MH+]. Synthesis of 5-5 A portion of 1.00 g (3.52mmol) of R-(+)1,1-B inapthyl-2-2-diamine was dissolved in 250 mL absolute ethanol. To this solution a portions of 2.75 g (7.04 mmol) of 3-(bis(2-hydroxy3,5-dimethylphenyl)methyl)-2-hydro xy-5-methylbenzaldehyde was added. The reaction was refluxed open to the air for 12 hours. The reac tion was cooled and the solvent was removed under vacuum. The solid was dissolved in the minimum amount of methylene chloride and filtered through a plug of neutral alumina with a 90:10 methylene chloride:methanol mixture. The solvent was removed to afford an orange solid in 71% yield (2.57 g). 1H NMR: 13.22 (s, 2H); 8.44 (s, 2H); 8.07 (d, 2H, 9 Hz); 7.98 (d, 2H, 8 Hz); 7.51 (d, 2H, 9 Hz); 7.46 (t, 2H, 8 Hz); 7.25 (t, 2H, 9 Hz); 6.93 (s, 2H); 6.88 (s, 2H); 6.82 (s, 2H); 6.72 (s, 2H); 6.65 (s, 2H); 6.59 (s, 2H); 5.71 (s, 2H); 5.38 (s, 2H); 5.10 (s, 2H); 2.26 (s, 6H); 2.18 (s 6H); 2.15 (s, 6H); 2.14 (s, 6H); 2.11 (s, 6H). 13C NMR 162.1; 156.1; 150.4; 143.6; 134.5; 133.5; 133.3; 132.8; 131.5; 130.6; 130.5; 129.3; 129.2; 129.2; 129.1; 128.9; 128.7; 128.2; 127.4; 127.2; 126.9; 126.1; 125.6; 125.4; 119.1; 117.0. HRMS: calcd for C70H64O6N2 1029.4837; found 1029.4794 [MH+]. Synthesis of 5-6 A portion of 0.25 g (0.24 mmol) of racemic 54 was dissolved in a minimum amount of methylene chloride. To this solution was adde d 200 mL of acetonitrile as well as a portion of 0.059 g (0.27 mmol) of Zinc acetate 2 H2O. The solution was stirred and heated at 75 C for

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113 four hours. A yellow precipitate forms and the so lid was filtered and dried to afford the product in 82% yield (0.21 g). Crystals suitable for X-ray diffraction were grown by a THF / pentane diffusion. 1H NMR: 8.33 (s, 2H); 8.06 (d, 2H, 9 Hz); 7.88 (d, 2H, 9 Hz); 7.45 (s, 2H); 7.42 (m, 2H); 7.21 (m, 4H); 6.86 (d, 2H, 12 Hz); 6.81 (s, 2H ); 6.78 (s, 6H); 6.71 (s, 2H); 6.64 (bs, 2H); 6.38 (s, 2H); 6.33 (bs, 2H); 2.14 (s, 6H); 2.11 (s, 6H); 2.03 (s, 6H). Unable to obtain 13C NMR due to low solubility. HRMS: calcd for C70H62O6N2Zn 1091.3972; found 1091.3870 [MH+]. Synthesis of 5-7 A portion of 2.00 g (1.67 mmol) of racemic 52 was dissolved in a minimum amount of methylene chloride. To this solution was adde d 200 mL of acetonitrile as well as a portion of 0.46 g (2.10 mmol) of Zinc acetate 2 H2O. The solution was stirred and heated at 75 C for four hours at which time a yellow precipitate forme d. The solid was filtered and dried to afford the product in 89% yield (1.87 g). 1H NMR: 8.32 (s, 2H); 8.00 (d, 2H, 8.7 Hz); 7.89 (d, 2H, 8.7 Hz); 7.43 (m, 4H); 7.21 (m, 4H); 6.96 (m, 6H); 6.89 (d, 2H, 8.7 Hz); 6.82 (d, 4H, 7.8 Hz); 6.77 (s, 2H); 6.29 (s, 2H); 6.07 (s, 2H); 2.18 (s, 6H); 2.12 (s, 12H); 1.38 (s, 18H); 1.24 (s, 18H). 13C NMR 171.3; 164.4; 152.1; 152.0; 144.7; 139.2; 137.5; 137.4; 135.0; 134.1; 133.8; 132.4; 131.4; 128.7; 128.5; 128.3; 128.1; 127.4; 127.3; 127.0; 126.6; 126.5; 126.4; 126.0; 125.7; 125.3; 121.4; 118.1; 35.1; 34.9; 30.1; 29.9; 21.3; 21.2; 20.4. HRMS: calcd for C82H86O6N2Zn 1259.5730; found 1259.5850 [MH+]. Synthesis of 5-8 A portion of 0.50g (0.39 mmol) of 5-7 was partia lly dissolved in 50 mL of dry methylene chloride under nitrogen. To this solution was added a portion of 0.12 g (0.44 mmol) titanium isopropoxide. The solid instantly dissolved into the solution which turned dark red. The solution was allowed to stir for 12 hours in the dry box at which time the solvent was removed in vacuum yielding pure product in 95% yield (0.49 g). Crystals suitable for X-ray diffraction

PAGE 114

114 were grown by a pentane diffusion into an acetonitrile / THF solvent mixture. 1H NMR: 8.21 (s, 2H); 7.95 (d, 2H, 9 Hz); 7.85 (d, 2H, 9 Hz); 7.58 (s, 2H); 7.39 (t, 2H); 7.14 (t, 2H); 7.02 (s, 2H); 7.00 (s, 2H); 6.79 (s, 2H); 6.75 (d, 2H); 6.70 (s, 4H ); 5.84 (s, 2H); 2.39 (s 6); 2.22 (s, 6H); 2.15 (s, 6H); 1.40 (s, 18H); 0.99 (s, 18H). 13C NMR 170.2; 170.0; 160.4; 160.3; 145.4; 140.9; 137.1; 135.8; 134.8; 134.7; 134.1; 132.2; 130.9; 130.7; 130.6; 129.2; 128.3; 127.0; 126.7; 126.5; 126.3; 125.8; 125.7; 123.8; 123.7; 121.9; 117.4; 65.8; 44.1; 35.5; 34.5; 30.4; 30.0; 29.7; 25.4; 22.5; 21.2; 21.1; 20l6; 15.3; 13.9. Synthesis of 5-9 A portion of 1.00 g (0.84 mmol) of racemic 52 was dissolved in 50 mL of methylene chloride. A portion of 0.266 g (1.07 mmol) of cobalt(II) acetate 4 H2O was dissolved in the minimum amount of methanol under nitrogen. The cobalt solution was added to the ligand solution under nitrogen and stirred for two hours. A red /orange precipitate formed and was quickly filtered and dried to affo rd the product in 87% yield (0.92 g). 1H NMR: paramagnetic signals 59.75; 53.98; 40.96; 15.69; 12.88; 9.13; 8.32; 7.77; 5.79; 3.87; 2.27; -1.67; -4.83; -10.3; -50.87. HRMS: calcd for C70H62O6N2Co 1254.5891; found 1254.5818 [M-H]+. Synthesis of racemic 5-10 A portion of 1.00 g (0.79 mmol) of racemic 5-9 was partially dissolved in 50 mL of dry methylene chloride under nitrogen. To this solution was added a portion of 0.24 g (0.87 mmol) titanium isopropoxide. The solid in stantly dissolved into the solution which turned dark red. The solution was allowed to stir for 12 hours in the dry box at which time the solvent was removed in vacuum yielding pure product in 92% yield (0.95 g). Crystals suitable for X-ray diffraction were grown by a pent ane diffusion into an acetonitrile / THF solvent mixture. 1H NMR: 64.56; 61.92; 46.92; 15.02; 11.79; 9.25; 7.55; 7.23; 7.17; 6.09; 5.28; 4.77; 4.05; 3.70; 3.48; 2.34; 1.84; 1.02; 0.87; -4.43; -4.80; -7.25; -7.84; -12.12; -48.1

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115 Synthesis of 5-11 A portion of 1 g (4.37 mmol) of 2,5-diformyl-4 -bromo-phenol was added to a portion of 1.79 g (10.9 mmol) of 2-t-butyl-4-methyl-phenol. To this was added the minimum amount of trifluoroacetic acid needed to fully dissolve the so lids. The reaction was a llowed to stir at room temperature for 12 hours at which point a white so lid precipitated. Cold methanol was added to the reaction mixture and the produc t was filtered. The filtrate was taken and the solvent removed under vacuum to yield a solid which was the wash ed with cold methanol affording more pure product. The product was a white solid and was afforded in 76 % yield (1.8 g). 1H NMR: 11.40 (s, 1H); 9.89 (s, 1H); 7.68 (s, 1H); 7.33 (s, 1H); 7.07 (s, 2H); 6.54 (s, 2H); 5.99 (s, 1H); 2.20 (s, 6H); 1.38 (s, 18H). 13C NMR 195.7; 158.1; 151.0; 140.2; 137.8; 134.9; 133.91; 129.9; 127.8; 127.3; 126.5; 121.7; 112.0; 39.3; 34.7; 30.0; 21.3 HRMS: calcd for C30H35O4Br 538.1719.; found 538.1680. Synthesis of 5-12 A portion of 2.00 g (10.24 mmol) of 2,5-diformyl-4-nitro-phenol was added to a portion of 4.20 g (25.6 mmol) of 2t -butyl-4-methyl-phenol. To this was added the minimum amount of trifluoroacetic acid needed to fu lly dissolve the solids. The reacti on was allowed to stir at room temperature for 12 hours at which point a white so lid precipitated. Cold methanol was added to the reaction mixture and the produc t was filtered. The filtrate was taken and the solvent removed under vacuum to yield a solid which was the wash ed with cold methanol affording more pure product. The product was a white solid and was afforded in 44 % yield (2.3 g). 1H NMR: 12.05 (s, 1H); 10.0 (s, 1H); 8.52 (d, 1H, 2.7 Hz); 8.22 (d, 1H, 2.7 Hz); 7.10 (s, 2H); 6.52 (s, 2H); 6.08 (s, 1H); 2.22 (s, 6H); 1.39 (s, 18H). 13C NMR 195.8; 163.9; 150.0; 140.9; 137.7; 133.6; 131.9; 130.1;128.5; 128.0; 127.4; 127.3; 126.4; 1 19.3; 116.6; 39.5; 34.7; 30.1; 29.8; 21.3 HRMS: calcd for C30H35O6N + Na 528.2357.; found 528.2359 [M+Na]+

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116 Synthesis of 5-13 A portion of 0.50 g (1.75 mmol) of R -(+)-1,1-Binapthyl-2-2-diamine was dissolved in 150 mL absolute ethanol. To this solution a portion of 1.84 g 511 was added. The reaction was refluxed open to the air for 12 hours. A pale or ange precipitate had formed and was filtered which was pure product. The solvent of th e filtrate was removed under vacuum and the remaining solid was dissolved in the minimu m amount of methylene chloride and filtered through a plug of alumina. The solvent was then removed and the combination led to a combined 68% yield (1.59 g). 1H NMR: 13.42 (s, 2H); 8.51 (s, 2H); 8.11 (d, 2H, 9 Hz); 7.99 (d, 2H, 9 Hz); 7.60 (d, 2H, 9 Hz); 7.49 (t, 2H, 9 Hz); 7.34 (m, 2H); 7.18 (d, 4H, 9 Hz); 7.06 (s, 2H); 7.00 (s, 2H); 6.57 (s, 2H); 6.51 (s, 2H); 5.60 (s, 2H); 5.19 (s, 2H); 4.96 (s, 2H); 2.18 (s, 6H); 2.15 (s, 6H); 1.43 (s, 18H); 1.34 (s, 18H). 13C NMR 160.1; 157.3; 151.1; 151.0; 142.6; 137.7; 137.6; 136.7; 133.2; 133.1; 133.0; 131.5; 130.9; 129.8; 129.4; 129.3; 128.8; 127.5; 127.3; 127.1; 127.0; 126.9; 126.8; 126.7; 120.6; 116.4; 111.0; 37.3; 35.0; 34.9; 30.1; 30.0; 21.3; 21.2. HRMS: calcd for C80H82O6N2Br2 1325.4618.; found 1325.4368 [MH+]. Synthesis of 5-14 A portion of 0.475 g (1.67mmol) of R -(+)-1,1-Binapthyl-2-2-diamine was dissolved in 150 mL absolute ethanol. To this so lution a portion of 1.63 g (3.33 mmol) of 5-12 was added. The reaction was refluxed open to the air for 12 hours. The reaction was cooled and the solvent was removed under vacuum to afford the product in 97% yield (2.04 g). 1H NMR: 14.65 (bs, 2H); 8.71 (s, 2H); 8.14 (m, 4H); 7.99 (m, 2H); 7.93 ( d, 2.4 Hz, 2H); 7.84 (m, 2H); 7.68 (d, 9 Hz, 2H); 7.52 (m, 2H); 7.34 (m, 2H); 7.23 (m, 4H); 7.07 (s, 2H); 7.03 (s, 2H); 6.85 (m, 2H); 6.57 (s, 2H); 6.51 (s, 2H); 6.48 (s 2H); 5.65 (s, 2H); 2.14 (s, 6H); 7.13 (s, 6H); 1.42 (s, 18H); 1.39 (s, 18H). 13C NMR 166.1; 159.4; 151.0; 150.9; 104.3; 139.5; 137.7; 133.4; 137.7; 133.4; 133.1; 132.3; 131.4; 129.7; 129.5; 129.4; 129.2; 128.9; 128.7; 128.0; 127.5; 127.3; 127.1;

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117 127.0; 126.9; 126.8; 126.7; 126.6; 117.2; 116.6; 115.8; 37.9; 34.9; 34.8; 30.1; 30.0; 29,8; 21.3. HRMS: calcd for C80H82O10N4 1259.6104 .; found 1259.6134 [M+H]+ Synthesis of 5-15 A portion of 0.50 g (0.40 mmol) of 5-14 was di ssolved in 150 mL methanol. To this solution a large excess of C obalt acetate 1.00 g (4.00 mmol) was added. The reaction was brought to a boil under nitrogen at which point the heat was remove d and the reaction was stirred for 4 hours. A brown precipitate had formed a nd was quickly filtered to afford the pure product in 81% yield (0.84 g). 1H NMR: 59.51; 53.39; 18.70; 16.81; 12.95; 9.13; 8.18; 7.06; 5.83; 4.61; 3.90; 2.92; 2.15; 1.90; 1.52; 1.32; 0.8 6; -1.18; -3.39; -5.49; -7.99; -9.61; -14.80; -53.96. HRMS: calcd for C80H80O10N4Co 1315.5201; found 1315.5205. Synthesis of 5-16 A portion of 1.00 g (0.75 mmol) of 5-13 was dissolved in 150 mL methanol. To this solution a large excess of C obalt acetate 1.88 g (7.70 mmol) was added. The reaction was brought to a boil under nitrogen at which point the heat was remove d and the reaction was stirred for 4 hours. A brown precipitate had formed a nd was quickly filtered to afford the pure product in 81% yield (0.84 g). 1H NMR: 60.20; 55.46; 16.04; 12.86; 10.50; 9.06; 8.37; 7.55; 6.97; 5.79; 5.43; 4.91; 3.50; 2.07; 1.79; 1.35; 1.2 6; -1.01; -1.49; -2.95; -3.15; -4.51; -10.39; -51.76. HRMS: calcd for C80H80O6N2Br2Co 1382.3793; found 1382.3448 [MH+]. Synthesis of 5-17 A portion of 0.50 g (0.40 mmol) of 5-14 was di ssolved in 150 mL methanol. To this solution a large excess of Zinc acetate 1.00 g ( 4.00 mmol) was added. The reaction was brought to a boil under nitrogen at which point the heat was removed and the reaction was stirred for 4 hours. A yellow precipitate had formed and was qui ckly filtered to afford the pure product in 54% yield (0.285 g). 1H NMR: 8.44 (s, 2H); 8.07 (m, 6H); 7.97 (d, 2H, 9 Hz); 7.48 (t, 2H, 7.5

PAGE 118

118 Hz); 7.32 (d, 2H, 9 Hz); 7.00 (s, 4H); 6.90 (d, 2H, 9 Hz); 6.76 (s, 2H); 6.54 (s 2H); 6.21 (s, 2H); 5.94 (s, 2H); 5.42 (s, 2H); 2.19 (s, 6H); 2.13 (s, 6H); 1.34 (s, 18H); 1.28 (s, 18H). 13C NMR 172.4; 170.3; 151.0; 150.9; 144.0; 138.1; 136.9; 136.7; 133.6; 132.5; 132.3; 131.5; 130.0; 129.7; 129.5; 128.7; 128.4; 127.9; 127.6; 127.4; 127.2; 126.8; 126.6; 126.5; 125.5; 121.2; 117.2; 37.8; 35.0; 34.8; 30.1; 21.3; 21.1. HRMS: calcd for C80H80O10N4Zn 1320.5106; found 1320.5119.

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119 Figure 5-1. Structure of Jacobs ens catalyst used for the as ymmetric epoxidation of olefins N N O O Mn O N N O O Mn Cl R O R NaOCl NaCl Figure 5-2. Proposed mechanism for the epoxida tion of olefins with Jacobsens catalyst. N N O O Mn Cl

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120 Figure 5-3. Structure of catalyst with chiral binapthyl groups that influence the geometry of the substrate. Figure 5-4. Reaction scheme for the ethyl addition to benzaldehyde The reaction is promoted by the chiral Lewis acidic Zn-salen catalyst. Figure 5-5. Structure of a bif unctional catalyst containing both a Lewis acid and Lewis base component. N N O O Mn PhPh N N O O Zn O Et2Zn OH N N O O Zn N N O O LewisAcid LewisBase

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121 Figure 5-6. Schematic diagram of the en antioselective alkyna tion of ketones. Figure 5-7. Proposed transition st ate for the alkynation of ketones with a zinc salen catalyst Figure 5-8. Diels-Alder reacti on between cyclopentadiene and cinnamaldehyde promoted by a Lewis acid catalyst. N N O O Zn O Me2Zn OH R H R N N O O Zn Zn Ph O R O CHO Ph Catalyst+

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122 Figure 5-9. Solid state structure of compound 2-2. The chirality of the cyclohexane ring does not affect the position of the four phenols. Figure 5-10. Depiction of 2,2diamino-1,1-binapthalyene show ing the large torsion angle between the two napthyl planes. NH2 NH2 NH2NH2

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123 Figure 5-11. Synthetic scheme for the synthesis of 5-2. Figure 5-12. Synthetic scheme for the formation of 5-4. The tbutyl groups of the triphenoxymethane have been replaced by methyl groups. N OH HO OH NH2 H2N OH O HO OH +2Eq. 5-1 5-2 H N HO OH HO N OH HO OH NH2 H2N OH O HO OH +2Eq. 5-4 H N HO OH HO

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124 Figure 5-13. Solid state struct ure of compound 5-4 (30% probab ility ellipsoids for nitrogen and,oxygen; carbons drawn w ith arbitrary radii)

PAGE 125

125 Figure 5-14. Solid state struct ure of 5-6 with two THF solven t molecules coordinated to the zinc. The geometry of the napthyl rings se ts the position of the four phenols. (30% probability ellipsoids for zinc, nitroge n and oxygen; carbon atoms drawn with arbitrary radii, non coordinated solven ts and hydrogen atoms were removed for clarity)

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126 Figure 5-15. Solid state struct ure of compound 5-7. Without th e presence of a coordinating solvent, the metal center takes a tetrahedra l geometry. (30% probability ellipsoids for zinc, nitrogen and oxygen; carbons drawn with arbitrary radii, solvents and hydrogen atoms were removed for clarity)

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127 Figure 5-16. Solid state structure of the dinuclear catalyst 5-8. A Zn (II) metal is coordinated in the salen binding site and Ti (IV) is coor dinated to the four phenols creating a rigid structure. (30% probability ellipsoid s for zinc, titanium, nitrogen and, oxygen; carbon atoms drawn with arbitrary radii; THF and acetonitrile solvent molecules and hydrogen atoms were removed for clarity)

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128 Figure 5-17. Space filling models of the solid stat e structure of 5-8. The catalytic site of Zn (II) is represented in purple (right), and the chiral cavity formed for possible substrate binding can clearly be seen. The titanium is deeply buried in the phenolic pocket (left) Figure 5-18. 1H NMR spectrum of the paramagnetic compound 5-9 in CDCl3.

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129 Figure 5-19. Solid state structur e of the dinuclear compound 5-10 Figure 5-20. Schematic of triphenoxymethane al dehyde showing its possible positions for ligand modification. R 3 OH O HO R1 R2 OH R1 R2 H

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130 Figure 5-21. Synthetic scheme for compounds 5-11 and 5-12 Figure 5-22. Synthetic scheme fo r the synthesis of 5-13 and 5-14 R3 OH O HO OH OH O O R3 OH 2Eq TFA R3=Br,NO2Compound 5-11 R3=Br Compound 5-12 R3=NO2H R=BrCompound 5-11 R=NO2Compound 5-12 R=BrCompound 5-13 R=NO2Compound 5-14 N OH HO OH NH2 H2N OH O HO OH +2Eq. H N HO OH HO

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131 Figure 5-23. Schematic diagram of th e structures of 5-15, 5-16, and 5-17. Figure 5-24. Crystal structure of 5-16; Co (II) is arranged in an octahedral geometry. N O HO Br OH N O OH Br HO M=Co(II)Compound 5-15 M=Zn(II)Compound 5-17 Compound 5-16 Co N O HO O2N OH N O OH NO2 HO M

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132 Figure 5-25. Catalytic reaction of the ethyl a ddition to benzaldehyde used as a standard to monitor the catalytic ab ility of the compounds O Et2Zn OH Catalyst

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133 LIST OF REFERENCES 1) Bianchi, E.; Bowman-James, K.; Garcia-Espana, E., Eds. Supramolecular Chemstry of Anions: Wiley-VCH: New York, 1997. 2) Sessler, J.; Gale, P.; Cho, W. Anion Receptor Chemistry : RSC Publishing : Cambridge, 2006. 3) Alberts, B.; Bray, D.; Lewis, M.; Raff, M.; Roberts, K.; Watson, J. Molecular Biology of the Cell 3rd edn, Garland Science, New York, 1994. 4) Anderson, M.; Gregory, R.; Thompson, P.; Souza, D.; Paul, S.; Mulligan, A.; Smith, A.; Welsh. Science 1991 253, 202. 5) Simon, D.; Bindra, R.; Mansfield, T.; Nelson-Williams, C.; Mendonca, E.; Stone, R.; Schurmann, S.; Nayir, A.; Alpay, H.; Bakkal oglu, A.; Rodriguez-Soriano, J.; Morales, J.; Sanjad, S.; Taylor, C.; Pilz, D.; Brem A.; Trachtman, H.; Griswold, W.; Richard, G.; Lifton, J. Nat. Genet. 1997 17, 171. 6) Devuyst, O.; Christie, P.; Courtoy, P.; Beauwens, R.; Thakker, R. Hum. Mol. Genet 1999 8, 247. 7) Scott, D.; Wang, R.; Kreman, T. ; Sheffield, V.; Karniski, L. Nat. Gen. 1999 21, 440. 8) Yoshida, A.; Taniguchi, S.; Hisotome, I.; R oyaux, I.; Green, E. ; Kohn, L. ; Suzuki, K. J. Clin. Endo. Metab. 2002 87, 3356. 9) For Examples: (a) Schmitdchen, F.; Berger, M. Chem. Rev 1997 97, 1609. (b) Antonisse, M.; Reinhoudt, D. Chem. Comm. 1998 443. (c) Martinez-Manez, R.; Sancenon, F. Chem. Rev. 2003 103, 4419. 10) For example: Woods, C.; Camiolo, S.; Light, M. E.; Coles, S. J.; Hursthouse, M. B.; King, M. A.; Gale, P.A.; Essex, J. W. J. Am. Chem. Soc. 2002 124 8644. 11) (a) Sessler, J. L.; Camiolo, S.; Gale, P.A. Coord. Chem. Rev. 2003 240 17. (b) Llinares, J. M.; Powell, D.; Bowman-James, K. Coord. Chem. Rev. 2003 240 57. (c) Bondy, C. R.; Loeb, S. J. Coord. Chem. Rev. 2003 240 77. (d) Choi, K.; Hamilton, A. D. Coord. Chem. Rev. 2003 240 101. (e) Lamber, T. N.; Smith B. D.; Coord. Chem. Rev. 2003 240 129. (f) Davis, A. P.; Joos, J.-B. Coord. Chem. Rev. 2003 240 143. 12) Lehn, J. Supramolecular Chemistry ; VCH Weinheim, 1995. 13) Lohr, H.; Vogtle, F. Acc. Chem. Res. 1985 18, 65. 14) Czarnik, M. Acc. Chem. Res. 1994 27, 302. 15) Bowman-James, K. Acc. Chem. Res. 2005 38, 671.

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134 16) For example: (a) Melaimi, M.; Gabbai, F. P. J. Am. Chem. Soc. 2005, 127, 9680. (b) Cottone, A.; Scott, M.J. Organometallics 2000 19, 5254. (c) Katz, H. J. Org. Chem. 1985 50, 5027. (d) Katz, H. J. Am. Chem. Soc. 1986 108, 7640. (e) Tamao, K.; Hayashi, T.; Ito, Y. J. Organomet. Chem. 1996 506, 85. (f) Williams, V.; Piers, W.; Clegg, W.; Elsegood, M.; Collins, S.; Marder, T. J. Am. Chem. Soc. 1999 121, 3244. (g) Sol, S.; Gabbai, F.P.; Chem Commun. 2004 11, 1284. (h) Chaniotakis, N.; Jurkschat, K.; Mller, D.; Perdikaki, K.; Reeske, G. Eur. J. Inorg. Chem. 2004 11, 2283. 17) For example: (a) Anzenbacher, P.; Jursikova, K.; Sessler, J. J. Am. Chem. Soc 2000 122 9350. (b) Woods, C.; Salvatore, C.; Light, M. E.; Coles, S. J.; Hursthouse, M. B.; King, M. A.; Gale, P.A. Essex, J. W. J. Am. Chem. Soc. 2002 124 8644. (c) Kang, S. O.; VanderVelde, D.; Powell, D.; Bowman-James, K. J. Am. Chem. Soc. 2004 126 12272. 18) Moyer, B.; Bonnesen, P. in Supramolecular Chemistry of Anions ed. A. Bianchi, K. Bowman-James, K. Garica-Espana and E. Garcia-Espana. Wiley-VCH, New York, 1997, pp.1-44. 19) Jeffrey, G. An Introduction o Hydrogen Bonding ; Oxford Universities Press: New York, 1997. 20) Desiraju, G. Acc. Chem. Res. 2002 35, 565. 21) Pauling, L. The Nature of the Chemical Bond Cornel University Press: Ithica, New York, 1939. 22) Kubik, S.; Reyheller, C.; Stuwe, S.; J. Incl. Phenom. Macroc. Chem. 2005 52, 137. 23) Park, C.; Simmins, H. J. Am. Chem. Soc. 1968 90, 2431. 24) Graf, E.; Lehn, J. J. Am. Chem. Soc. 1976 98, 6403. 25) Lehn, J.; Sonveaux, E.; Willard, A. J. Am. Chem. Soc. 1978 100, 4914. 26) Dietrich, B.; Lehn, J.; Guilhem, J.; Pascard, C. Tetrahedron Lett. 1989. 30, 4125. 27) Reilly, S.; Khalsa, D.; Ford, D.; Brainard, J.; Hay, B.; Smith, P. Inorg. Chem. 1995 34, 569. 28) Schmidtchen, F. Angew. Chem. Int. Ed. Engl. 1977 16, 720. 29) Worm, K.; Schmidtchen, F.; Schier, A.; Schafer, A.; Hesse, M. Angew. Chem. Int. Ed. 1994 33, 327. 30) Bauer, V.; Clive, D.; Dolphin, D.; Paine, J.; Harris. F.; King, M.; Loder, S.; Wang, W.; Woodward, R. J. Am. Chem. Soc. 1983 105, 6429. 31) Sessler, J.; Cyr, M.; Lync h, V.; McGhee, E.; Ibers, J. J. Am. Chem. Soc. 1990 112, 2810.

PAGE 135

135 32) Sessler, J.; Cyr, M.; Furuta, H.; Kral, V.; Mody, T.; Morishima, T.; Shionoya, M.; Weghorn, S. Pure Appl. Chem. 1993 65, 393. 33) Dietrich, B. Pure Appl. Chem. 1993 7, 1257. 34) Schmidtchen, F.; Tetrahedron Lett. 1989 30, 4493. 35) Valiyaveettil, S.; Engbersen, F.; Verboom, W.; Reinhoudt, D. Angew. Cehm. Intl. Ed. 1993 32, 900. 36) Gale, P. Coor. Chem Rev. 2003 240, 191. 37) Kang, S.; Llinares, J.; Powell, D.; VanderVelde, D.; Bowman-James, K. J. Am. Chem. Soc. 2003 125, 10152. 38) Katz, H. in Inclusion Compounds Atwood, J.; Davies, J.; MacNicol, D. Oxford University Press Publishers, Oxford, 1991 Vol 4, Chapter 9, pp. 391-405. 39) Rudkevik, D.; Verboom, W.; Reinhoudt, D. J. Org. Chem. 1994 59, 3683. 40) D. M. Rudkevich, W. Verboom, Z. Brzozka, M. J. Palys, W. P. R. V. Stauthhamer, G.J. van Hummel, S. M. Fraken, S. Harkema, J. F. J. Engbersen and D. N. Reinhoudt, J. Am. Chem. Soc. 1994. 116, 4341. 41) (a) White, D.; Laing, N.; Miller, H.; Parsons, S.; Coles, S.; Tasker, P. Chem. Commun. 1999 2077. (b) Miller, H.; Laing, N.; Pa rsons, S.; Parkin, A.; Tasker, P. J. Chem. Soc. Dalton Trans. 2000 3773. 42) (a) Vermersch, P.; Lemon, D.; Tesmer, G.; Quiocho, F. Biochemistry 1991 30, 6861. (b) Vyas, N.; Vyas, M.; Quiocho, F. Science 1988 242,1290. (c) Spurlino, J.; Lu, G.; Quiocho, F. J. Biol. Chem. 1991 266, 5202. 43) Smith, D. Org. Biol. Chem. 2003 1, 3874. 44) Zhou, G.; Cheng, Y.; Wang, L.; Jing, X.; Wang, F. Macromolecules 2005 38, 2148. 45) Dinger, M.; Scott, M. J. Eur. J. Org. Chem. 2000 2467. Dinger, M.; Scott, M. J. Chem. Commun. 1999 2525. 46) For example: (a) Turner, D. R.; Spencer, E. C.; Howard, J. A. K.; Tocher, D. A.; Steed, J. W. Chem. Commun 2004 1352. (b) Bondy, C. R.; Gale, P. A.; Loeb, S. J J. Am. Chem. Soc 2004 126, 5030. (c) Beer, P. D.; Hayes, E. J. Coord. Chem. Rev 2003 240, 167. 47) (a) Dutzler, R.; Campbell, E. B.; M acKinnon, R. Science 2003, 300, 108. (b) Dutzler, R.; Campbell, E. ; Cadene, M. ; Chait, B. ; MacKinnon, R. Nature, 2002, 415, 287.

PAGE 136

136 48) (a) Kolbe, M.; Besir, H.; Essen, L. O.; Oesterhelt, D. Science 2000, 288, 1390. (b) Facciotti, M. T.; Cheung, V. S.; Lunde, C. S.; Rouhani, S.; Baliga, N. S.; Glaeser, R. M. Biochemistry 2004, 43, 4934. 49) For a review of sulphate a nd phosphate binding sites see: Copl ey, R. R.; Barton, G. J.; J. Mol. Biol. 1994, 242, 321. 50) Channa, A.; Steed, J. W.; J. Chem. Soc. Dalton Trans. 2005, 2455. Ghosh, S.; Choudhury, A. R.; Row, T. N. G.; Maitra, U. Org. Lett. 2005, 7, 1441. Zhou, G.; Cheng, Y.; Wang, L.; Jing, X.; Wang, F. Macr omolecules, 2005, 38, 2148. Smith, D.; Org. Biomol. Chem. 2003, 1, 3874. Lee, K. H.; Lee, H. Y.; Lee, D. H.; Hong, J. I. Tetrahedron Lett. 2001, 42, 5447. 51) Kondo, S. I.; Suzuki, T.; Toyama, T.; Yano, Y. Bull. Chem. Soc. Jpn. 2005, 78, 1348. Hiratani, K.; Sakamoto, N.; Kameta, N.; Karikomia, M.; Nagawa, Y. Chem. Commun. 2004, 1474. Miyaji, H.; Sessler, J. L.; A ngew. Chem. Int. Ed. 2001, 40, 154. Jeong, K. S.; Hahn, K. M.; Cho, Y. L. Tetrahedron Lett. 1998, 39, 3779. Davis, A. P.; Gilmer, J. F.; Perry, J. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 1312. Beer, P. D.; Dent, S. W.; Wear, T. J. J. Chem. Soc. Dalton Trans. 1996, 2341. 52) Antonisse, M. M. G.; Reinhoudt, D. N. Chem Commun. 1998, 443. Plieger, P. G.; Tasker, P. A.; Galbraith, S. G. J. Chem. Soc. Dalton Trans. 2004, 313. 53) Cottone, A.; Morales, D.; Lecuivre, J. ; Scott, M. J. Organometallics. 2002, 21, 418. 54) de Castro, B.; Ferreira, R.; Freire, C.; Garcia, H.; Palomares, E. J. ; Sabater, M. J. New. J. Chem. 2002, 26, 405. 55) Shimazaki, Y.; Tani, F.; Fukui, K.; Naru ta, Y.; Yamauchi, O. J. Am. Chem. Soc. 2003, 125, 10512. 56) Kang, S.; Llinares, J.; Powell, D.; VanderV elde, D.; Bowman-James, K. J. Am. Chem. Soc. 2003, 125, 10152. 57) Shionoya, M.; Furuta, H.; Lynch, V.; Harriman, A.; Sessler, J. J. Am. Chem. Soc. 1992, 114, 5714. 58) Kang, S. O.; VanderVelde, D.; Powell, D.; Bowman-James, K. J. Am. Chem. Soc. 2004, 126, 12272. 59) Bourson, J.; Pouget, J.; Valeur, B.; J. Phys. Chem. 1993, 97 4552. 60) With help from Chase Rainwater on computer program 61) Lai, C.; Mak, W.; Chan, E.; Sau, Y.; Zh ang, Q.; Lo, S.; Williams, I.; Leung, W. Inorg. Chem. 2003, 42, 5863. 62) Zhou, X.; Huang, J.; Yu, X.; Zhou, Z.; Che, C. J. Chem. Soc. Dalton Trans. 2000, 7, 1075.

PAGE 137

137 63) Libra, E.; Scott, M. Chem Commun. 2006. 1485. 64) Campbell, E.; Nguyen, S. Tett. Lett. 2001. 42, 1221. 65) Synthesis developed by Melanie Veige 66) Etter, M.; Urbanczyk-Lipkowska, Z. ; Zia-Ebrahimi, M.; Pununto, T. J. Am. Chem. Soc. 1990 112, 8415. 67) Gale, P. Coor. Chem. Rev. 2003 240, 191. 68) Kelly, T.; Kim, M. J. Am. Chem. Soc. 1994 116, 7072. 69) Snellink-Ruel, B.; Antonisse, M.; Engberson, J.; Timmerman, P.; Reinhoudt, D. Eur. J. Org. Chem. 2000 165. 70) (a) Turner, D.; Pate rson, M.; Steed, J. J. Org. Chem. 2006 71(4), 1598. (b) Oh, J.; Cho, E.; Ryu, B.; Lee, Y.; Nam, K. Bull. Korean Chem. Soc. 2003 24, 10. 71) Bondy, C.; Gale, P.; Loeb, S. J. Am. Chem. Soc. 2004 126, 5030. 72) Bordwell, F. Acc. Chem. Res. 1988, 21, 456. 73) Nishizawa S.; Buhlmann P.; Iwao M.; Umezawa Y. Tetr. Lett. 1995 36, 6483. 74) Gomez, D.; Fabbrizzi, L.; Licchelli, M.; Monzani, E. Org. Biomol. Chem. 2005, 3, 1495. 75) Boiocchi, M.; Del Boca, L.; Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M.; Monzani, E. Chem. Eur. J. 2005 11, 3097. 76) Amendola, V.; Boiocchi, M.; Colasson, B.; Fabbrizzi, L. Inorg. Chem. 2006, 45(16), 6138. 77) Shimazaki, Y.; Tani, F.; Fukui, K.; Naruta, Y. ; Yamauchi, O. J. Am. Chem. Soc 2003 125, 10512. 78) Mizukami, S.; Houjou, H.; Kanesato, M.; Hiratani, M. Eur. J. Chem. 2003 9(7), 1521. 79) Cozzi, P. Chem Soc. Rev. 2004 33, 410. 80) Baleizao, C.; Garcia, H. Chem. Rev. 2006 106, 3987. 81) Jocabson, E.; Zhang, W.; Muci, A.; Ecker, A.; Deng, J. J. Am.Chem. Soc. 1991 113, 7063. 82) Schaus, S.; Branalt, J.; Jacobson, E. J. Org. Chem. 1998 63, 403.

PAGE 138

138 83) (a) Saito, B.; Katsuki, T. Tetrahedron Lett. 2001 42, 3873. (b) Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc 1993 115, 5326. (c) Martinez, L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N. J. Am. Chem. Soc. 1995 117, 5897. 84) Katsuki, T. Synlett. 2003 281. 85) Samsel, E.; Srinivasan, K. Kochi, J. J. Am. Chem. Soc. 1985 107, 7606. 86) Srinivasan, K.; Michaud, P.; Kochi, J. J. Am. Chem. Soc. 1986 108, 2309. 87) For example: Collin, J.; Da ran, J.; Schulza, E.; Trifonov, A. Chem. Commun. 2003 3048. 88) For exampls: Zhang, W.; Loeban, J.; Wilson, S.; Jacobson, E. J. Am. Chem. Soc. 1990 112(7), 2801. 89) Fukuda, T.; Irie, R.; Katsuki, T. Synlett 1995 197. 90) Yamamoto, H.; Susumu, S. Pure & Appl. Chem. 1999 71(2) 239. 91) Corey, E.; Huzman-Perez, A. Angew. Chem. Int. Ed. 1998 37, 388. 92) Dias, L. Current Org. Chem. 2000 4, 305. 93.) Cozzi, P. ; Papa, A. ; Umani-Ronchi, A. Tett. Lett. 1996 37(26), 4613. 94) DiMauro, E. ; Kozlowski, M. Org. Lett. 2001 3(19), 3053. 95) (a) Garcia, C. ; LaRochelle, L.; Walsh, P. J. Am. Chem. Soc. 2002 124, 10970. (b) DiMauro, E.; Kozlowski, M. J. Am. Chem. Soc. 2002 124, 12668. 96) Cozzi, P. Angew. Chem. Int. Ed. 2003 42, 2895. 97) Corey, E. Angew. Chem. Int. Ed. 2002 41, 1650. 98) Ahrendt, K.; Borths, C.; MacMillan, D. J. Am. Chem. Soc. 2000 122, 4243. 99) Chapman, J.; Day, C.; Welker, M. Organometallics 2000 19(9), 1615. 100) Takenaka, N.; Huang, Y.; Rawal, V. Tetrahedron 2002 58, 8299. 101) Yamamoto, H.; Futatsugi, K. Angew. Che. Intl. Ed. 2005, 44, 1924. 102) Chang, K.; Huang, C.; Liu, Y.; Hu, Y.; Chou, P.; Lin, Y. Dalton Trans. 2004 1731. 103) (a) Morris, G.; Zhou, H. ; Stern, C.; Nguyen, S. Inorg. Chem. 2001, 40, 3222. (b) Korupoju, S.; Mangayarkarasi, N.; Ameerunish a, S.; Valente, E.; Zacharias, P. Dalton Trans 2000 2845. (c) Szlyk, E.; Wojtczak, A.; Su rdykowski, A.; Gozdzikiewicz, M. Inorg Chem Acta 2005 358, 467.

PAGE 139

139 104) (a) Gao, J.; Reibenspies, J. H.; Zingaro, R. A.; Woolley, F. R.; Martell, A. E.; Clearfield, A. Inorg. Chem 2005 44(2), 232. (b) Huang, W.; Gou, S.; Hu, D.; Chantrapromma, S.; Fun, H.-K.; Meng, Q. Inorg. Chem 2001 40(7), 1712. 105) Chen, G.; Zhai, B.; Sun, M.; Qi, W.; Acta Crystallogr. E. 2005 61, m1869. 106) Wiznycia, A.; Desper, J.; Levy, C.; Chem. Commun 2005 37,4693. 107) Bunge, J.; Boyle, T.; Pratt, H.; Alam, T.; Rodriguex, M. Inorg. Chem. 2004 6035. 108) (a) Bunge, S. D.; Boyle, T. J.; Pratt, H. D., III; Alam, T. M.; Rodriguez, M. A. Inorg. Chem 2004 43(19); 6035. (b) Chisolm, M.; Huang, J.; Huffman, T.; Streib, W.; Tiedtke, D. Polyhedron 1997 16, 2941. 109) (a) Gambarotta, S.; Arena, F. ; Floriani, C.; Zanazzi, P. J. Am. Chem. Soc. 2000 122, 8946. (b) Schaus, S.; Brandes, B.; Larrow, J.; Tokunaga, M.; Hansen, K.; Gould, A.; Furrow, M.; Jacobsen, E. J. Am. Chem. Soc. 2002 124, 1307. 110) Uchida, T.; Katuski, T.; Ito, K.; Akashi, S.; Kuroda, T. Helvetica Chimica Acta 2002 85, 3078. 111) Shen, Y.-M.; Duan, W.-L.; Shi, M. J. Org. Chem 2003 68(4), 1559. 112) Lindoy, L.; Meehan, G.; Svenstrup, N. Synthesis 1998 7, 1029.

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140 BIOGRAPHICAL SKETCH Eric Libra was born in Erie, Pennsylvania in 198 0. His love for scien ce began at an early age and an interest in chemistry began wh ile at General McLane High school, where he graduated as valedictorian in 1998. He earned a B.S. in chemistry from Boston College in 2002 where he worked in Professor William Armstrong s research group, which was his first exposure to inorganic chemistry. Eric began his graduate studies at the Univer sity of Florida in 2003 where he joined Professor Michael Scotts group. Upon completion of his Ph.D, Eric will join Adesis Inc. in New Castle, Delaware as a synthetic chemist.