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Anion Binding and Catalytic Studies of Metal Salen Complexes

Permanent Link: http://ufdc.ufl.edu/UFE0024865/00001

Material Information

Title: Anion Binding and Catalytic Studies of Metal Salen Complexes
Physical Description: 1 online resource (158 p.)
Language: english
Creator: Zieleniuk, Candace
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2009

Subjects

Subjects / Keywords: anion, binding, catalysis, metal, salens, triphenoxymethane
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: Of all the substrates and cofactors involved in biological processes, it is estimated that 70-75% of the species are negatively charged. Since anionic species are essential for life, their presence or imperfect regulation can be either beneficial or harmful to living organisms. Despite the importance of anions in nature, the recognition of anions by synthetic hosts has been largely unexplored. A series of tripodal triphenoxymethane salens were synthesized and then used to chelate lanthanides and transition metals with 3+oxidation states. The metal chelation facilitates the formation of well-defined binding pockets containing six O-H moieties of varying sizes depending upon the chelated metal ion. The same approach was also used to produce large macrocyclic urea-based salen ligands and the corresponding metal complexes as well as mixed O-H/N-H metal salens. Both the O-H and N-H based complexes were treated with the tetrabutylammonium salts of a wide range of anion and then studied for their anion binding capabilities. Chiral metal salen molecules have also been used extensively to perform asymmetric catalysis. A series of chiral BINAM triphenoxymethane based salen ligands were produced and used to synthesize extremely bulky chiral dinuclear catalysts. These catalysts were found to facilitate the asymmetric addition of ZnEt2 to benzaldehyde giving a secondary alcohol. In addition, the chiral BINAM catalysts can also produce quantitative amounts of cyclic carbonates through a cycloaddition reaction of CO2 to epoxides. The synthesis of the metal salen complexes and the results of the anion binding and catalytic studies are presented herein.
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 Candace Zieleniuk.
Thesis: Thesis (Ph.D.)--University of Florida, 2009.
Local: Adviser: Scott, Michael J.
Electronic Access: RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2010-02-28

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2009
System ID: UFE0024865:00001

Permanent Link: http://ufdc.ufl.edu/UFE0024865/00001

Material Information

Title: Anion Binding and Catalytic Studies of Metal Salen Complexes
Physical Description: 1 online resource (158 p.)
Language: english
Creator: Zieleniuk, Candace
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2009

Subjects

Subjects / Keywords: anion, binding, catalysis, metal, salens, triphenoxymethane
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: Of all the substrates and cofactors involved in biological processes, it is estimated that 70-75% of the species are negatively charged. Since anionic species are essential for life, their presence or imperfect regulation can be either beneficial or harmful to living organisms. Despite the importance of anions in nature, the recognition of anions by synthetic hosts has been largely unexplored. A series of tripodal triphenoxymethane salens were synthesized and then used to chelate lanthanides and transition metals with 3+oxidation states. The metal chelation facilitates the formation of well-defined binding pockets containing six O-H moieties of varying sizes depending upon the chelated metal ion. The same approach was also used to produce large macrocyclic urea-based salen ligands and the corresponding metal complexes as well as mixed O-H/N-H metal salens. Both the O-H and N-H based complexes were treated with the tetrabutylammonium salts of a wide range of anion and then studied for their anion binding capabilities. Chiral metal salen molecules have also been used extensively to perform asymmetric catalysis. A series of chiral BINAM triphenoxymethane based salen ligands were produced and used to synthesize extremely bulky chiral dinuclear catalysts. These catalysts were found to facilitate the asymmetric addition of ZnEt2 to benzaldehyde giving a secondary alcohol. In addition, the chiral BINAM catalysts can also produce quantitative amounts of cyclic carbonates through a cycloaddition reaction of CO2 to epoxides. The synthesis of the metal salen complexes and the results of the anion binding and catalytic studies are presented herein.
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 Candace Zieleniuk.
Thesis: Thesis (Ph.D.)--University of Florida, 2009.
Local: Adviser: Scott, Michael J.
Electronic Access: RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2010-02-28

Record Information

Source Institution: UFRGP
Rights Management: Applicable rights reserved.
Classification: lcc - LD1780 2009
System ID: UFE0024865:00001


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1 ANION BINDING AND CATALY TIC STUDIES OF METAL SALEN COMPLEXES By CANDACE A. ZIELENIUK 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 2009

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2 2009 Candace A. Zieleniuk

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3 To Chase, my Mom, and my family

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4 ACKNOWLEDGMENTS I cannot begin to voice the amount of gratitude that I have for my mother, Karla Rainwater. She has been an inspiration to me si nce I was a little girl. I learned first-hand from her about hard work, dedication, a nd perseverance. She always believed in me and never let me forget it. I want to thank her for patiently listening to me as I freaked out about missing a question on a test or when I t hought I had gotten a B in a clas s, for cheering me on when I thought I could not do it anymore, and loving me so much that I knew things would be fine whether I succeeded or failed. Without her I would not be where I am today. I would also like to thank the teachers and professors who inspired me to become a chemist and pursue a graduate degree. First, I want to thank my high school chemistry teacher, Mr. Smith. He was an amazing teacher and it was in his class that I first fell in love with chemistry. Dr. Neil Allison at the University of Ar kansas, he gave me the opportunity to work as a synthetic chemist for the first time in his lab group. He was the person who finally convinced me that I had a talent for chemistry and should co ntinue my studies by going to graduate school. Next, I would like to thank Dr. Michael Scott for choosing me as his REU student in the summer of 2002. Without him I wo uld have never discovered my love for inorganic chemistry or attended the University of Florida. He has been a patient and understanding advisor who allowed me the freedom to work in the lab and le arn from my mistakes. I am a better synthetic chemist because of him. I must also thank Dr. Ben Smith for choosing me to represent the Chemistry department for a chance to win a Disse rtation Fellowship and the College of Liberal Arts and Sciences for choosing me as one of the recipients of the award. The student-free semester this fellowship granted me was instrume ntal in helping me fini sh this body of work. Finally, I would like to thank Dr. Khalil Abboud for his advice and his gracious assistance on multiple occasions.

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5 There were many people who made life in the la b as well as life out of the lab enjoyable for me the past six years. First, I would lik e to thank Scott group members Hu, Ivana, Nela, Ranjan, Ozge, Patrick, Gary, Anna, Dempsey, and Nate, who taught me so many things over the years and were always here to discuss ideas and stra tegies. I want to especi ally thank Eric Libra, adopted Scott group member Justin Gardner, and Monique Williams. We were together through classes, cumes, orals, and the ups and downs th at come with research. They always had a sympathetic ear as well as encouraging words. Th ey made this process more fun, and I will never forget their friendship. I also must thank Matt Jeletic, who taught me almost everything I know about catalysis. Next, I woul d like to thank James Leonard, Emily Rasch, and the Saturday football crew. I have so ma ny fond memories of those amazing Saturday afternoons and evenings. Last and certainly not least, I want to thank my husband, Chase. I would have never thought when he asked me out in our 8th grade history class that we would be here today. I want to thank him for his patience, support, encouragement, and the academic competition over the years. Most of all, I need to thank him for comi ng to the University of Florida with me. I would not have survived the past six years without him.

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6 TABLE OF CONTENTS page ACKNOWLEDGMENTS ............................................................................................................... 4LIST OF TABLES .........................................................................................................................10LIST OF FIGURES .......................................................................................................................11ABSTRACT ...................................................................................................................... .............16 CHAP TER 1 INTRODUCTION .................................................................................................................. 18Polyamine Receptors ....................................................................................................... 19Guanidinium Receptors ...................................................................................................21Polypyrrolic Receptors ...................................................................................................21Neutral and Lewis Acidic Receptors ............................................................................... 22OH Based Receptors ........................................................................................................23Research Objectives ........................................................................................................ 242 ANION BINDING STUDIES WITH TRIPODAL METAL SALENS INCORPORATING TRIPHENOXYMETHANES ...............................................................30Introduction .................................................................................................................. ...........30Results and Discussion ........................................................................................................ ...33Triphenoxymethane Salens with Tren ............................................................................. 33Metallation of Tren Triphe noxymethane Salen 2-4a ....................................................... 34Metallation of Tren Trip henoxymethane Salen 2-4b ...................................................... 37Anion Binding Studies of 2-4a-La(III)CH3CN, 2-4a-Eu(III) CH3CN and 2-4aLa(III)THF .................................................................................................................. 39Triphenoxymethane Salens with Tame ........................................................................... 41Metallation of Tame Triphenoxymethane Salen 2-5b ..................................................... 42Anion Binding Studies of 2-5bCo(III) and 2-5b-Fe(III) ................................................44Twist Angles of Pseudo-Helical Lantha nide and Transition Metal Complexes ............. 47Conclusions .............................................................................................................................49Experimental .................................................................................................................. .........50General Considerations ...................................................................................................50General Procedure for the S ynthesis of Co mpounds 2-3 ................................................ 50Compound 2-3b ............................................................................................................... 50General Procedure for the S ynthesis of Co mpounds 2-4 ................................................ 51Compound 2-4a ............................................................................................................... 51Compound 2-4b ............................................................................................................... 51General Procedure for the Synthe sis of Compound 2-4a-M(III) ..................................... 52Compound 2-4a-La(III)CH3CN ..................................................................................... 52Compound 2-4a-La(III)THF .......................................................................................... 52

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7 Compound 2-4a-Eu(III)CH3CN ..................................................................................... 53Synthesis of 2-4b*-La(III) ................................................................................................ 53General Procedure for the S ynthesis of Co mpounds 2-5 ................................................ 54Compound 2-5a ............................................................................................................... 54Compound 2-5b ............................................................................................................... 54Synthesis of 2-5b-Co(III) ................................................................................................ 55Synthesis of 2-5b-Fe(III) .................................................................................................553 ANION BINDING STUDIES WITH METAL SALEN COMPLEXES INCORPORATING UREA MOIETIES ................................................................................ 71Introduction .................................................................................................................. ...........71Results and Discussion ........................................................................................................ ...74Reactions with Urea Aldehyde 3-10 ................................................................................ 74Anion Binding Studies of 3-13-La(III) ............................................................................76Reactions with Urea Dialdehyde 3-14 ............................................................................. 77Reactions of 3-14 with diamines .............................................................................. 77Anion binding studies with urea-based macrocycles 3-15a/b/c ............................... 78Metallation of macrocycles 3-15a/b/c ...................................................................... 78Reactions of (3-15a-Zn(II))2 with bipyridine ligands .............................................. 81Reactions of 3-14 with Tris-Amines ............................................................................... 82Conclusions .............................................................................................................................86Experimental .................................................................................................................. .........86General Considerations ...................................................................................................86Synthesis of 3-13-La(III) ................................................................................................. 87General Procedure for the Synt hesis of Compounds 3-15 .............................................. 87Compound 3-15a ............................................................................................................. 87Compound 3-15b ............................................................................................................. 88Compound 3-15c ............................................................................................................. 88General Procedure for the Synthe sis of Compounds (3-15-Zn(II))2 ...............................88Compound (3-15a-Zn(II))2 ..............................................................................................88Compound (3-15b-Zn(II))2 ..............................................................................................89Compound (3-15c-Zn(II))2 ..............................................................................................89Synthesis of 3-15a-Zn(II) py ..........................................................................................90Synthesis of 3-20 ............................................................................................................. 904 CHIRAL METAL SALENS INCORPORATING TRIPHENOXYMETHANES FOR CATALYSI S ..................................................................................................................... ...107Introduction .................................................................................................................. .........107The Addition of Et2Zn to Aldehydes by Chiral Metal Salen Complexes ...................... 109The Cycloaddition of Carbon Dioxide to Epoxides with Metal Salen Catalysts .......... 110General Approach for Producing New Chiral Metal Salen Complexes for Catalysis ..111Results and Discussion ........................................................................................................ .114Synthesis of Chiral and Racemic Dinuclear BINAM Catalysts .................................... 114The Addition of Et2Zn to Benzaldehyde with 4-7c/d-M(II) and 4-7c/d-M(II)/Ti(IV) .. 115

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8 The Cycloaddition of Carbon Dioxide to Epoxides with Mononuclear and Dinuclear BINAM Catalysts ...................................................................................... 116Attempts to Produce Additional Bulky Metal Salen Catalysts ..................................... 118Studies with Bulky Metal Salen 2-4a-La(III) CH3CN .................................................. 121Conclusions ...........................................................................................................................123Experimental .................................................................................................................. .......123General Considerations .................................................................................................123General Procedure for the S ynthesis of Co mpounds 4-6 .............................................. 124Compound 4-6e ............................................................................................................. 125Compound 4-6f .............................................................................................................. 125Compound 4-6g ............................................................................................................. 125Compound 4-6h ............................................................................................................. 126General Procedure for the S ynthesis of Chiral Compounds 4-7c/d-M(II/IV)/Ti(IV) ... 126Chiral Compound 4-7c-Co(II)/Ti(IV) ........................................................................... 126Chiral Compound 4-7c-Zn(II)/Ti(IV) ............................................................................ 127Chiral Compound 4-7d-Co(II)/Ti(IV) ...........................................................................127Chiral Compound 4-7d-Ti(IV)/Ti(IV) ...........................................................................127General Procedure for the Synthesi s of Racemic Compounds 4-7c/d .......................... 128Racemic Compound 4-7c .............................................................................................. 128Racemic Compound 4-7d .............................................................................................. 129Racemic Compound 4-7c-Co(II) ...................................................................................129Racemic compound 4-7d-Co(II) ....................................................................................129Racemic Compound 4-7c-Zn(II) ................................................................................... 130Racemic Compound 4-7d-Zn(II) ...................................................................................130General Procedure for the Synthesis of Racemic Com pounds 4-7c/d-M(II)/Ti(IV) ..... 131Racemic Compound 4-7c-Co(II)/Ti(IV) .......................................................................131Racemic Compound 4-7c-Zn(II)/Ti(IV) ........................................................................ 131Racemic Compound 4-7d-Co(II)/Ti(IV) ....................................................................... 132Racemic Compound 4-7d-Zn(II)/Ti(IV) .......................................................................132General Procedure for the Addition of Et2Zn to Benzaldehyde .................................... 132General Procedure for the Cycloadditi on of Epoxides with Carbon Dioxide ...............133General Procedure for the S ynthesis of Co mpounds 4-8 .............................................. 133Compound 4-8a ............................................................................................................. 133Compound 4-8b ............................................................................................................. 134Compound 4-8c ............................................................................................................. 134Compound 4-8d ............................................................................................................. 135General Procedure for the Synthe sis of Compounds 4-8-M(II) .................................... 135Compound (4-8a-Co(II))2 ..............................................................................................135Compound (4-8a-Fe(II))2 ...............................................................................................135Compound (4-8b-Zn(II))2 ..............................................................................................136Compound (4-8b-Co(II))2 ..............................................................................................136General Procedure for the S ynthesis of Co mpounds 4-9 .............................................. 136Compound 4-9a ............................................................................................................. 137Compound 4-9b ............................................................................................................. 137Compound 4-9f .............................................................................................................. 137Synthesis of Compound 4-9f-Co(II) ..............................................................................138

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9 General Procedure for the Synt hesis of Compounds 4-10 ............................................ 138Compound 4-10e ........................................................................................................... 138Compound 4-10f ............................................................................................................ 139Compound 4-10g ........................................................................................................... 139Compound 4-10h ........................................................................................................... 139LIST OF REFERENCES .............................................................................................................150BIOGRAPHICAL SKETCH .......................................................................................................157

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10 LIST OF TABLES Table page 2-1 Distances ( di) between planes (Fi) and the twist angles ( wi) in each portion. .................... 692-2 Crystallographic data fo r compounds 2-4a-La(III)CH3CN, 2-4a-La(III)THF, 2-4aEu(III)CH3CN, and 2-4b*-La(III). .................................................................................... 692-3 Crystallographic data for compounds 2-5b, 2-5b-Co(III), 2-5b-Fe(III), and 2-5bCo(III)-H2O. ....................................................................................................................... 703-1 Crystallographic data for com pounds 3-13-La(III), (3-15a-Zn(II))2, 3-15a-Zn(II)py, and 3-20. ..........................................................................................................................1064-1 CO2 coupling reactions with racemic propyl ene oxide and chir al catalyst 4-3. .............. 1474-2 Asymmetric addition of ZnEt2 to Benzaldehyde in 96 hours. ......................................... 1484-3 The effect of co-catalyst, temperatur e, and time on the formation of propylene carbonate from propylene oxide and CO2 at 500 psi. ......................................................1484-4 The cycloaddition of CO2 and various epoxides with 4-7d-Co(II)/Ti(IV) and 4-7dCo(II) at 500 psi. .............................................................................................................. 1484-5 The cycloaddition of CO2 and Propylene oxide with 4-7d-Zn(II)/Ti(IV) and 4-7dTi(IV)/Ti(IV) at 500 psi. ..................................................................................................1484-6 Crystallographic data for compound 4-7c-Co(II)/Ti(IV). ................................................ 149

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11 LIST OF FIGURES Figure page 1-1 Illustration of the encapsulation of a ha lide ion by the diammonium katapinands. .......... 251-2 Depiction of a hexaprotonated bis -tren polyamine-based cryptate. ...................................251-3 Examples of polyammonium macrom onocycles, which allow many positively charged nitrogen centers to exist is close proximity of one another. ................................. 251-4 Depiction of a polyammonium marcotricycl ic receptor. The additional macrocycles increases the rigidity and se lectively of the complex. ....................................................... 261-5 Representation of cyclophane receptors. Rigid aromatic spacers were used to increase the size of the receptor while restricting flexibility. ............................................ 261-6 Illustration of the bidentate ionic hydrogen bonds in a guanidinium salt. .........................261-7 Illustration of bis-bicyclic guanidinium receptor generated by linking two bicyclic guanidinium groups with a rigid spacer. ............................................................................271-8 Illustration of olgiopyrrole-derived recep tors. The original porphyrin macrocycle must be expanded to accommodate sm all anions such as fluoride. ................................... 271-9 Depiction of prodigiosin 1-14. The deri vative is part of a family of naturally occurring tripyrrolic red pigments isolated for the microorganisms Serratia and Streptomyces .....................................................................................................................271-10 Depiction of synthetic linear polypyrrolic prodigiosin derivatives. The binding affinity can be tuned by changing the groups of the pyrrole ring. ..................................... 281-11 Depiction of neutral Lewis acid receptor s, which use only Lewis acidic interactions to bind anions. ....................................................................................................................281-12 Illustration of a bifunctional receptor w ith a salen handle. The receptor can bind metal ions as well as anionic species. ................................................................................ 281-13 Representation of the large OH based r eceptors produced from monomers containing simple alcohol subunits. .....................................................................................................291-14 Depiction of the tripheno xymethane platform (1-23) in the all up c onfiguration. The platforms can be tethered to one a nother through a salen backbone and used to chelate metal ions to form select ive anion receptors 1-24a and 1-24b. ............................. 292-1 Schematic drawing of the residues in the ClC chloride channels of E. coli that are involved in the binding of a chloride anion. ...................................................................... 56

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12 2-2 Schematic drawing of the general synthesi s of the Schiff base ligand and Schiff base m etal complexes. (i) refluxing absolute ethanol, 24 hours; (ii) refluxing toluene, 24 hours. ........................................................................................................................ ..........562-3 Illustration of the synthe tic route used to prepare th e aldehyde derivative of the triphenoxymethane platform with different al kyl substituents at the 3 and 5 positions. ... 572-4 Illustration of the triphenoxymethane platform in the all up conformation. .................. 572-5 Illustration of Schiff ba se reaction of Tren with aldehyde derivative of the triphenoxymethane platform. (i) re fluxing absolute ethanol, 12 hours. ........................... 582-6 Illustration of the synthe tic route used to produce 24a-M(III). (i) La(III)(CF3SO3)3 or Eu(III)(CF3SO3)3, boiling acetonitrile, 5 minutes. .........................................................582-7 Solid-state structure of 2-4a-La(III) CH3CN with a coordinate d acetonitrile on the La(III) metal center (30% probability; carbon at oms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. ...................................................................... 592-8 Solid-state structure of 2-4a-La(III) THF with a coordinated THF on the La(III) metal center (30% probability; carbon atom s depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. ............................................................................. 592-9 Diagram of the solid-state structure of 2-4a-Eu(III) CH3CN with a coordinated acetonitrile on the Eu(III) metal center (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. ........................................... 602-10 Depiction of an additional synthe tic route used to produce 2-4-La(III). ........................... 602-11 Diagram of the solid state structure of ligand 2-4b*-La(III) (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. .......... 612-12 Schematic diagram of the proposed binding of perchlor ate to 2-4a-M(III). For clarity the diagram depicts one third of the metal complex and perchlorate anion. The t butyl groups and the hydrogen atoms are also omitted for clarity. .................................... 612-13 Depiction of the 1H NMR spectrum of 2-4-La(III)CH3CN (top) and the 1H NMR spectrum of 2-4-La(III)CH3CN treated with less th an one equivalent of tetrabutylammonium fluoride (bottom) in CDCl3..............................................................622-14 Synthetic scheme for the formation of triphenoxymethane salens 2-5a and 2-5b. (i) refluxing absolute ethanol, 12 hours. ................................................................................. 632-15 The solid-state structure of ligand 2-5b (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. ............................................ 63

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13 2-16 Synthetic scheme for the formation of 2-5b-Co(III) ((i) Co(II)acetate tetrahydrate, 5% H2O2, 70 C, THF/ethyl acetate, 5 minutes) and 2-5-Fe(III) ((i) Fe(III) perchlorate, CH3CN3/CHCl3, 15 minutes). ........................................................................642-17 The solid-state structure of complex 2-5b-Co(III). The hydrogen atoms are omitted for clarity (30% probability; carbon atom s depicted with arbitrary radii). ........................652-18 Diagram of the solid-state structure of ligand 2-5b-Fe(III) (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. ........... 662-19 Diagram of the solid-state structure of ligand 2-5b-Co(III)-H2O with water bound in the phenolic pocket (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. ...................................................................... 672-20 The simplified structure around the centra l metal ion of 2-4a-M(III). The atoms remote from the central metal ion as well as the hydrogen atoms were omitted for clarity. ................................................................................................................................672-21 The simplified structure around the centra l metal ion of 2-5b-M(III). The atoms remote from the central metal ion as well as the hydrogen atoms were omitted for clarity. ................................................................................................................................683-1 Depiction of the interaction be tween a urea-containing receptor and N, N -dimethylp-nitroaniline. ................................................................................................................ .....913-2 Illustration of m -phenyl spaced bis-urea (3-1) and o-phenylenediamine-based (3-2) receptors. .................................................................................................................... ........913-3 Depiction of two urea receptors with tris-amine spacers. .................................................. 913-4 Illustration of two cyclic urea-based anion receptors. ....................................................... 923-5 Illustration of a urea based receptor that is templated by a Pt(II) metal center. ................ 923-6 Illustration of urea-based colori metric sensors for anion binding. .................................... 923-8 Illustration of the synthetic scheme used to produce urea salen 3-11. ............................... 933-9 Schematic drawing of a bifunctional an ion receptor. The coordination of the chloride with two O-H and two N-H donors is similar to the binding of chloride in the ClC chloride channels found in E. coli. ....................................................................... 943-10 Schematic drawing of the synthesis of the mixed metal salen 3-13-La(III). (i) ethanol, triethylamine, and heat. ........................................................................................ 943-11 Depiction of the solid-state structure of 3-13-La(III). The hydrogen atoms are omitted for clarity. .......................................................................................................... ...953-12 Synthetic scheme for urea dialdehyde 3-14. ...................................................................... 96

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14 3-13 Depiction of the synthesis of urea-based m acrocycles 3-15a/b/c. ..................................... 963-14 Schematic drawing of the supramolecular box (3-16)2. ..................................................... 973-15 Depiction of the 1H NMR spectrum of 3-15b-Zn(II) in CD2Cl2. ....................................... 973-16 Illustration of the synthetic rout e used to produced (3-15a/b/c-Zn(II))2. (i) Zn(II) Acetate, refluxing THF, trie thylamine, 12 hours. The c oordinated THF molecules on Zn1 and Zn2 were omitted for clarity. ................................................................................ 983-17 Solid-state structure of (3-15a-Zn(II))2 (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. ........................................... 993-18 Solid-state structure of 3-15a-Zn(II) py (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. .................................. 1003-19 Schematic representation of the interact ions in the solid produced when (3-15aZn(II))2 is treated with 1,2-bi s(4-pyridyl)ethylene. ......................................................... 1013-20 Schematic representation of the interact ions in the solid produced when (3-15aZn(II))2 is treated with 4-4-bipyridine. ........................................................................... 1023-21 Schematic drawing of the metal template synthesis of dinucl ear lanthanide(III) and yttrium(III) cryptates. (i) trieth ylamine, methanol, 30 minutes. ..................................... 1033-22 Illustration of the tris -amines Tame (left) and Tach (right). ............................................1033-23 Depiction of the tris -amine 3-19. .....................................................................................1033-24 Illustration of the synthetic route to produce cryptate 3-20. (i) ethanol, reflux, 24 hours. ........................................................................................................................ ........1043-25 The solid-state stru cture of cryptate 3-20 (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. .................................. 1053-26 Illustration of 1O -octyl-D-glucopyranoside (left) and 1O -octyl-Dglucopyranoside (right). ...................................................................................................1054-1 Illustration of the metal salen co mplex known as Jacobsens catalyst. ........................... 1404-2 Illustration of the enan tioselective addition of Et2Zn to benzealdehyde. The chiral Schiff base Zn(II) complex is produced in situ ............................................................... 1404-3 Illustration of the axially ch iral Schiff base ligand used to make bimetallic catalysts. ... 1404-4 Depiction of two pathways envisioned for the formation of chiral carbonates via intramolecular cyclic elimination. ................................................................................... 141

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15 4-5 Illustration of the general scheme for the en antiospecific addi tion of carbon dioxide to an epoxide. ...................................................................................................................1414-6 Illustration of BINAD Co(III) complexes used for the asymmetric cycloaddition of carbon dioxide with epoxides. ......................................................................................... 1424-7 Solid-state structure of a chiral Ni(II)-triphenoxymethane salen made with R,R -1,2diaminocyclohexane. ....................................................................................................... 1424-8 Illustration of the synthetic scheme used to make the four derivatives of the BINAM triphenoxymethane salens. (i ) ethanol, reflux, 24 hours. ................................................ 1434-9 Solid-state structure of binuclear BINAM salen 4-7a-Zn(II)/Ti(IV). .............................. 1434-10 Synthetic scheme for the production of the chiral dinuclear catalysts 4-7c/dM(II)/Ti(IV). (i) Titanium isopropoxide, inert atmosphere, 12 hours. ...........................1444.11 The solid-state structure of 4-7c-Co(II)/Ti(IV) (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. .................... 1444-12 Illustration of the synthetic scheme used to make the triphenoxymethane salens with (-)-(R,R )-11,12-Diamino-9,10-dihydro -9,10-ethanoanthracene (i) ethanol, reflux, 24 hours. ...........................................................................................................................1454-13 Depiction of the synthetic scheme used to make the triphenoxymethane salens with meso -1,2-Diphenylethylenediamine. (i) ethanol, reflux, 24 hours. ................................ 1454-14. Illustration of the synthetic ro ute used to produced (4-8a/b-M(II))2. (i) M(II) Acetate, refluxing methanol, the time varied between 10 minutes and 24 hours. .........................1464-15 Illustration of bulky designer Lewis acid catalysts used in selective carbon-carbon bond-forming reactions. ...................................................................................................1464-16. Illustration of Schiff base reaction used to produce Tren triphenoxymethane salens. (i) refluxing absolute ethanol, 12 hours. ............................................................................... 147

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16 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 ANION BINDING AND CATALY TIC STUDIES OF METAL SALEN COMPLEXES By Candace A. Zieleniuk August 2009 Chair: Michael J. Scott Major: Chemistry Of all the substrates and cof actors involved in biological proc esses, it is estimated that 7075% of the species are negatively charged. Sinc e anionic species are essential for life, their presence or imperfect regulation can be either beneficial or harm ful to living organisms. Despite the importance of anions in nature, the recognition of anions by synthetic hosts has been largely unexplored. A series of tripoda l triphenoxymethane salens were synthesized and then used to chelate lanthanides and transition metals with 3+oxidation states. The metal chelation facilitates the formation of well-defined binding pockets containing six O-H moieties of varying sizes depending upon the chelated metal ion. The same approach was also used to produce large macrocyclic urea-based salen ligands and the corresponding metal complexes as well as mixed O-H/N-H metal salens. Both the O-H and N-H based complexes were treated with the tetrabutylammonium salts of a wide range of anion and then studied for their anion binding capabilities. Chiral metal salen molecules have also been used extensively to perform asymmetric catalysis. A series of chiral BINAM triphenoxym ethane-based salen ligands were produced and used to synthesize extremely bulky chiral dinucl ear catalysts. These catalysts were found to facilitate the asymmetric addition of ZnEt2 to benzaldehyde giving a secondary alcohol. In

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17 addition, the chiral BINAM catalysts can also produce quantitative amounts of cyclic carbonates through a cycloaddition reaction of CO2 to epoxides. The synthesis of the metal salen complexes and the results of the anion binding and cat alytic studies are presented herein.

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18 CHAPTER 1 INTRODUCTION The importance of anions in biological system s as well as in the natural world as a whole has been grossly overlooked. Of all the subs trates and cofactors i nvolved in biological processes, from gene replica tion to energy transduction, 70-75% of the sp ecies are negatively charged.1-2 Since anionic species are essential for life, their presence or imperfect regulation can be either beneficial or harmful to living orga nisms. For example, phosphate bearing nucleotide analogues display antiviral activity against herp es simplex and AIDS, but the imbalance of chloride has been pinpointed as the cause for mucous deposits in the lungs, which is a symptom of cystic fibrosis.3-6 Additionally, anions found in soil, food, and water, such as sulfates, nitrates, sulfides, thiosulfides, cyanides, and heavy-meta l based anions, present a health risk to the population at large.7 Therefore, it is in the interest of the general public to have selective synthetic anion receptors that can be used to regulate anions for a wide variety of purposes. Despite the importance of anions in nature the recognition of ani ons by synthetic hosts has been largely underexplored compared to th e large number of synthetic cationic receptors present in the literature. The di screpancy is largely because the coordination of anions is more challenging than the coordination of cations for se veral reasons. 1) Cations tend to be smaller and spherical, while anions ar e larger and exist in numerous geometric forms: spherical (F-, Cl-, Br-), tetrahedral (PO4 3-, SO4 2-), planar (NO3 -), and linear (SCN-, N3 -). 2) Anions have higher solvation energies than cations of a similar size. Thus, a synthetic anion receptor must be more competitive than a synthetic cation receptor in the same solvent. 3) Anions are usually saturated with respect to their coordination; as a resu lt, receptor molecules must bind anions through strong electrostatic or weak hydrogen bonding and va n der Waals interactions. 4) Most anions exist in a narrow pH window, which could be problematic for host molecules that rely on

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19 hydrogen bonding interactions. The receptors may not be fully protonated in the pH range the anion exist, which would severely hinder the binding ability of the receptor.8-12 In the past forty years, many of these issues have been a ddressed by designing ligands with ammonium, guanidinium, amide, and Lewis acid moieties. Polyamine Receptors The first synthetic anion hosts 1-1, known as katapinands, were reported by Park and Simmons13 in 1968, and the encapsulation (Figure 11) of halides by these diammonium katapinands was proven by X-ray analysis in 1975 by Marsh et al.14 Unfortunately, the stability constants and selectivity of these hosts were rather low (Ks~102M in 50% deuterated TFA, Cl-/Br-~8).15 The study of supramolecular anion binding gained momentum when Lehn and coworkers reported the binding of halides by four protonated polyamine-based cryptates.16 Receptor 1-2-BT 6H+ (BT= bis-tren) (Figure 1-2) was shown to bind N3 with high stability constants, which was attributed to the six prot ons in a complementary a rrangement for the azide anion. This discovery opened the door to the development of a class of protonated polyaminebased receptors. Polyamine-based receptors are the most common synthetic anion receptors because of their many advantages. These receptors carry a pos itive charge and contain polar N-H bonds, producing conditions for the anion to bind via electrostatic and hydrogen bonding interactions. Also, this class of host is synthetically versatile, which allows for a wide range of multi-dentate frameworks with the desired solu bilities and geometries. Thus, these receptors are diverse and include linear, macrocyclic, macrobicylic, a nd macrotricylic polyammonium derivatives. The majority of polyamine-based receptors are cyclic. In acyclic molecules the two positively charged centers move away from each other to minimize unfavorable cation-cation interactions, which make acyclic polyammonium hosts poor candidates for the chelation of

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20 anions.17 In order to produce suitable polyammonium receptors, Lehn and coworkers synthesized nitrogen based macrocycles with large nitrogen separations (Figure 1-3). Macrocycles 1-3 through 1-5 form complexes wi th anions such as fumarate and squarate.18 Related receptors 1-6 and 1-7 were analyzed by X-ray crystallography to determine the receptors structural preference for ani on binding. The hydrochloride salt of host 1-6 binds two Clanions. One chloride anion is bound above, while the other is bound below the plane of the host. The hexahydrochloride salt of receptor 1-7 adopts a boat-shaped conformation, which binds a single chloride in the cleft of the host.19 Unfortunately, because the recep tors were too flexible many of the polyammonium macromonocycles do not bind anions selectively. To create anion receptors with greater selectivity, the hosts cavity must be relatively rigid, which reduces its ability to adapt to the size and geometry of the anion. Thus, selectivity can be gained by synthesizing receptors that ar e polycyclic. As mentioned above, the first reported anion receptor, bicyclic katapinands, displayed poor anion se lectivity due to the flexibility of the hydrocarbon linkages between the nitrogens. Therefore, receptor 1-8 (Figure 14) and the aforementioned host 1-2, which possesses more rigid macrocycles, should be better suited for the selectiv e binding of anions. Macrocycle 1-8, known as the soccer ball li gand, has a closed, rigid cavity with four widely spaced nitrogens,20 which is selective for Cl(log Ks>4).21 Receptor 1-2 was also found to be more selective than katapinand 1-1, but the large cavity size of 1-2 still allows for the binding of certain halides and azide.16 This receptors binding is only selective for anions with high charge density or multiply charged anions. In order to accommodate larger anions, katapinand and bis-tren receptors were extended with rigi d aromatic spacers to produce cyclophane receptors such as 1-9 and 1-10 (Figure 1-5). Host 1-9 is able to include one or even two bromide

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21 or iodide ions,22, 23 while cyclophane 1-10 shows an impressi ve degree of structural selectivity for a series of linear -dicarboxylate anions.24 Guanidinium Receptors Along with polyammonium receptors, the guanidinium ion (Figure 1-6) has been extensively studied because of its biological implications. Th e guanidinium ion is contained in arginine residues of enzymes, which play a major role in binding anionic substrates. Receptors with guanidinium moieties are also attractive because of th e guanidiniums high pKa (13.5), which allows the receptor to retain its pos itive charge and hydrogen bonding properties over a wide pH range.2 Lehn and coworkers discovered that macrocyclic receptors containing guanidinium moieties displayed weak bindi ng with bidentate species such as PO4 3due to the delocalized nature of the positive charge.25 Therefore, acyclic bifuncti onal receptors (Figure 1-7) were designed by Schmidtchen et al. to reduce the delocalization. Receptors such as 1-11 selectively bind malonate (Ks=16,500 M-1) in a deuterated methanol solution including a variety of dicarboxylates.26 The discovery by Schmidtchen has led to the continued study of guanidinium-based recep tors directed toward producing hosts capable of catalyzing biological reactions and transporting phosphates. Polypyrrolic Receptors Oligopyrrole-derived receptors have also been studied as possibl e anion hosts because they contain a combination of sp2 hybridized pyridine-like pyrrolic nitrogens as well as typical NH subunits. The combination of the different nitrogens has its advantages. Since the sp2 hybridized pyrrolic nitrogens are partially or completely protonated in neutral media, the receptor will have the ability to use both hydrogen bonding and electros tatic interactions.27 Free base porphyrins are unable to bind anions because the potential binding cavity is too small, but by adding pyrrole subunits or aromatic sp acers, as in receptors 1-12 and 1-13 (Figure 1-8), the

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22 macrocycle expands and anions such as Fand Clcan be accommodated. Host 1-12, synthesized by an improved procedure employed by the Sessler group, contains five pyrrolic hydrogens, which completely encapsulate F(Ks=1 X 105 M-1) in methanol.28, 29 The complete encircling of the anion by the macrocycle is highly favored and causes the discrimination of other halides by 1000-fold. The further expansion of the macrocyclic cavity by the addition of an anthracene spacer, 1-13, accommod ated the stronger binding of Clover Fin CH2Cl2.30 More recent studies have included a class of linear polypyrrolic receptors inspired by a family of naturally occurring tripyrro lic red pigments known as prodigiosins 31 (1-14) (Figure 19). Theses analogues bind anions such as Cl(Ka=105 M-1 in CH3CN) with high affinity, which is attributed to the hydrogen and electrostatic binding combination.32 In the case of analogues 115 a-c (Figure 1-10), their affinity for chloride is high and equal to that of the cyclic receptor 112. The introduction of an additi onal pyrrolic unit as we ll as electron poor cyano groups (1-16) further enhanced Claffinity (Ka=4.9 x 105 M-1).33 Neutral and Lewis Acidic Receptors All of the aforementioned examples of ani on hosts have carried a positive charge and used electrostatic as well as hydrogen bonding interactions to bind their guest. Neutral receptors, which can be purely organic or inor ganic, have also been studied. These receptors do not have to compete with other counter ions in the solution, so the measur ed binding constants are more representative of the absolute measure of the magnitude of binding. Neutral hosts also have the potential to be more selective because they do no t rely on non-directional electrostatic forces to achieve anion coordination.17 The majority of neutral anion binding recepto rs use Lewis acidic derivatives, such as boron, tin, and mercury, to complex various anio ns. Complexes 1-17, 1-18, and 1-19 (Figure 111) bind anions via bridging interactions between the Lewis acidi c centers. Chloride anions

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23 associate with 1-17 and 1-18, whic h are shared equally between the Hg atoms of 1-18, while 117 binds Clasymmetrically between the two B atoms.34 Complex 1-19 is a relative of katapinands but contains two Lewis acidic chloro-subs tituted centers. The host is more rigid and possesses greater anion affinity and sele ctivity, which is shown by receptor 1-19a (n=6) preferring Fwhile 1-19b (n=8) is selective for Cl.35 Lewis acidic heavy metals, such as lanthanide and actinides, have al so been found to bind anions. Rienhoudt and coworkers 36 synthesized bifunctional recept ors (1-20) that use a salen handle, in combination with a hydrophobic pocke t, to bind uranyl i ons along with anions (Figure 1-12). Complexes that contain cal ixarenes as a hydrophobic pocket weakly bind H2PO4 (Ks=400 M-1). The complexs binding constant sugge sts that the anion bi nds to the oxophilic uranium center. There is additional stabilization of the anion by hydrogen bonding interactions with the amide groups, which tether th e salen moiety to the calixarenes. Crystallographic data for complex 1-20 proved this binding configuration. Receptor 1-20 also includes an additional H2PO4 species, which is bound purely by hydrogen bonding interactions. The ability of complex 1-20 to be a hydrogen don or and acceptor is reflected by an increased binding constant (Ks=105 M-1) for H2PO4 -.37 OH Based Receptors Anions are essential for regulating osmotic pres sure, activatin g signal transduction pathways, maintaining cell volume, and in the production of signal tran sduction. Therefore, there are a large number of proteins and enzy mes that recognize anions such as phosphate, citrate, maleate, oxaloacetate, su lfate, glutamate, fumarate, and halides. Recently, X-ray crystal structures of many enzyme-anionic substrate complexes, such as DNA helicase Rep A, the sulfate-binding protein, and the phosphate-binding protein, show that these complexes do not rely on hydrogen bonding interactions from n itrogen based residues alone. Oxygen based

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24 residues from serine and threonine are also involved in the binding of the anion.38 Despite this evidence, there are very few examples of synthe tic anion binders that use alcohol moieties to bind anionic species. The first studies of anion receptors that in cluded only OH groups were reported in the early 2000s. In 2001 and 2003, Hong39 and Smith40 reported the binding of a variety of anions by the simple molecules azophenol and catechol. The azophenols could bind a variety of anions (binding constants were not reporte d), while the catechol preferred Clwith a low Kapp value of 1015 M-1.27 Other examples of this binding motif were not reported again until 2005 by Wang41 et. al, as well as Maitra42 and coworkers. Both groups observed anion binding through hydrogen bonding interactions with simple alcohol subun its, but larger complexes made from the monomers, 1-21 and 1-22 (Figure 1-13), had greater binding consta nts than those measured for the monomers. Unfortunately, these systems are not selective and extensive synthetic efforts would need to be employed in order to tune the selectivity of the receptor. In 2006, Scott group member Eric Libra was able to produce tunable and selective OH based anion receptors43 (Figure 1-14). Triphenoxymethane platforms (1-23) were tethered to one another through a salen backbone, which was then used to chelate square pl anar Ni(II) and Pd(II) ions (1-24a and 1-24b). The chel ation of the metal ions arrang ed the remaining OH donors into a tetrahedral binding pocket, which could selectively bind F-. Both complexes bind Fstrongly (log Ks=5.8) even in DMSO as well as produced pron ounced color changes up on the binding event. Research Objectives The use of O-H m oieties in anion binding re ceptors has been underexplored. This new class of receptors has properties that have the potential to indu ce strong and selective binding of anions. Therefore, the library and understand ing of anion receptors with O-H donors must be expanded. Our goal is to produce selectiv e, O-H based anion receptors using the

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25 triphenoxymethane platform, tripodal amines, and M (III) ions. The results of our approach to expand and understand anion receptors with O-H moieties are presented within. Figure 1-1. Illustration of the encapsulation of a ha lide ion by the diammonium katapinands. Figure 1-2. Depiction of a hexaprotonated bis -tren polyamine-based cryptate. Figure 1-3. Examples of polyammonium macromonoc ycles, which allow many positively charged nitrogen centers to exist is close proximity of one another.

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26 Figure 1-4. Depiction of a polyammonium marcotri cyclic receptor. The additional macrocycles increases the rigidity and selectively of the complex. Figure 1-5. Representation of cy clophane receptors. Rigid aromatic spacers were used to increase the size of the recepto r while restricting flexibility. Figure 1-6. Illustration of the bidentate ionic hydrogen bonds in a guanidinium salt.

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27 Figure 1-7. Illustration of bis-bicyclic guanidinium receptor generated by linking two bicyclic guanidinium groups with a rigid spacer. Figure 1-8. Illustration of olgi opyrrole-derived receptors. The original porphyrin macrocycle must be expanded to accommodate sm all anions such as fluoride. Figure 1-9. Depiction of prodigi osin 1-14. The derivative is pa rt of a family of naturally occurring tripyrrolic red pigments isolated for the microorganisms Serratia and Streptomyces

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28 Figure 1-10. Depiction of synt hetic linear polypyrrolic prodig iosin derivatives. The binding affinity can be tuned by changi ng the groups of the pyrrole ring. Figure 1-11. Depiction of neut ral Lewis acid receptors, which us e only Lewis acidic interactions to bind anions. Figure 1-12. Illustration of a bifunctional recepto r with a salen handle. The receptor can bind metal ions as well as anionic species.

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29 Figure 1-13. Representation of the large OH based receptors produced from monomers containing simple alcohol subunits. Figure 1-14. Depiction of the tr iphenoxymethane platform (1-23) in the all up configuration. The platforms can be tethered to one a nother through a salen backbone and used to chelate metal ions to form select ive anion receptors 1-24a and 1-24b.

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30 CHAPTER 2 ANION BINDING STUDIES WITH TRIPODAL METAL SALENS INCORPORATING TRIPHENOXYMETHANES Introduction Anion recep tors cannot rely on covalent in teractions, like cation receptors, to bind a targeted species. Therefore, simple molecules, such as crown ethers, which can selectively bind cations via size exclusion, cannot be used to coordi nate anionic species. Molecules used to bind anions must use other interacti ons to coordinate the species su ch as electrostatics, hydrogenbonding, and Lewis acid interactions. The majority of anion hosts use both electrostatic and Lewis acid interactions in combination w ith hydrogen-bonding or solely hydrogen-bonding interactions as binding motifs.1-2, 8-10 Based on this trend, it is crucial for syntheti c anion receptors to have donors capable of producing strong hydrogen-bonding interactions; ther efore, the acidic natu re of the hydrogenbonding donor must be considered. When describing and characterizing weak to moderate hydrogen bonds a solely electros tatic model can be used, whic h would describe a hydrogen bond as a coulombic interaction between a polar donor bond and an acceptor atom.44 Donors containing N-H motifs have been used extensivel y in synthetic receptors, and the protons in these various nitrogen based donors, such as pyrro les, amines, and pyridines have pKas ranging from ~26-44. Hydrogen bonding donors that have oxygen moieties, such as phenols, are more acidic with a pKa of ~10.0. The more acidic donor should provide hydrogens with more positive character, which should produce stronger hydr ogen-bonding interactions and higher binding constants for hosts with phe nolic binding pockets. Recently, solid-state structures of many enzyme -anionic substrate complexes as well as the ClC chloride channels of E. coli (Figure 2-1) have been obtained.45 The solid state structures prove that these complexes do not rely on hydr ogen bonding interactions from nitrogen residues

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31 alone. The oxygen-based residues of serine and threonine are also i nvolved in the binding of the anion. Despite the use of alcohol moieties in na ture, there have been few examples of synthetic anion receptors that use O-H donors to bind anions.40-42, 46-51 The discrepancy is largely due to how difficult it is to synthetically produce receptors that have O-H moieties in close proximity to one another, which also point toward one anothe r in space. Recent examples of anion binders with O-H donors meet these criteria41, 42, 51; however, the modification of these receptors in order to tune their selectivity would be synthetically labor intensive. Consequently, there is a need to produce receptors with ideally placed O-H donors th at form binding pockets, which can still be modified with little synthetic effort. A simple way to produce the required conditions is to tether the alc ohol moieties with a backbone that is able to chelate va rious metal ions. The metal will be used as a template that will position the alcohol functionalities near one another, producing th e desired binding pocket. By simply chelating a variety of meta ls with differing geometries and ionic radii, the receptor site can be easily modified. An ideal ligand for this a pproach would be a salen that incorporates the desired alcohol moieties. Salen and salen-type ligands are produced by a simple condensation of primary amines with various salicylaldehydes, known as a Schiff base reaction. The ligand chelates metals via the oxygens of the phenols and the ni trogens of the imines (Figure 2-2). The salen ligand system is versatile because of the numerous commercially available primary amines, which range from the simple ethylenediame to tripodal amines like tris (2-aminoethyl)amine (Tren). Also, salen ligands have been shown to stab ilize a variety of metals in va rious oxidation states such as square planar metals in a 2+ oxidation state and a large vari ety of transition metals and lanthanides with 3+ oxidation states.52-55

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32 Metal salen complexes made with salicylaldehyde cannot be used as anion receptors, so the salicylaldehyde must be modifi ed to carry additional alcohol groups ideally positioned to produce a binding pocket. A molecule which m eets these specifications is the aldehyde derivative of the triphenoxymethane platform, developed by Scott et. al.56-58 This platform can be easily produced by an acid-cat alyzed reaction of various para -substituted diformyl phenols (21a/b) with phenols (2-2a/b) substitut ed with alkyl substituents in one ortho and the para positions (Figure 2-3). The alkyl substituents not only protect against unwanted reactions at the ortho and para positions, they also allow for an easy way to tune the solubility of the resulting platform. In this reaction, only one aldehyde group of the diformyl phenol is able to react before the aldehyde derivative of the triphenoxymethane platform precipitates out of the solution. Most importantly, previous work with this molecule has shown that the platform adopts an all up configuration,56-58 which means that in both soluti on and the solid state the alcohol groups all point in the same direction, up, with respect to the central methine hydrogen (Figure 24). Once the platforms are tethered by a sale n backbone and brought into proximity to one another by metal chelation, a bind ing pocket that contains four to six phenol donors should be formed. Work done by previous members of the Scott group 43, 59 has shown that the aldehyde derivative of the triphenoxymethane platform reacts with various diamines to produce salen ligands. Like the original salen ligand, various metal ions (Mn(II), Ni(II), Zn(II), and Pd(II)) were incorporated into the tr iphenoxymethane salen. The me tal was chelated by the same binding motif as seen in previous salen systems, and there was no evidence that the metal reacted with the remaining phenols of the triphenoxym ethane platform. The uncoordinated phenols remain in the all up conformation, which crea ted a binding pocket with four O-H donors.

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33 The Ni (II) and Pd (II) triphenoxymet hane salen complexes with an R, Rcyclohexyl backbone (Figure 1-14) selectively bind fluoride. In order to expand our ligand library and understanding of anion receptors with O-H donors, focus was placed on producing triphenoxymethane salens using the tripodal am ines 1,1,1-Tris(aminoethyl)methane (tame) and Tris(2-aminoethyl)amine (tren). These salen ligands chelate various transition metals and lanthanides in the 3+ oxidation state to produce binding poc kets with six O-H donors. The resulting molecules were tested for anion incorporation via 1H NMR and UVvis spectroscopy. Results and Discussion As de monstrated by Libra et al.,43 metal triphenoxymethane sale ns 1-24 a/b (Figure 1-14) contain O-H based binding pockets, which select ively bind fluoride. We envisioned expanding the library of metal triphenoxymethane salens in hopes of finding receptors that could bind larger and more complex anions. Therefore, triphenoxymethane salens made with commercially available tripodal amines were explored. Pr oducing triphenoxymethane salen ligands with tripodal amines has several advantages. 1) The binding cavity has an increased number of accessible O-H donors. 2) Due to the increased fl exibility of the metal binding site, a greater number of metals are available for possible chelation. 3) Metal complexes with lanthanides in the 3+ oxidations state could bind anions vi a hydrogen bonding as well as Lewis acid interactions. Triphenoxymethane Salens with Tren Following the general approach for producing triphenoxym ethane salens, a solution with three equivalents of 2-3a/b in refluxing absolute ethanol was treated with one equivalent of Tren (Figure 2-5). The resulting bright yellow precipitates were th e desired ligands 2-4a/b. All triphenoxymethane salens were characterized by 1H NMR spectroscopy. The spectra showed

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34 that the Schiff base reaction converted clean ly giving one major product. The reaction conditions produced the triphenoxymet hane salens in high yields a nd in multi-gram quantities. Metallation of Tren Triphenoxymethane Salen 2-4a N(1), N(2/2a/2b) and O(1/1a/1b) of the triphenoxym ethane sale ns allow for the coordination of lanthanides, which can accommodate the coordina tion of seven to nine atoms. For the initial attempt to metallate the ligand 2-4a, La (III) wa s chosen for its ability to produce a neutral diamagnetic complex, allowing for the quick de termination of metal complex formation by 1H NMR spectroscopy. Metallation of 2-4a was accomplished by using a modified literature procedure.55 A boiling acetonitrile solution of ligan d 2-4a was treated with one e quivalent of La(III) Triflate (Figure 2-6). Within a few mi nutes a light yellow precipitate formed, which was analyzed via 1H NMR spectroscopy. Many of the char acteristic features of the 1H NMR spectrum of triphenoxymethane salen 2-4a changed upon the me tallation. For instance, the singlet arising from the phenolic oxygens (O(1/1a/1b)) disappears. Also, the appearance of two triplets and two doublets in the region of 4.5-2.5 ppm a singlet at 2.15 ppm, as we ll as singlet at 1.06 ppm were additional diagnostic changes when complex 2-4a-La(III) was produced. Single crystals of 2-4a-La(III) were obtained fr om the slow diffusion of a large variety of solvent combinations, which produced two dis tinct solid-state stru ctures: 2-4a-La(III) CH3CN (Figure 2-7) and 2-4a-La(III) THF (Figure 2-8). All solvent co mbinations that excluded THF produced 2-4a-La(III) CH3CN, while any combination that included THF produced 2-4aLa(III) THF. The solid-state structure of the 2-4a-La(III) CH3CN shows a C3 symmetric, sevencoordinate metal complex with a relative potentia l binding pocket of 6.312 The relative size

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35 of the potential binding is determined by measuring between the only fixed positions in the binding arms, which are the methine carbons. La(II I) is bound to all three oxygens of the salen phenols (La(1)O(1/1a/1b) 2.341(5) ) as well as three of the four nitrogens (La(1) N(2/2a/2b) 2.674(7) ) of the Tren subun it. The metal is not bound to the apical nitrogen (N1), but coordinates an acetonitrile (La(1) N(3) 2.795(9) ) to satisfy its coordination requirements. The coordination of the metal produces a twist in the molecule, which accounts for the splitting of the two alkyl signals (3.39 and 2.79 ppm) into four signals (4.06, 3.21, 3.03, and 2.58 ppm) upon metallation. The tw isting of the backbone causes the four protons to become magnetically distinct. The coordinated acetonitrile molecule also influences the overall structure of 2-4aLa(III) CH3CN. The six phenol subunits that are not i nvolved in the metal chelation can be split into two distinct groups of three phenols. In the first group, three of the phenols hydrogen bond to the phenolate oxygens, O(1/1a/1b), with O O distances of 2.708. The position of the second group phenol subunits is influenced by th e protons of the coordinated acetonitrile, which point toward the center of -system of each phenol ring. The coordinated solvent molecule prevents the phenolic oxygens from pointing toward one another in the solid-state. The distinct positions of the phenol subunits also caused the methyl and t -butyl substituents to become magnetically distinct, which produced the appearance of the 1H NMR signals at 2.15 and 1.06 ppm. Complex 2-4a-La(III), in the presence of TH F, will preferentially bind the THF molecule in order to satisfy its coordination requirement s (Figure 2-8). The THF molecule causes the solid-state structure of 2-4a-L a(III)THF to become pseudo-C3 symmetric and to increase the relative size of the potential binding pocket of 2-4a-La(III)CH3CN by ~1.217 to 7.529

PAGE 36

36 This data was encouraging because it establis hed that the acetonitrile molecule could be displaced and that some degree of flexibil ity existed in the binding pocket. The La(1) O(1/2/3) and La(1) N(2/3/4) distances and the in tramolecular hydrogen bonds for 24a-La(III)THF are nearly identical to the corresponding distances in 2-4a-La(III) CH3CN. The 1H NMR spectrum of 2-4a-La(III)THF is al so similar to that of 2-4a-La(III) CH3CN, which shows only small shifts of the aromatic pr otons and the presence of a bound THF molecule (La(1) O(10) 2.6032(18) ). It was also important to determine if the si ze of the metal ion used in the complex would affect the binding pocket enough to change the bindi ng properties of the receptor. Therefore, efforts were made to synthesize Eu(III) and Lu( III) triphenoxymethane sale ns. The metal ions are found in the middle and end of the lanthanide se ries and are approximately 8% and 15% smaller than La (III) respectively. Complex 2-4a-Eu(III) was prepared by usi ng the same method employed to produce 24a-La(III) (Figure 2-6). It was more difficult to characterize 2-4a-Eu(II I) because Eu(III) is a paramagnetic metal, which usually means that 1H NMR spectroscopy cannot be used to monitor the synthesis of the compound due to severe broadening of the 1H NMR signals. However, the 1H NMR spectrum of the resulting precipitate was readable and contained a few broad and several sharp signals ranging from 37.30 ppm to -34.72 ppm. The production of the complex was confirmed wh en single crystals of 2-4a-Eu(III) were obtained from the slow diffusion of a variety of solvent combinat ions, giving the structure 2-4aEu(III) CH3CN (Figure 2-9). All solvent combina tions that included THF did not produce crystals suitable for X-ray diffraction.

PAGE 37

37 The solid-state structure of 2-4a-Eu(III) CH3CN shows a C3 symmetric, seven coordinate metal complex with a slightly smaller relative pot ential binding pocket, 6.273 than that of the 2-4a-La(III) CH3CN. The Eu (III) ion is bound to all three oxygens of the salen phenols (Eu(1) O(1/1a/1b) 2.243(3) ) but to only three of the four nitrogens (Eu(1) N(2/2a/2b) 2.547(4) ). As seen in the soli d-state structure of 2-4a-La(III) CH3CN, the metal in the Eu (III) analogue does not bind to the api cal nitrogen (N1) and prefers to coordinate an acetonitrile molecule (Eu(1) ) N(3) 2.758(5) ) as a means to sati sfy its coordination requirements. Efforts were also made to produce the Lu (III) analog. Because Lu (III) is a diamagnetic metal, the metallation of ligand 2-4a could be monitored through 1H NMR spectroscopy. Unfortunately, the synthetic rout e used to produce 2-4a-La(III) CH3CN and 2-4aEu(III) CH3CN did not produce the desire d Lu (III) complex. Other routes were employed and a variety of solvents were used; however, the Lu (III) complex was never produced, which was most likely due to the bulk of the ligand. Metallation of Tren Triphenoxymethane Salen 2-4b Attem pts to synthesize complex 2-4b-La(III) using the synthetic route shown in Figure 2-6 produced reaction mixtures with 1H NMR spectra that did not exhibit the indicative changes attributed to the successful metallation of 2-4b. Therefore, an alternat ive synthetic route was employed in an effort to synthesize th e desired metal complex (Figure 2-10). Initially, two equivalents of Tren were a dded to a methanol so lution of La(III)(CF3SO3)3. The resulting mixture was treate d with three equivalents of 2-3b. The reaction mixture did not produce an isolable solid, and the 1H NMR spectra of that mi xture showed that only triphenoxymethane salen 2-4b was produced. The procedure was repeated using

PAGE 38

38 La(III)(NO3)3H2O as the metal salt, and these reaction conditions produced a light yellow precipitate. The 1H NMR spectrum of the yellow solid did not have the signal pattern expected for 24b-La(III). The signal at 12.53 ppm, the phenolat e proton, disappeared, which would usually indicate the formation of a metal complex. Howe ver, the region associated with the methylene protons of the Tren subunit did not correspond with the signals in the 1H NMR spectrum of 2-4aLa(III). The signals for the yellow solid consisted of two triplets and two doublets, but not in the same order, as well as a singlet Based on this data alone, it was not possible to conclusively determine the product of th e reaction. Fortunately single crystals of th e product were grown and the solid-state structure of 2-4b*-La(III) was determined (Figure 2-11). The solid-state data shows that during the reaction one amine of Tren subunit was unable to react with 2-4b before the resu lting complex precipit ated out of solution, which explains the anomalies in the 1H NMR data. According to th e structural data, La (II I) is nine coordinate: six of the bonds from a combination of the Tren nitrogens (La(1) N(1/2/3/4) 2.802(6) 2.708(6), 2.674(6) 2.685(6) ) and phenol oxygens (La(1) O(1/2) 2.334(4) 2.357(4) ), one from the nitrogen of an acetonitrile molecule ((La(1) N(6) 2.731(6) ), and the final two from the bidentate coor dination of nitrate (La(1) O(3/4) 2.668(6) 2.666(6) ). Though 2-4b*-La(III) would not be an ideal anion receptor, it is ideal for producing asymmetric anion receptors. The complex could be treated with a variety of aldehydes, which could influence the solubility as well as the anion binding properties of the resultin g metal complex. Unfortunately, all attempts to attach another triphenoxyme thane aldehyde derivative were unsuccessful.

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39 Anion Binding Studies of 2-4a-La(III) CH3CN, 2-4a-Eu(III) CH3CN and 2-4a-La(III)THF Previous Scott group member, Dr. Eric Li bra, produced complexes 1-24a and 1-24b (Figure 1-14), which contained four phenol donor s. The tetrahedral binding pocket was ideal for the small, spherical anion fluoride. However, many anions of interest have more complex structures and therefore ligands with larger binding pockets and an increased number of donors would be better suited for accommodating these anions. Complex 2-4a-M(III) was envisioned to accommodate large anions such as perchlorate or phosphate. The lanthanide complexes could stabilize the anion thr ough a Lewis acidic interaction as well as hydrogen bonding interactions from the OH donors (Figure 2-12). In order to determine the ab ility of 2-4a-La(III)/Eu(III)CH3CN to bind various anions, a solution of the complex was treated with a sma ll amount of the tetrabutylammonium salt of the desired anion. If the anion binds to the receptor, there are changes in 1H NMR spectra and/or UV-vis spectra of the receptor. With 1H NMR spectroscopy, binding is signified with the disappearance or shift of the phenol signals. Changes in the other proton signals can also occur, but these changes are greatly dependent upon the conformational adjustments that occur to accommodate binding the anion. With UV-vis spectro scopy, the spectrum typically red shifts as the receptor binds the anion. When testing 2-4a-La(III)CH3CN and 2-4a-Eu(III)CH3CN for anion binding ability, the data suggested that the anions fell into two di stinct groups. When the first group of anions (ClO4 and NO3 -) was added to a solution of either recep tor, no discernable changes were present in the 1H NMR or UV-vis spectra. This data indicates that neither 2-4a-La(III)CH3CN nor 2-4aEu(III)CH3CN binds nitrate or perchl orate anions. Conversely, upon the addition of the second group of anions (H2PO4 -, F-, Cl-, and Br-), the 1H NMR and/or UV-vis spec tra of the solutions showed noticeable changes.

PAGE 40

40 There were some unforeseen challenges when testing the 2-4a-La(III)CH3CN complex. Upon, the addition of the second group of anions, the 1H NMR resonances associated with 2-4aLa(III)CH3CN gradually disappear and shift. As more of the anion is ad ded to the solution a new set 1H NMR peaks appear (Figure 2-13). The signa ls (indicated by the in Figure 2-13) that arise have the same chemical shifts as th e protons associated with compound 2-4a. Thus, it appears that the metal is released from 2-4a-La(III)CH3CN leaving ligand 2-4a in solution. The extent to which the metal is released from 2-4a-La(III)CH3CN depends upon the anion added to the solution. Upon the addition of one equivalent of fluoride or phosphate, the 1H NMR spectrum indicates that the solution cont ains only 2-4a. Conversely, when Clor Bris added to the 2-4a-La(III)CH3CN solution, the metal is released to a lesser extent. Fo r these anions, the 1H NMR data suggests that only 20-30% of the 2-4a-La(III)CH3CN is demetallated with the addition of one equivalent of the species. When receptors bind anions the UV-vis absorb ance of the receptor typically red shifts. The absorbance of both 2-4a-La(III)CH3CN and 2-4a-Eu(III)CH3CN blue shifted to varying degrees upon the addition of th e anion salts. The addition of one equivalent of ClO4 and NO3 showed no change in the UV-vis absorbance of 2-4a-La(III)CH3CN or 2-4a-Eu(III)CH3CN, while the addition of one equivalent of For H2PO4 gave the same absorbance as that of compound 2-4a. Large excesses of Cland Brwere required in order for the absorbance to read the same as the absorbance for compound 2-4a. When solutions containing 2-4a-La(III)TH F were treated with the above-mentioned anions, the metal complexs behavior varied from that of 2-4a-La(III)CH3CN. When the desired anion is added to the 2-4a-La(III)THF solution, even in amounts exceeding one equivalent, the 1H NMR spectrum of the recep tor does not change. The 1H NMR data suggests

PAGE 41

41 that 2-4a-La(III)THF is more stable than 2-4a-La(III)CH3CN because it is not susceptible to demetallation by the anion salts; however, the data also indicates that 2-4a-La(III)THF does not bind anions either. This conclusi on is also supported by data co llected from UV-vis experiments that show no noticeable red or blue shift in the absorbance peak of 2-4a-La(III)THF upon the addition of the studied anions. The behavior of 2-4a-La(III)THF is most lik ely due to the bound THF molecule itself. While the THF molecule allows 2-4a-La(III)THF to be more stable than 2-4a-La(III)CH3CN, it also hinders the complexs ab ility to bind anions. The 1H NMR spectrum of the complex clearly shows a bound THF molecule, and when 2-4a-La(III) THF is treated with the anions the signal for the THF molecule does not move in the spectrum, which indicates that the THF is never released by the La (III) metal center and consequently blocks the O-H binding pocket. In the end, it was determined that wate r caused the demetallation of 2-4a-La(III)CH3CN and 2-4a-Eu(III)CH3CN. 1H NMR spectra of 2-4a-La(III)CH3CN in CDCl3 or CD2Cl2, which were left open to the air, show gradual demetallation of 2-4a-La(III)CH3CN to compound 2-4a over a period of approximately one week. On the other hand, a sample of 2-4a-La(III)CH3CN in CD2Cl2 that was prepared in an inert atmosphe re showed only trace amounts of demetallation over a period of two weeks. This would also ex plain the variation in th e amount of demetallation during the time of the experiment. All of the anion salts are hydrated to varying degrees, which means the receptor being studied would be exposed to differing amounts of water during the experiment. Triphenoxymethane Salens with Tame Following the general approach for producing triphenoxym ethane salens, a solution with three equivalents of 2-3a or 2-3b in refluxing absolute ethanol was treated with one equivalent of Tame (Figure 2-14). The resulting bright ye llow precipitates were th e desired ligands 2-5a and

PAGE 42

42 2-5b. All triphenoxymethane sale ns were characterized by 1H NMR spectroscopy. The spectra showed that the Schiff base re action converted cleanly giving one major product. The reaction conditions produced pure products in high yi elds and in multi-gram quantities. Efforts to produce single crystals of ligand 2-5a by slow diffusion or evaporation were unsuccessful, but single crystals suitable for X-ray diffraction of ligand 2-5b were grown by a slow diffusion of methanol into THF. The solid -state structure (Figur e 2-15) shows that the tripodal amine is large enough to tether three triphenoxymethane platforms, and upon formation of Schiff base, each platform remains in the a ll up orientation. The solid-state data shows intermolecular hydrogen bonding as well as intramolecular hydr ogen bonding between N(2/2a/2b) and the hydrogen on O(2/2a /2b) with N-O distances of 2.625 Metallation of Tame Triphenoxymethane Salen 2-5b Attem pts to coordinate both La (III) and the smaller Lu (III) with 2-5a and 2-5b using the previously mentioned synthetic ro utes were unsuccessful, which could be due to the large size of the La(III) and Lu(III) ions (1.17 and 1.00). Therefore, efforts were made to produce a complexes with the smaller, six coordinate Co(I II) and Fe(III) in hopes that the metal complexes produced would be less likely to de metallate in the presence of th e hydrated anion salts used in the anion binding experiments. Metallation of the ligand 2-5b was accomp lished by using a modified literature procedure.60 A solution of 2-5b was treated with Cobalt (II) acetate tetrahydrate in methanol. The resulting 2-5b-Co(II) complex was oxidized to the 2-5b-Co(III) complex upon the addition of a mild hydrogen peroxide so lution (Figure 2-16). The produc t mixture was purified via a short plug of neutral alumina. The dark brown solid was analyzed via 1H NMR spectroscopy. Many of the characteristic features of the 1H NMR spectrum of triphenoxymethane salen 2-5b changed upon the metallation. For instance, the singlet (13.35 ppm) arising from the phenolic

PAGE 43

43 oxygens (O(1/2/3)) disappears. The appearance of two doublets in the region of 3.6-3.0 ppm, two singlets at 1.86 ppm and 1.69 ppm, as well as the shifting of a singlet to 1.99 ppm were additional diagnostic changes when complex 2-5b -Co(III) was produced. Single crystals of 25b-Co(III) were obtained from the slow diffusion of a large variety of solvent combinations; however, the best structure of th e complex was obtained from CHCl3/MeOH (Figure 2-17). The structural data shows that the 2-5b-Co(III) complex is pseudo-C3 symmetric. The average distance between the th ree methine carbons is 5.475 and there is no indication of intramolecular hydrogen bonding between the atoms of the complex. As would be expected for this complex, the Co(III) center is six-coordinate and therefore does not need to bind a solvent molecule in order to satisfy its coordination requirement. The Co(III) ion is bound to all three oxygens of the salen phenols (Co(1) O(1/2/3) 1.890(3) 1.892(3) 1.903(3) ) as well as all three nitrogens (Co(1) N(1/2/3) 1.908(4) 1.909(4) 1.905(4) ). As seen in the 2-4a-La(III)CH3CN complex, the binding of the phenol oxygens by the Co(III) in solution corresponds with the disa ppearance of the peak at 13.35 ppm in the1H NMR spectrum. The coordination of the metal also produ ces a twist in the molecule. This twist causes the two protons between the apical carbon and imine to be magnetically distinct, which is supported by the appearance of two distinctive chemical shifts (3.56 ppm and 3.07 ppm) in the 1H NMR spectrum. Lastly, the metal chelation also causes each set of methyl groups to become magnetically distinct, causing the appearance of two additional signals (1.86 ppm and 1.69 ppm) in 1H NMR spectrum. Complex 2-5b-Fe(III) was prepared by treati ng 2-5b with one equivalent of Fe (III) perchlorate (Figure 2-16). Passing the com pound through a short plug of neutral alumina purified the purple product. Complex 2-5b-Fe(III) was more difficult to characterize because Fe

PAGE 44

44 (III) is a paramagnetic metal and 1H NMR spectroscopy cannot be used to monitor the synthesis of the compound due to severe broadening of the 1H NMR signals. Fortunately, the production of the complex was confirmed when single crystals of 2-5b-Fe(III) were obtained from the slow diffusion of pentane into dich loromethane (Figure 2-18). The structural data shows that the 2-5b-Fe(III) complex is pseudo-C3 symmetric. The average distance between the three methine carbons is 5.632 which is slightly larger than the corresponding Co(III) complex, and there is no indication of intramolecular hydrogen bonding between the atoms of the complex. As would be e xpected for this complex, the Fe (III) center is six-coordinate and therefore does not need to bi nd a solvent molecule in order to satisfy its coordination requirement. The Fe(III) ion is boun d to all three oxygens of the salen phenols (Fe(1) O(1/2/3) 1.917(2) 1.958(2) 1.962(2) ) as well as all three nitrogens (Fe(1) N(1/2/3) 2.169(2) 2.155(2) 2.147(2) ). Anion Binding Studies of 25b-Co(III) and 2-5 b-Fe(III) In order to identify the 1H NMR signal attributed to the phenol protons in the potential binding pocket, a solution of 2-5b-Co(III) in CDCl3 was treated with a drop of D2O and allowed to stir overnight. The signals at 6.225 ppm a nd 5.799 ppm disappeared due to the exchange of the phenolic protons for deuterium atoms. The spect rum also displayed shifts of all of the proton signals in the aromatic region, ranging from 0.4 1 to 0.136 ppm, which was most likely caused by the conformational changes cause d by the encapsulation of D2O by 2-5b-Co(III). However, there were no evident shifts in the signals a ttributed to the alkyl protons. Because the anion sources used in the binding experiments contain wa ter, it would be difficult to determine with any certainty if the receptor has bound an anion based on the small shifts in the aromatic region

PAGE 45

45 alone. As a result, a better indication of bindi ng would be the disappearance or shifting of the two phenol signals coupled with shifts in the aromatic as well as the alkyl signals. The spectra of 2-5b-Co(III) s how shifts in the aromatic and alkyl signals upon the addition of F-, Cl-, NO3 -, or ClO4 -. The shifts in the spectra with Cl-, NO3 -, or ClO4 are insignificant compared to the shifts in the spectra of 2-5b-Co(III) when treated with F-. In addition, in these spectra the phenol signals remai n, while the two phenol signals disappear in the spectrum of 2-5b-Co(III) with F-. Since the shifting of the prot on signals could be due to the water in the anion source, UVvis experiments would be a better way to determine if 2-5bCo(III) does in fact bind any of the tested anions. Solutions containing complex 2-5b-Co(III) a nd complex 2-5b-Fe(III) were monitored for changes in UV-vis absorbance as each anion was added. Complex 2-5b-Fe(III) was monitored by UV-vis experiments only because Fe(III) is paramagnetic. After the addition of the tetrabutylammonium salts of F-, Cl-, NO3 -, or ClO4 to the solution, the UV-vis absorbance for both complexes did not change. The addition of a large excess an ion did not change the UV-vis absorbance of the solutions either, which sugge sts that neither 2-5b-Co(III) nor 2-5b-Fe(III) bind any of the anions tested. However, the disappearance of the O-H signals in 1H NMR spectrum of 2-5b-Co(III) and fluoride suggested that perhaps binding was stil l occurring even if the UV-vis absorbance was not changing. Therefore, the environment of the Fwas monitored with 19F NMR as it was added to a solution of 2-5b-Co(III) in CDCl3. First, a solution of tetrabutylammonium fluoride in CDCl3 was treated with a single drop of a dilute solution of the standard CFCl3, showing that tetrabutylammonium fluoride in a CDCl3 solution has a of -129.53 ppm with respect to CFCl3. Upon the addition of fluoride up to one equivalent, the 19F NMR spectrum shows a peak at

PAGE 46

46 -129.53 ppm. As more fluoride is added to the solution, past one e quivalent, the signal at -129.53 ppm continues to grow and no othe r peaks are present in the spectrum. The data from the 19F NMR experiments suggests that 2-5b-Co(III) does not bind fluoride. Upon a closer inspection of the 1H NMR spectrum of 2-5b-Co(III) in the presence of fluoride shows a gradual growth in the signal at 7.26 ppm Therefore, the fluoride is promoting the exchange of the deuterium in the solvent with the phenolic protons, incr easing the concentration of CHCl3. The deuterium-proton exchange also occurred when 1-24a-Pd(II)/Ni(II) was treated with fluoride in CDCl3 and (CD3)2CO43 and is known to happen with receptors containing amides.61 The experiment was repeated in DMSO-d6 to prevent the exch ange. Many of the proton signals of 2-5b-Co(III) shifted as fluoride was adde d to the solution, but the 19F NMR spectrum showed only the signal associated w ith tetrabutylammonium fluoride in DMSO-d6 (-104.46 ppm) with respect to CFCl3. Based on the 1H and 19F NMR studies, the shifting of th e proton signals of 2-5b-Co(III) upon the addition of the anion salt appeared to be due to the incorporation of water as opposed to fluoride by the phenolic pocket. This conclusi on was supported by solid-state data of single crystals obtained from a mixture containing 2-5b-Co(III) as well as tetrabutylammonium fluoride. The solid-state structure of 2-5b-Co(III)-H2O (Figure 2-19) shows a water molecule held in the cavity by two unequal hydrogen-bonding interactions with O O distances of 1.866 and 2.203 The structural data also shows th at the binding cavity of 2-5-Co(III) is flexible like that of complex 2-4a-La(III), and in order to accommodate the water molecule the phenolic pocket expands ~ 0.4 giving an average distan ce between the central methine carbons of 5.846 When compared to 2-5-Co(III), the expans ion of the cavity below the metal center does not significantly affect the Co-O or Co-N bonds.

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47 Twist Angles of Pseudo-Helical Lantha nide and Transition Metal C omplexes The chelation of lanthanide and transition metals by ligands 2-4a and 2-5b produce seven or six-coordinate metal complexes that are ps eudo-helical. Three distinct complexes were produced with ligand 2-4a: 2-4a-La(III)CH3CN (Figure 2-7), 2-4a-La (III)THF (Figure 2-8), and 2-4a-Eu(III)CH3CN (Figure 2-9). The metals in a ll three complexes bind to three imino nitrogens (N2, N2, and N2), th ree phenolic oxygens (O1, O1, and O1), as well as an atom from a solvent molecule. The apical nitrogen (N1) is not involved in the metal chelation in any of the aforementioned complexes. Both the La(III) and Eu(III) complexes that included an acetonitrile molecule are C3 symmetric, while the La(III) complex with a bound THF molecule is pseudo-C3 symmetric. Two metal complexes were produced with ligan d 2-5b, 2-5b-Co(III) (Figure 2-17) and 2-5b-Fe(III) (Figure 2-18), fo rm bonds with the three imino nitrogens (N1, N1, and N1) and three phenolic oxygens (O1, O1, and O1), giving two pseudo-C3 symmetric complexes. The three lanthanide and the tw o transition metal complexes appear to have similar triple pseudo-helical structures; however upon closer study of the metal core of each complex (Figure 2-20 and 2-21) it was found that the values of the twist angles varied. The first angle considered was the dihedral angle defined by C1-N1-M1-O1 for the lanthanide complexes and C3-C2-M1O1 for the transition metal complexes. For th e three lanthanide complexes, 2-4a-Eu(III)CH3CN has the greatest twist angle (59.9 ), while complex 2-4-La(III)CH3CN has the smallest twist angle (50.9 ). The presence of the larger THF molecule in 2-4-La(III)THF increases the angle (58.5) to one comparable to the distortion seen in the Eu(III) compound. When comparing the twist angles of the two transiti on metal complexes, 2-5b-Co(III) (81.0 ) with the smaller metal ion has a dihedral angle ~16.0 larger than that of the corresponding Fe(III) complex (65.2 ).

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48 In order to determine the differences in the helicity of each metal complex, the metal core of each compound was partitioned into four planes (Fi) for the lanthanide compounds (F1= the plane containing C1, C1, C1, F2 = C2, C2, C2, F3 = N2, N2, N2, F4 = O1, O1, O1) and three planes for the transition metal complexes (F1 = the plane containing C3, C3 C3, F2 = N1, N1 N1, F3 = O1, O1, O1). Using a previously reported method,55 the helical revolution about the C3 axis can be quantified from the portions of the metal containing core. The distances between the planes are known as di, and the twist angles in each portion, wi, are defined by the average dihedral angles C1-N1-M1-C2 ( w1), C2-N1-M1-N2( w2), and N2-N1-M1-O1( w3) for the lanthanide complexes and C3-N1-M1-C2 ( w1) and N1-C2-M1-O1 ( w2) (Table 2-1) for the Co(III) and Fe(III) containing compounds.55 As seen in Table 2-1, the values d1-d3 for the three lanthanide complexes were not significantly effected a change in the coordinated solvent molecule or by the size of the metal ion. When compared to similar complexes55, which do not contain a coordinated solvent molecule, d1 and d2 are comparable but the d3 values for 2-4a-La(III)CH3CN and 2-4aLa(III)THF are 0.408 and 0.612 smaller than the corresponding seven-coordinate La(III) complex. These values are similar or smaller than the d3 values reported for complexes with smaller metal ions such as Y(III) (2.167 ) a nd Lu(III) (2.064 ). For the two transition metal complexes 2-5b-Co(III) and 2-5b-Fe(III), both di values are affected by the change in the size of the metal ion present in the complexes. Using the smaller Co(III) ion produces a d1 value 0.571 larger as well as a d2 value 0.186 smaller than the corresponding di values for the Fe(III) complex. When comparing the measured twist angle values wi, the data shows that like the previously reported lanthanide complexes the ov erall twist angle of the helices are mainly

PAGE 49

49 influenced by the contribution from w3, while the twist of the transition metal complexes are dictated by w2. The decrease in the ionic radius of the transition metal complexes appears to increase the torsion angl es of the complex by 15.8 which suggests that the nanostructure of a family of similar metal complexes could be adjusted by choosing the appropriate transition metal. For complexes 2-4a-La(III)CH3CN, 2-4a-La(III)THF, 2-4a-Eu(III)CH3CN, the w3 values are significantly larger, which correspond s to larger overall to rsion angles (50.8, 58.6, 59.9) than any of the previously studied lantha nide complexes (torsion angles ranging form 27.3(La(III)) 47.7 (Lu(III)). This data suggests that introducing a solvent molecule to the coordination sphere of the lanthani de ion can also be used to ad just the nanostructure of sevencoordinate lanthanide complexes. Conclusions The aldehyde derivative of th e triphenoxym ethane platform was used in a Schiff base reaction with the amines Tren and Tame to pr oduce large, tripodal sale ns. Tren and Tame triphenoxymethane salens were successfully meta llated using various lant hanide and transition metal salts. The resulting metal triphenoxymethane salens readily formed single crystals suitable for X-ray diffraction, and the solid-state stru ctures show that the metallation of the triphenoxymethane salens produced welldefined O-H based binding pockets. The La(III) and Eu(III) Tren tri phenoxymethane salens were tested with a variety of tetrabutylammonium anion salts, and were found to be unstable. The water in the anion salts caused the demetallation of the complexes, thus destroying the binding pocket. The less labile Co(III) and Fe(III) Tame triphenoxymethane salens were also tested with the same anion salts. The metal complexes were found to be stable in the presence of the anions, but there was no indication that either metal salen bound any of the anions tested.

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50 Experimental 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 analys es and Mass spectrometry were performed at the in-house facilities in the De partment of Chemistry at the University of Florida. All solvents were ACS or HPLC grade and used as purchased. 2-tert-butyl-4-methylphe nol (2-2a) and 2,4dimethyl-phenol (2-2b) were purchased and used as received. 2,6-diformyl-4-methylphenol62 and compound 2-3a57 were prepared as previously described. General Procedure for the Synthesis of Compounds 2-3 1 m L aliquots of TFA were added to a mixt ure of 2,6-diformyl-4-a lkylphenol (2-1) and 2,4-alkylphenol (2-2) until th e solids dissolved (for 2-3a) or th e solution turned bright red (for 23b). The solution was stirred for 24 hours. During this time, a solid precipitated from the oily mixture, which was washed with a minimal amount of cold methanol, collected via filtration, and dried to obtain the pu re desired product. Compound 2-3b Using 8.00 g (48.78 mmol) of 2,6-diform yl -4-methylphenol (1-1b) and 16.29 g (133.33 mmol) of neat 2,4-dimethylphenol (12b) afforded 8.28 g (43%) of product. 1H NMR [CDCl3] = 11.26 (s, 1H), 9.83 (s, 1H), 7.24 (s, 1H), 7.06 (s, 1H), 6.86 (s, 2H), 6.50 (s, 2H), 6.11 (s, 1H), 3.95 (bs, 2H), 2.27 (s, 3H), 2.19 (s, 6H), 2.16 (s, 6H). 13C NMR [CDCl3] = 196.84, 157.09, 149.97, 138.52, 132.56, 130.79, 130.21, 129.63, 127.53, 127.06, 124.63, 120.32, 37.85, 20.93, 20.79, 16.17. DIP-CI-MS: calcd for C25H26O4 390.1831; found 390.1816 [M]+.

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51 General Procedure for the Synthesis of Compounds 2-4 Com pound 2-3 was added to 250 mL of absolute ethanol. The resulting solution was brought to a reflux. A solution of tris(2-aminoethyl)amine (Tren) (5 ml of absolute ethanol) was added to the refluxing ethanol mixture, which immediately turned bright yellow. The mixture was refluxed for 12 hours. The pure product was colle cted by filtration (for 2-4b) and dried, or isolated by precipitation with water (for 24a), collected via fi ltration, and dried. Compound 2-4a Using 2.24 g (4.73 mmol) of com pound 1-3a a nd 0.23 g (1.57 mmol) of Tren afforded 3.29 g (94%) of product. 1H NMR [CDCl3] = 12.35 (s, 3H), 7.20 (s, 3H), 7.01 (s, 3H), 6.93 (s, 6H), 6.73 (s, 6H), 6.09 (bs, 6H), 5.91 (s, 3H), 5.04 (s, 3H), 3.39 (s, 6H), 2.79 (s, 6H), 2.09 (s, 18H), 1.73 (s, 9H), 1.38 (s, 54H). 13C NMR [CDCl3] = 166.74, 151.47, 137.74, 131.45, 130.74, 128.80, 127.87, 127.60, 126.80, 126.18, 116.55, 55.67, 34.91, 29.98, 21.15, 20.19. ESI-FTICR-MS: calcd for C99H126N4O9Na 1538.9450; found 1538.9753 [M+H]+. Anal. Calc. for C99H128N4O10: C, 77.52; H, 8.41; N, 3.65. Found C, 77.33; H, 8.75; N, 3.52 Compound 2-4b Using 2.50 g (6.39 mmol) of com pound 1-3b and 0.31 g (2.13 mmol) of Tren afforded 2.10 g (89%) of product. Crystals su itable for X-ray diffraction were grown by a pyridine/methanol diffusion. 1H NMR [CDCl3] = 12.53 (s, 3H), 7.20 (s, 3H), 6.96 (s, 6H), 6.76 (s, 6H), 6.71 (s, 6H), 6.06 (s, 3H), 5.16 (s, 3H), 3.42(bs, 6H), 2.77 (bs, 6H), 2.09 (s, 36H), 1.77 (s, 9H). 13C NMR [DMSO-d6] = 156.75, 150.33, 131.18, 128.84, 127.31, 126.46, 125.11, 123.58, 117.24, 36.47, 20.38, 20.10, 16.73. ESI-TOF-MS: calcd for C81H91N4O9 1263.6730; found 1263.6729 [M+H]+.

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52 General Procedure for the Synthesis of Compound 2-4a-M(III) Com pound 2-4a was dissolved in acetonitrile (30 ml, 80 C) and then treated with the appropriate lanthanide salt. The solution was stirred and afte r five minutes a light yellow precipitate formed. The pure produc t was isolated via filtration. Compound 2-4a-La(III)CH3CN Using 1.25 g (0.82 mmol) of compound 2-4a and 0.48 g (0.82 mmol) of La(CF3SO3)3 afforded 0.46 g (34%) of light yellow product. Crys tals suitable for X-ra y diffraction were grown by a toluene/CH3CN diffusion. 1H NMR [CDCl3] = 8.89 (s, 3H), 8.21 (s, 3H), 7.07 (s, 3H), 6.92 (s, 3H), 6.82 (s, 3H), 6.75 (s, 6H), 6.72 (s, 3H), 6.08 (s, 3H), 4.64 (s, 3H), 4.06 (t, J = 11.4 Hz, 3H), 3.21 (d, J = 11.4 Hz, 3H), 3.03 (d, J =1 2.6 Hz, 3H), 2.58 (t, J = 12.6 Hz, 3H), 2.15 (s, 9H), 2.08 (s, 9H), 2.01 (s, 9H), 1.24 (s, 27H), 1.06(s, 27H). 13C NMR [CD2Cl2] =167.67, 160.86, 152.89, 151.45, 137.39, 137.26, 136.50, 130.13, 129.55, 128.94, 128.58, 128.43, 127.99, 126.95, 125.19, 124.36, 122.96, 116.53, 64.05, 60.48, 36.52, 35.31, 34.92, 30.15, 21.11, 20.77. ESI-FT-ICR-MS: calcd for C99H124O9N4La 1652.8459; found 1652.8457 [M + H]+. Compound 2-4a-La(III)THF Using 1.25 g (0.82 mmol) of com pound 2-4a and 0.48 g (0.82 mmol) of La(CF3SO3)3 afforded 0.46 g (34%) of light yellow crude produ ct. The pure material was obtained from a slow diffusion of CH3CN into THF. 1H NMR [CDCl3] = 8.28 (s, 3H), 8.15 (s, 3H), 7.01 (s, 3H, 6.92 (s, 3H), 6.87 (s, 6H), 6.78 (s, 3H), 6.61 (s, 3H), 5.90 (s, 3H), 4.58 (s, 3H), 4.18 (t, J = 11.4 Hz, 3H), 3.31 (d, J = 11.4 Hz, 3H), 3.09 (d, J = 12.6 Hz, 3H), 2.58 (t, J = 12.6 Hz, 3H), 2.95 (s, 9H), 2.09 (s, 9H), 2.07 (s, 9H), 1.38 (s, 27H), 1.20(s, 27H). 13C NMR [CD2Cl2] =167.67, 160.86, 152.89, 151.45, 137.39, 137.26, 136.50, 130.13, 129.55, 128.94, 128.58, 128.43, 127.99, 126.95, 125.19, 124.36, 122.96, 68.69, 64.05, 60.48, 36.52, 35.31, 34.92, 30.15, 25.36, 21.51, 21.11, 20.77. ESI-FT-ICR-MS: calcd for C99H124O9N4La 1652.8459; found 1652.8457 [M +

PAGE 53

53 H]+. Anal. Calcd for C103H131LaN4O10: C, 71.75; H, 7.66; N, 3.25. Found: C, 71.51; H, 7.68; N, 3.23. Compound 2-4a-Eu(III)CH3CN Using 0.25 g (0.16 mmol) of compound 2-4a and 0.10 g (0.16 mmol) of Eu(III)(CF3SO3)3 afforded 0.09 g (32%) of yellow product. Crystals suitable for X-ray diffraction were grown by a chloroform/CH3CN diffusion. Paramagnetic 1H NMR [CDCl3] = 37.30, 25.21, 15.48, 10.79, 10.07, 9.45, 8.08, 6.11, 5.28, 4.98, 4.31, 3.94, 2.83, 1.30, 1.14, 0.19, -1.64, -2.30, -3.25, -16.93, 34.72. ESI-FT-ICR-MS: calcd for C99H123O9N4EuH 1665.8594; found 1665.8517 [M + H]+. Synthesis of 2-4b*-La(III) A solution of Tren (0.34 g, 2.31 mmol) in metha nol (5 mL) was added to a hot solution of La(NO3)9H2O (0.50 g, 1.15 mmol) in methanol (25 mL, 60 C). The milky solution was stirred at this temperature for two minutes under an ar gon atmosphere. Then, a solution of 2-3b (1.35 g, 3.46 mmol) in methanol was added to the reactio n mixture and stirred. After a few minutes a yellow precipitate formed. The product was isolat ed via filtration and dried to obtain 0.75 g of product. Yield of 60%. Crystals suitable for X-ray diffraction were grown by a CH2Cl2/CH3CN diffusion. 1H NMR [CD2Cl2] = 8.01 (s, 2H), 6.82 (s, 2H), 6.72 (s, 4H), 6.61 (s, 2H), 6.54 (s, 2H), 6.47 (s, 2H), 6.20 (s, 2H), 4.04 (t, J = 14.4 Hz, 2H), 3.35 (d, J = 12.6 Hz, H), 3.25 (s, 6H), 2.92 (t, J = 14.4 Hz, 2H), 2.75 (d, J = 12.6 Hz, 2H ), 2.47 (s, 4H), 2.05 (s, 6H), 2.02 (s, 3H), 2.01 (s, 3H). 13C NMR [CD2Cl2] =169.18, 150.43, 149.83, 134.82, 134.38, 133.44, 131.28, 130.28, 130.14, 129.76, 129.76, 128.57, 127.55, 126.32, 123.81, 122.01, 60,43, 59.35, 40.05, 37.53, 21.09, 21.01, 20.71, 16.51, 16.40. ESI-FT-ICR-MS: calcd for C56H63O6N4La 1026.39; found 1027.3956 [M + H]+.

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54 General Procedure for the Synthesis of Compounds 2-5 Com pound 2-3 was added to 250 mL of absolute ethanol. The resulting solution was brought to a reflux. A solution of 1,1,1-Tris(aminoethyl)methane (Tame) (5 ml of absolute ethanol) was added to the refluxing ethanol mixture, which immediately turned bright yellow. A yellow precipitate formed within an hour, but the mixture continued to reflux for a full 12 hours. The pure product was collected by filtration and dried. Compound 2-5a Using 12.13 g (25.64 mmol) of compound 2-3a a nd 1.0 g (8.54 mm ol) of Tame afforded 11.20 g (88%) of product. 1H NMR [THF-d4] = 13.29 (s, 3H), 8.41 (s, 3H), 7.00 (s, 3H), 6.96 (s, 6H), 6.79 (s, 3H), 6.51 (s, 6H), 6.19 (s, 3H), 6.15(s, 3H), 4.70 (s, 3H), 3.62 (s, 6H), 2.16 (s, 9H), 2.11 (s, 18H), 1.36 (s, 54H), 1.10 (s, 3H). 13C NMR [pyridine-d5] = 166.85, 157.42, 151.89, 133.90, 132.62, 131.45, 130.27, 128.49, 128.26, 126.93, 126.21, 118.06, 64.17, 39.50, 34.81, 30.05, 20.97, 20.20, 19.92. ESI-FT-ICR-MS: calcd for C98H123N3O9 1487.9415; found 1487.9147 [M]+. Compound 2-5b Using 2.50 g (6.39 mmol) of com pound 2-3b a nd 0.25 g (2.13 mmol) of Tame afforded 2.24 g (91%) of product. Crystals suitable fo r X-ray diffraction were grown by a THF/MeOH diffusion. 1H NMR [d6-DMSO] = 13.35 (s, 3H), 8.46 (s, 3H), 7.80 (bs, 6H), 7.03 (s, 3H), 6.71 (s, 6H), 6.63 (s, 3H), 6.44 (s, 3H), 6.31(s, 6H), 3.52 (s, 6H), 2.12 (s, 9H), 2.09 (s, 18H), 2.05 (s, 18H), 0.98(s, 3H). 13C NMR [d6-DMSO] = 156.30, 150.29, 131.89, 131.20, 129.01, 127.37, 126.68, 125.91, 123.75, 117.58, 56.04, 36.30, 20.58, 20.34, 18.57, 16.72. ESI-TOF-MS: calcd for C80H87N3O9Na 1256.4335; found 1256.6413 [M + Na]+.

PAGE 55

55 Synthesis of 2-5b-Co(III) A portion of 2.00 g (1.72 mm ol) of 2-5b was dissolved in a so lution of ethyl acetate (10 ml) and THF (40ml). A solution of cobalt (II) acetate tetrahydrat e (0.43 g, 1.73 mmol) in methanol (10mL) was added to the yellow slurr y. A hydrogen peroxide so lution (5 mL of 3%) was added and the mixture was boiled until the so lid dissolved. The subsequent solution was dark brown. Water was added to the reaction mixture and th e product was extracted with methylene chloride (3 X 100 ml). The extracts were combined and dried over anhydrous sodium sulfate. The volume was reduced to 10 mL, and the mixture was loaded onto a short plug of neutral alumina and eluted with CH2Cl2. The solvent was removed in vacuo to give 1.02 g pure brown product in a yield of 46%. Crystals su itable for x-ray diffr action were grown by a CHCl3/methanol diffusion. 1H NMR [CDCl3] = 7.15 (s, 3H), 6.72 (d, J = 2.7 Hz, 3H), 6.68 (s, 3H), 6.65 (s, 3H), 6.51 (s, 3H), 6.45 (s, 3H), 6.41 (s 3H), 6.16(s, 6H), 5.82 (s, 3H), 3.71 (d, J = 12.3 Hz, 3H), 2.89 (d, J = 12.9 Hz, 3H), 2.12 (s, 18H), 2.05 (s, 9H), 1.97 (s, 9H), 1.63 (s, 9H), 1.12(s, 3H). 13C NMR [CDCl3] = 166.84, 161.18, 151.00, 150.01, 137.17, 134.94, 132.38, 130.41, 129.76, 128.98, 128.02, 127.41, 127.21, 126.40, 125.08, 122.84, 117.41, 68.69, 65.58, 37.62, 27.98, 21.11, 20.97, 20.75, 16.61, 15.69. Anal. Calcd for (2-5b-Co(III)2MeOH) C82H92CoN3O11: C, 72.71; H, 6.85; N, 3.10. Found: C, 72.65; H, 6.52; N, 3.13. ESI-TOF-MS: calcd for C80H84N3O9CoNa 1312.5432; found 1312.5409 [M + Na]+. Synthesis of 2-5b-Fe(III) 1.00g (0.88 mmol) of 2-5b was dissolved in a solution of 1:1 CH3CN/CHCl3 (30 mL). Iron (III) perchlorate (0.44 g, 0.97 mmol) wa s added to the yellow solution and allowed to stir for 15 minutes. The subsequent solution was dark purple. The solution was reduced in vacuo, the residue was dissolved in CH2Cl2, and the mixture was loaded onto a short plug of neutral alumina, which was eluted with CH2Cl2. The solvent was removed in vacuo to give 0.79 g pure

PAGE 56

56 purple product in a yield of 76%. Crystals su itable for X-ray diffraction were grown by a CH2Cl2/pentane diffusion. Anal. Calcd for (2-5b-Fe(III)Pentane) C85H96FeN3O9: C, 75.00; H, 7.12; N, 3.09. Found: C, 74.63; H, 7.30; N, 3.05. ESI-TOF-MS: calcd for C80H84N3O9FeNa 1309.5465; found 1309.5465 [M + Na]+. Figure 2-1. Schematic drawing of the resi dues in the ClC chloride channels of E. coli that are involved in the binding of a chloride anion. Figure 2-2. Schematic drawing of the general synt hesis of the Schiff base ligand and Schiff base metal complexes. (i) refluxing absolute ethanol, 24 hours; (ii) refluxing toluene, 24 hours.

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57 Figure 2-3. Illustration of the s ynthetic route used to prepare the aldehyde derivative of the triphenoxymethane platform with different al kyl substituents at the 3 and 5 positions. R = t b u HO OH HO R R H R Figure 2-4. Illustration of th e triphenoxymethane platform in the all up conformation.

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58 Figure 2-5. Illustration of Sc hiff base reaction of Tren with aldehyde derivative of the triphenoxymethane platform. (i) re fluxing absolute ethanol, 12 hours. Figure 2-6. Illustration of the synthetic route used to produce 2-4a-M(III). (i) La(III)(CF3SO3)3 or Eu(III)(CF3SO3)3, boiling acetonitrile, 5 minutes.

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59 Figure 2-7. Solid-state st ructure of 2-4a-La(III) CH3CN with a coordinate d acetonitrile on the La(III) metal center (30% probability; carbon at oms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. Figure 2-8. Solid-state struct ure of 2-4a-La(III)THF with a coordinated THF on the La(III) metal center (30% probability; carbon atom s depicted with arbitrary radii). The hydrogen atoms are omitted for clarity.

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60 Figure 2-9. Diagram of the solid-s tate structure of 2-4a-Eu(III) CH3CN with a coordinated acetonitrile on the Eu(III) metal center (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. R OH R R OH R R HO H O N NH2 H2N NH2 + 3 2-3: R= t -butyl or methyl+ La(III) salt La O HO HO R R R R N N 32-4-La(III ) R= tbutyl or methyl Figure 2-10. Depiction of an additional s ynthetic route used to produce 2-4-La(III).

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61 Figure 2-11. Diagram of the soli d state structure of ligand 2-4b*-La(III) (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. M O HO HO N N Cl O O 3 Figure 2-12. Schematic diagram of the propos ed binding of perchlor ate to 2-4a-M(III). For clarity the diagram depicts one third of the metal complex and perchlorate anion. The t -butyl groups and the hydrogen atoms are also omitted for clarity.

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62 Figure 2-13. Depiction of the 1H NMR spectrum of 2-4-La(III)CH3CN (top) and the 1H NMR spectrum of 2-4-La(III)CH3CN treated with less th an one equivalent of tetrabutylammonium fluoride (bottom) in CDCl3. The indicates the 1H NMR signals associated with compound 2-4a.

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63 Figure 2-14. Synthetic scheme for the formation of triphenoxymethane sa lens 2-5a and 2-5b. (i) refluxing absolute ethanol, 12 hours. Figure 2-15. The solid-state structure of ligand 2-5b (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity.

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64 N N OH HO HO HO HO HO N HO OH OH M O N HO OH 3 i 2-5b 2-5b-Co(III) 2-5b-Fe(III) Figure 2-16. Synthetic scheme for the formation of 2-5b-Co(III) ((i) Co(II)ace tate tetrahydrate, 5% H2O2, 70 C, THF/ethyl acetate, 5 minutes) and 2-5-Fe(III) ((i) Fe(III) perchlorate, CH3CN3/CHCl3, 15 minutes).

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65 Figure 2-17. The solid-state st ructure of complex 2-5b-Co(III). The hydrogen atoms are omitted for clarity (30% probability; carbon atom s depicted with arbitrary radii).

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66 Figure 2-18. Diagram of the solidstate structure of ligand 2-5b-Fe(III) (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity.

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67 Figure 2-19. Diagram of the solid-st ate structure of ligand 2-5b-Co(III)-H2O with water bound in the phenolic pocket (30% probability; car bon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. Figure 2-20. The simplified structure around the cen tral metal ion of 2-4a-M(III). The atoms remote from the central metal ion as well as the hydrogen atoms were omitted for clarity.

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68 Figure 2-21. The simplified structure around the cen tral metal ion of 2-5b-M(III). The atoms remote from the central metal ion as well as the hydrogen atoms were omitted for clarity.

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69 Table 2-1. Distances ( di) between planes (Fi) and the twist angles ( wi) in each portion. d1 () d2 () d3 () w1 ( ) w2 ( ) w3 ( ) w1 + w2 +w3 or w1 + w2 ( ) 2-4a-La(III)CH3CN 0.969 1.265 2.110 -17.3 18.8 49.3 50.8 2-4a-La(III)THF 1.025 1.202 1.906 -15.4 20.8 53.2 58.6 2-4a-Eu(III)CH3CN 1.074 1.193 2.051 14.6 -21.6 -52.9 -59.9 2-5b-Co(III) 1.395 2.242 18.3 62.7 81.0 2-5b-Fe(III) 0.824 2.428 17.6 47.6 65.2 Table 2-2. Crystallographic data for compounds 2-4a-La(III)CH3CN, 2-4a-La(III)THF, 2-4aEu(III)CH3CN, and 2-4b*-La(III). 2-4a-La(III) 0.5 CH3CN-0.5 CHCl32-4a-La(III) 2 THF 2-4a-Eu(III) CH3CN-CHCl3 2-4b*-La(III) CH3CN Formula Crystal System Space Group Z a () b () c () ( ) ( ) ( ) Vc (3) Uniq. data coll./obs. R1[ I 2 (I)data] wR2[ I 2 (I)data] C102.5H129Cl1.5N5.5O9La Trigonal R-3 6 21.857(3) 21.857(3) 37.293 (4) 90.00 90.00 120.00 15429(3) 6735/2738 0.0822 0.0939 C111H147N4O12La Triclinic P-1 2 14.2877(14) 16.9381(16) 23.436(3) 90.961(2) 91.479(2) 111.004(2) 5948.0(10) 26820/21358 0.0269 0.0588 C104H130Cl3N6O9La Trigonal R-3 6 22.14487(7) 22.1448(7) 37.030(2) 90.00 90.00 120.00 15726.6(12) 6159/3630 0.0608 0.0607 C60H69N9O7La Monoclinic P2(1)/n 4 15.0422(10) 16.6240(11) 25.33.17(18) 90.00 105.885(2) 90.00 6092.6(7) 14279/6100 0.1110 0.1944

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70 Table 2-3. Crystallographic data for com pounds 2-5b, 2-5b-Co(III), 2-5b-Fe(III), and 2-5bCo(III)-H2O. 2-5b3THF 2-5bCo(III) 3.5MeOHCHCl3 2-5bFe(III)3CHCl3 2-5bCo(III) 2.5C3H6OH2O Formula Crystal System Space Group Z a () b () c () ( ) ( ) ( ) Vc (3) Uniq. data coll./obs. R1[ I 2 (I)data] wR2[ I 2 (I)data] C92H101N3O12 Trigonal R-3 6 22.3667(10) 22.3667(10) 26.467(2) 90.00 90.00 120.00 11466.8(13) 5216/2830 0.0561 0.0622 C84.5H99Cl3N3O12.5Co Triclinic P-1 2 12.674(3) 14.588(3) 21.556(5) 93.897(40 95.114(4) 92.243(4) 3956.3(16) 17343/7557 0.0549 0.1511 C83H87Cl3N3O9Fe Triclinic P-1 2 12.496(12) 15.7792(5) 19.4898(19) 84.866(2) 84.405(2) 84.514(2) 3794.7(6) 17054/12374 0.0234 0.0505 C87.5H101N3O12.5Co Monoclinic P2(1)/c 4 13.8613(11) 21.9125(17) 27.283(2) 90.00 103.129(2) 90.00 8070.3(11) 12658/4746 0.1302 0.2084

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71 CHAPTER 3 ANION BINDING STUDIES WITH METAL SALEN COMPLEXES INCORPORATING UREA M OIETIES Introduction The binding of anions through the hydrogen bonding interactions of NH groups has been widely studied. A major portion of synthetic receptors is polyamine based and includes receptors containing guanidinium salts and oligo pyrroles. Neutral ani on binding receptors that are urea based are another popular binding motif. The urea moiety contains two hydrogenbonding donors that point in the same direction an d tend to bind Y-shaped anions such as carboxylates, nitrates, and phosphates. However, the binding ab ility of urea-based receptors is not limited to Y-shaped ions. Many receptors have been produced that bind fluoride, chloride, bromide, and many others. Other major advantag es to urea-based receptors are synthetic ease and versatility. Urea subunits can be used to link together smaller molecular subunits allowing the formation of acyclic, cyclic, and metal templated systems.63 Early in the study of urea-based receptors, solid-state studie s performed by Etter and coworkers64 illustrated the hydrogen bond me diated recognition properties of the urea functionality (Figure 3-1). The solid-state structure of the complex wa s important because it provided evidence that urea groups could be used to bind the more complex oxy-anions. Many receptors followed which included multiple urea groups conn ected by rigid aromatic spacers. The choice of linker helped tune the selectivity of the receptor. For example, receptor 3-1 was selective for dihydrogen phosphate65, 66 while receptor 3-2 preferred carboxylate anions67, 68 (Figure 3-2). Each receptors preference was attributed to th e specific geometry and directionality of the hydrogen-bonding interaction pr ovided by the receptor. The affinity for various oxy anions continued to improve as receptors were produced that incorporated three urea s ubunits (Figure 3-3).

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72 Urea receptors 3-3 and 3-4 bot h selectively bind phosphate;69-71 however, compound 3-4 proved to be a phosphate anion receptor with a binding cons tant one order of magnitude larger than that measured for compound 3-3 and phosphate. The finding was attributed to the more suitable cavity produced by the tris -aminoethyl spacer. The library of urea-based receptors continued to grow to include cyclic systems. The macrocycles include two to four urea subunits linked by aromatic spacers and/or alkyl groups (Figure 3-4). Macrocycles 3-5 and 3-6, reported by Reinhoudt and co-workers,72 both bind dihydrogen phosphate, but the affinity of receptor 3-6 for the anion is less th an that of receptor 35. The findings suggests that 3-6 lacks the flexibili ty that would allow the macrocycle to better accommodate the large anion. In addition to acyclic and cyclic receptors, urea receptors that contain metal ions have also been reported. The metal can be used as a Lewis acidic anion-binding site, as an organizational element in the structural framewor k, or as both. Receptor 3-7 (Figure 3-5) uses Pt2+ to bind four urea units in a s quare planar geometry. The Pt (II) complex was not selective for one anion, but could bind ch loride as well as sulfate.73 The behavior of 3-7 was explained by solid-state studies, which showed that the receptor could adopt two different conformations. The 1,2-alternate conformation stabilized chloride, while the all up conformation formed a cone, which was ideal for encapsulating sulfate. Recently, the design and utility of lumines cent and colorimetric molecules for anion recognition and sensing has become an active field of research within the ar ea of supramolecular chemistry. 74-76 The molecules used as sensors gene rally have a receptor component and a signaling unit that is capable of translating the analyte-binding induced changes into an output signal. This is generally probed either by spectroscopic techniques or by visual detection of the

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73 targeted analyte through a change in color. Among various receptors, hydrogen bond donor urea functionalities, such as the recep tors seen in Figure 3-6, have been widely used for selective binding of anions including fluoride, CH3COO-, and H2PO4 -.77, 78 Solutions containing either sensor produced color changes, which could be detected by the naked eye upon the addition of F-, AcO-, and H2PO4 -. The receptors were selective for fluoride over other halides and for AcO-, and H2PO4 over other oxy anions teste d. For both sensors the dramatic color changes were attributed to changes in the inte rnal charge transfer excited stat es induced by the binding event. Work done in the Scott group by Dr. Eric Libra79 demonstrated further use of metal ions as organizational elements in urea based receptor s. Tripodal amines, Tren and Tame, and urea aldehyde 3-10 (Figure 3-8) were used to synt hesize receptors containing three urea subunits (Figure 3-7). The urea salen ligands produced were used to chelate Lu(III) (3-8) and Co(III) (39) ions in order to produce well-defined bindi ng pockets. The binding pockets contained six NH donors aligned in the same directio n. Receptor 3-9 was found to bind Fas well as Cl-, while receptor 3-8 selectively binds Cl-. The differences in the binding ability of the receptors were attributed to variations in th e binding cavity, which were affect ed by the size of the metal ion used to form the cavity. Further work done by Dr. Eric Libra, showed th at the size of the metal ion could also play a role in determining the affinity of the receptors. Urea salen 3-11 (Figure 3-8), produced by a simple condensation of urea alde hyde 3-10 and 1,2-diamino-cyclohex ane, was treated with Ni(II) and Pd(II) salts to produce complexes 3-11-Ni(II) and 3-11-Pd(II). Both complexes were found to bind F-, Cl-, and Br-, but receptor 3-11-Pd(II) ha d a higher affinity for Cland Brthan receptor 3-11-Ni(II). The larger Pd (II) metal center crea ted a larger binding pocket, which was better suited for the larger Cland Branions.

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74 The work done in the Scott group has shown that tunable urea based receptors can be produced through Schiff base reactio ns and metal chelation. The size of the binding pocket of the above mentioned complexes were restricted to binding halides. Therefore, we envision using the same approach to produce larger or more complex urea-based receptors using urea aldehyde 3-10 and urea dialdehyde 3-14, which could then be used to bind larger oxy anions or biologically relevant substrates. The synthesis of the urea ba sed ligand, their metal chelation, and the resulting receptors interaction w ith the substrates are reported herein. Results and Discussion Reactions with Urea Aldehyde 3-10 Since the Schiff base reaction could be su ccessfully employed to produce pure urea-based receptors with two and three subunits, it was thought that the same approach could be applied to produce mixed salens with O-H as well as N-H d onors. Previous research efforts by the Scott group has produced a bifunctional receptor synthesi zed in a stepwise procedure incorporating one triphenoxymethane subunit and one urea subunit.79 The functionalities were linked together through a salen backbone, which was used to chelate a Ni(II) meta l ion (Figure 3-9). The chelation of the Ni(II) i on produced a binding pocket consisting of two O-H and two N-H donors. The four hydrogen-bonding donors were used to bind Fand ClContinuing with the goal to synthesize recept ors with the ability to encapsulate larger anions and substrates, attempts were made to produce larger multi-functional receptors. Previously reported complex 2-4b*-La(III) (Figure 2-11) was an ideal complex that could be used to accomplish this goal. Complex 2-4b*-La(III) contains two phenol subunits and one partially unreacted nitrogen. Under the correct conditions this nitrogen could react with an aldehyde allowing the incorporation of an additional binding subunit. All attempts made to

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75 incorporate an additional tri phenoxymethane were unsuccessful; however, the reaction could be favored with a different aldehyde such as compound 3-10. A boiling solution of 2-4b*-La(III) was treated with a few dr ops of triethylamine and urea aldehyde 3-10 was added to the so lution resulting in the formation of the complex 3-13-La(III) (Figure 3-10). Complex 3-13La(III) was analyzed via 1H NMR spectroscopy. The addition of the urea subunit was immediatel y apparent when observing the 1H NMR spectrum. A new imine proton appeared at 8.51 ppm as we ll as a variety of signals in the aromatic region, which were accompanied with significant change s in the alkyl region. In the 1H NMR spectrum of 2-4b*La(III), the signals in the region of 4.5-2.5 ppm we re assigned to the protons on the carbons in the Tren subunit. The 1H NMR spectrum shows five peaks in this region: two doublets, two triplets, and singlet. Upon th e production of complex 3-13-La (III), the number of signals increases to six. The single t at 2.75 ppm, which is attri buted to the protons on the CH2CH2 linker of Tren that were not i nvolved in the metal chelation, di sappears and these protons have two new signals at 3.69 ppm and 3.01 ppm. The addition of the urea subunit also causes the appearance of a t -butyl signal at 1.29 ppm. Mixed metal salen 3-13-La(III) produced suitable single crystals fo r solid-state studies from a slow diffusion of pentane in to toluene. The solid state st ructure of 3-13-La (III) (Figure 311) shows an eight coordinate La(III) complex. The metal is bound to the four nitrogens of the Tren subunit, three phenol oxygens as well as an oxygen of a coordinated water molecule. Unlike the coordinated THF or CH3CN molecules in the 2-4a-La(III) complexes, this water (La(1) O(9) 2.699(4) ) molecule does not point toward the binding pocket produced. The La(1) O(1/2/3) distances measure 2.309(3) 2.336(3), and 2.411(3) while the La(1) N(1/2/3/4) distances measur e 2.780(3) 2.741(4) 2.683(4) and 2.649(3) The

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76 longest La-O bond is formed between the metal and the oxygen on the urea subunit (La(1) O(3)) and the longest La-N bond is formed between the metal and the apical nitrogen (La(1) N(1)). Comparing the La-O and La-N bonds of 2-4b*-La(III) and 3-13-La(III), the data shows these bonds are nor significantly affect ed by the addition of urea-based subunit. There are considerable intramolecular hydrogen bondi ng interactions in complex 3-13-La(III). Two phenols in the binding pocket intera ct with the phenolate oxygens with O O distances of 3.075 The remaining phenols (O(5) and O(8) ) form hydrogen bonds to the nitrogens (N(5) and N(6))of the urea subunit with N O distances of 3.205 and 3.072 respectively. The average C C distance between the three binding arms is smaller than that of both 2-4a-La(III) complexes, which measures 5.63 Anion Binding Studies of 3-13-La(III) Because of the com plex nature of the 1H NMR spectrum of 3-13-La (III) it was difficult to definitively identify the O-H and N-H signals. T hus, all initial binding studies were carried out using UV-vis spectroscopy. The UV-vis absorb ance of 3-13-La(III) did not change upon the addition of the tetrabutylammonium salts of F-, Cl-, Br-, NO3 -, and PO4 3to the solution, but the absorbance of 3-13-La(III) significantly red sh ifted upon the addition of hydrogen sulfate and perchlorate. Titrations were performed by sy stematically adding measured amounts of a 2M solution of tetrabutylammonium hydrogen sulfate in dichloromethane. At zero equivalents of the anion the maximum absorbance was 378 nm. Upon the addition of hydrogen sulfate up to one equivalent of the anion, two isobestic points formed at 345 nm and 406 nm and the maximum absorbance shifted to 432 nm. The data was analyzed in order to determine the affinity of 3-13-La(III) for HSO4 -. When the data was plotted the curve was sigmoidal as opposed to an expected exponential curve, which

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77 suggests that some other process wa s occurring during the experiment. 1H NMR spectroscopy was used to confirm that complex 3-13-La(III) was not binding hydrogen sulfate but was causing the complex to demetallate and rearrange. The titration experiments with the complex and hydrogen sulfate show the steady growth of th e signals associated with salen 2-4b via 1H NMR spectroscopy. Lastly, th e absorbance of the solution cont aining one equivalent of hydrogen sulfate and the complex is exactly the same as a solution of 2-4b. 1H NMR experiments of 3-13La(III) and perchlorate also show the growth of the signals a ttributed to salen 2-4b, which suggests that mixed salen 3-13-La(III) is not a good candidate for anion binding. Reactions with Urea Dialdehyde 3-14 In order to study the anion binding ability of larger urea-based anion receptors, urea dialdehyde 3-14 (Figure 3-12) wa s developed and synthesized by for mer Scott group member Melanie Veige. The urea subunit was carefully designed to ensure that the compound would be a good candidate for producing large macrocyclic urea based receptors. First, two aldehyde moieties were needed, which would allow Schiff ba se reactions to occur at both ends of the subunit. Second, the subunit had to be rigid and planar to minimize the formation of polymers as opposed to macrocycles. Third, the subunit ha d to contain two N-H donors for anion binding purposes as well as two O-H donors, which would be used to chelate metal ions or as a hydrogen-bond donor for anion binding. Finally, t-butyl groups were included in the subunit to increase the solubility of the form ed macrocycles in organic solvents. Reactions of 3-14 with diamines Following the general approach for producing sa lens, a solution contai ning two equivalents of dialdehyde 3-14 in refluxing absolute etha nol was treated with two equivalents of 1,2Phenylenediam ine, 4,5-dimethyl-1,2-Phenylenediamine, or Ethylenediamine (Figure 3-13). The reaction conditions produced bright orange or yellow solid s that were analyzed via 1H NMR

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78 spectroscopy. The spectra of each solid showed only seven proton signals, which would be expected upon the formation of the macrocycle because they are highly symmetric. Thus, under the reaction conditions the forma tion of macrocycles 3-15a/b/c was favored over the formation of a polymer. Because of the poor solubility of compounds 3-15a/b/c no efforts were made to produce single crystals of each urea-bas ed macrocycle for solid-state studies. Anion binding studies with urea-based macrocycles 3-15a/b/c Because of the sim ple nature of the 1H NMR spectra of 3-15a/b/c the O-H and N-H signals were easily identified. As a result, all in itial binding studies were carried out using 1H NMR spectroscopy. Unfortunately, macrocycle s 3-15a/b/c were soluble only in d6-DMSO, which is not an ideal solvent to test anion binding since the solvent competes for the anion. Of the three macrocycles, 3-15a was the only macrocycle th at was completely soluble and remained in solution over time. Therefore, 3-15a alone wa s tested for its anion binding ability. The tetrabutylammonium salts of select oxy anions (NO3 -, HSO4 -, ClO4 -) were tested as well as the halides Br-, Cl-, and F. The 1H NMR spectrum of the receptor did not change in any way upon the addition of all the anions except F-. Upon the addition of even small amount of fluoride to the solution of 3-15a, a pr ecipitate formed and the 1H NMR signals of the receptor shifted and broadened significantly. Th e addition of fluoride appears to f acilitate the forma tion of a polymer and the data suggests that macrocycle 3-15a is not an ideal anion receptor. Metallation of macro cycles 3-15a/b /c Since macrocycles 3-15a/b/c did not disp lay anion-binding abili ties on their own, the macrocycles could be good candidates for producing urea based supramolecular boxes for anion binding purposes. Examples of supramolecular boxes produced with Zn( II)-Salphen complexes were reported by Reek and co-workers80 (Figure 3-14).

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79 Complex 3-16 is ideal for producing higher-order molecular structures because the complex is rigid, planar, and can utilize pyridine-Zn coor dination motifs. Supramolecular boxes (3-16)2 were formed in acetone when 3-16 was trea ted with 1,2-bis(4-pyridyl)ethane, 1,4-bis(4pyridyl)benzene, or 1,2-bis(4-pyridyl)ethylene. Upon the chelation of Zn (II) metal ions in complexes 3-15a/b/c, the resulting metal comple x would also be an ideal subunit for producing supramolecular box assemblies. Metallation of 3-15a/b/c was accomplishe d by treating a refluxing THF solution containing the macrocycle and a few drops of triethylamine with a portion of Zn(II) Acetate. A solid did not form from the reac tion mixture, so the solution was allowed to reflux for 12 hours. A solid was isolated upon the removal of the solvent, which was analyzed via 1H NMR spectroscopy. Once the metallation had taken place, the only expected change in the spectra would be the disappearance of the O-H signa ls (13.58 ppm for 3-15a, 13.68 ppm for 3-15b, and 13.91 ppm for 3-15c), but the 1H NMR spectra (Figure 3-15) of th e resulting products were more complicated. The 1H NMR shows a clean product, but instead of the expected four peaks in the region of 9.0-6.0 ppm there are 17 peaks, in the region 2.5-2.0 ppm there are two signals instead of one signal, and in the regi on between 1.5-1.0 ppm four signals as opposed to one signal. The data suggest that the metallation involves multiple macrocycles. Solid-state studies of the product from the reaction of 3-15a and Zn(II) Acetate confirmed that the reaction conditions produced complexes with two ligands and 4 Zn atoms (Figure 3-16). Single crystals of (3-15a-Zn(II))2 were obtained from a slow diffusi on of pentane into THF. The solid-state structure (Fig ure 3-17) shows two dist inct metal centers. Zn1 and Zn2 are sixcoordinate, binding two nitrogen s and two oxygens of one macroc ycle, an oxygen in the adjacent macrocycle (Zn O 2.009 and 2.129 ) and the oxygen of a THF molecule (Zn O

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80 2.339(2) and 2.330(2) ). Zn3 and Zn4 are five-coordinate, bindi ng two nitrogens and two oxygens of one macrocycle plus an additiona l oxygen from the carbonyl on the adjacent macrocycle (Zn(3/4) O(8/2) 2.0768(19) and 2.095(2) ). All non-bridging Zn-O and Zn-N bonds are similar to those reported for similar Zn(II) salen complexes with phenyl backbones.81 The configuration of the complex produced a circular cavity with eight N-H donors pointed toward each other. Each macrocycle has one water molecule that is hydrogen bound between the urea subunits with average N O distances of 3.199 and 3.241 Complexes (3-15a/b/c-Zn(II))2 were treated with pyridine in hopes of isolating a single macrocycle with two metal centers. 1H NMR spectra of solutions containing (3-15a/b/c-Zn(II))2 and small amounts of pyridine show significantly fewer signals, confirming that in the presence of pyridine the complex consisting of two ligands and four Zn(II) atoms is no longer favored. Single crystals of 3-15a-Zn(II) py were obtained from a slow diffu sion of pentane into THF. The solid-state structure of 3-15a-Zn(II) py (Figure 3-18) shows two five coordinate Zn (II) centers with Zn O bonds of 1.9529(6) and 1.958(7) and Zn N bond lengths of 2.111(9) 2.144(9) and 2.009(9) (N5). Th ese bond lengths are similar to those of previously published Zn(II) salen structures 81 as well as those in comp lex 3-16. The rigidity of the phenyl amine used to produce the ligand as we ll and the rigidity of the urea subunits forces the Zn(II) atoms to chelate to the same side of the macrocycle, which is essential for producing supramolecular boxes. The chelation of the metal ions distorts the macrocycle by 33.5 which is a larger dihedral angle than th e one produced in complex (3-16)2 formed with 4-4-bipyridine (20.40(6) ). The relative potential binding pocket, th e distance between the carbonyl carbons, is measure to be 7.509

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81 Reactions of (3-15a-Zn(II))2 with bipyridine ligands Due to poor solubility, co mplexes (3-15b/c-Zn(II))2 was not tested for its ability to produce supramolecular boxes, but complex (3-15a-Zn(II))2 was tested by adding small amounts of 4, 4bipyridine, 1,2-bis(4-pyridyl)ethane, or 1,2-bis(4-pyridyl)ethylene to acetone-d6 solutions containing (3-15a-Zn(II))2. The 1H NMR spectra of the solutions were monitored for the dissociation of (3-15a-Zn(II))2, which was indicated by the appearance of the simple 1H NMR spectrum similar to that of compound 3-15a-Zn(II)py. All three Lewis bases were able to dissociate (3-15a-Zn(II))2, but only in acetone. The dissociati on did not always occur in other solvents that were tested. As a result, crystall izations were set up consisting of (3-15a-Zn(II))2 and the desired bipyridine ligand in acetone in hopes of crysta llizing 2:2 box assemblies. Single crystals were grown and solid-state structures were determined for mixtures containing (3-15a-Zn(II))2 and all three bipyridine ligands. The solid-state structure of (3-15aZn(II))2 and 1,2-bis(4-pyridyl)ethane, wh ich were grown from a CHCl3-Acetone/Pentane diffusion, shows the structure of 3-15a-Zn(II) (bipy-CH2CH2) and not that of a 2:2 box assembly. The ethane linker betw een the two pyridines appears to be too flexible and under the crystallization conditions prefer entially binds to the Zn(II) atom s of the same macrocycle as opposed to between two different macrocycles. All other solvent combinations tested did not produce X-ray quality crystals. In anticipation of preventi ng the binding mode preferred by the 1,2-bis(4-pyridyl)ethane ligand, a bipyridine subunit with a rigid spacer was selected. Consequently, crystallizations with (3-15a-Zn(II))2 and1,2-bis(4-pyridyl)ethylene were se t up and the solid-state structure was obtained from a THF-MeOH-Acetone/CH3CN diffusion. The rigid linker did prevent the bipyridine ligand from binding to the Z(II) atom s on the same macrocycle. However, the

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82 conditions under which the crysta ls were grown did not produce a 2:2 box either (Figure 3-19). Instead, an infinite solid was pr oduced by a stair-step linkage of one metallated macrocycle to the next through one 1,2-bis(4-pyri dyl)ethylene unit. All other c onditions did not produce single crystals. Single crystals were obtained from a slow diffusion of CH3CN into a THF-MeOHAcetone solution containing (3-15a-Zn(II))2 and 4-4-bipyridine. Th e solid-state structure did not show the formation of 2:2 box assemblies unde r the crystallization co nditions (Figure 3-20). Like the solid produced from the crystallization of (3-15a-Zn(II))2 and 1,2-bis(4pyridyl)ethylene, the crystalliza tion conditions of (3-15a-Zn(II))2 and 4,4-bipyridine produced and infinite solid with a sta ir-step linkage of one metallate d macrocycle to the next through one 4,4-bipyridine unit. The presence of 3-15a-Zn(II) py units flanking each side of the stairstep structure was not expected, but upon the examination of the (3-15a-Zn(II))2 solid used in the crystallization it was discovered that the solid at one point had been exposed to pyridine. All other attempts to produce single crystals without the presence of pyridine were unsuccessful. Because discrete box assemblies were not produce d, anion-binding studies were not performed. Reactions of 3-14 with Tris-Amines Dialdehyde 3-14 could also be used in Schiff base reac tions to produce urea-based cryptates with hydrogen-bonding cavities suitable for substrate binding. Em ploying a metal template strategy and using a tripodal amine, Tr en, dialdehyde 3-17, and a variety of metal (III) ions, Kanesato and co-workers82 were able to isolate and crysta llize dinuclear lanthanide(III) and yttrium(III) cryptates (Figure 3-21). The structural characteristics of 3-17 as well as the use of the metal ion were the key to producing the crypt ates as opposed to polymers. Similar cryptates with urea moieties could also be used to produce using this synthetic strategy.

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83 In order to quickly analyze the resulting product via 1H NMR spectroscopy, Lu(III) Triflate were chosen as the metal templates for the urea-based cryptates. Under the reaction conditions used by Kanestato et al.,82 solids began to instantly form upon the drop-wise addition of a solution of dialdehyde 3-14 to another solution containing the metal salt and tripodal amine. The solids were collected via filtra tion and found to be insoluble in all organic solvents and bases present in the laboratory. Previous examples of metall ated phenol-based cryptates have been produced using a different template strategy.83 During the reaction, the dialdehyde was treated with a Group 1 or Group 2 cation before the tris -amine, Tren, was added to the reaction mixture. The Group 1 cryptates produced were then used in transmetallation reactions. Employing this strategy, attempts were made to produce the cryptates by using NaClO4 as a template, dialdehyde 3-14, and Tren. Unfortunately, under varying conditi ons along with the Group 1 cation the reactions produced insoluble solids as well. Abandoning template-based synthesis, focus was placed on limiting the flexibility of the tris -amine as a means to reduce the possibility of polymer formation. Two amines were chosen; the tripodal amine Tame and the tris -amine cis, cis-1,3,5-triaminocyclohexane known as Tach (Figure 3-22). Tame, with a methlyene as opposed to an ethylene linker, would have decreased flexibility but still have the ability to bind tran sition metals. Tach, with amines directly bound to a cyclohexane ring, would be even less flexible than Tame. As a resu lt, the possibility for polymer formation should also decrease when Tach is used for cryptate production not only because of its decreased flexibility, but also beca use the amines are pre-organized on one side of the cyclohexane ring

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84 For the reactions with Tame, dialdehyde 3-14 wa s dissolved in a variety of solvents and treated drop-wise with a dilute solution of Tame. All of th e reaction conditions attempted produced an insoluble solid. Pr oducing even simple salens with Tach is different from producing salens with Tame or Tren. Salens made with Tame or Tren are typically produced in absolute ethanol because the imine bonds produced during the reaction are susceptible to hydrolysis. Based on reports of previous salens made with Tach, the formation of the imine bonds are favored in an ether solu tion containing NaOH and water.84 Before attempts were made to produce the cryptate, the re action conditions were tested on the urea aldehyde 3-10. The desired salen was produced under the reaction co nditions containing ether, NaOH, and water, while reactions in ether alone or absolute ethanol produced insol uble solids. Unfortunately, the conditions, which favored the formation of the urea-based Tach salen, produced an insoluble solid when used in the attempt to make the Tach cryptate. The products isolated from the other reactions suggest that the flexibility of the tris amine should not be the only consideration. An amine is needed which is reasonably rigid but also contains a few alkyl groups to increase th e cryptates solubility in organic solvents. Tris amine 3-19, synthesized by the Scott group, seemed like an ideal candidate (Figure 3-23). The compound contains three aniline subunits anchored to one another by a central methine carbon as well as six methyl groups, which will help increa se the solubility of the resulting complex. Following the general approach for produc ing salens, a solution containing three equivalents of dialdehyde 3-14 in refluxing absolute ethanol was tr eated with two equivalents of tris-amine 3-19 (Figure 3-24). The reaction cond itions produced a bright orange solid that was analyzed via 1H NMR spectroscopy. Because the cryptate is highly symmetric, the spectra of the

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85 solid showed only eight proton signals. C onsequently, under the reaction conditions the formation of cryptate 3-20 (yield 73%) wa s favored over the formation of a polymer. Single crystals of 3-20 were obtained from a THF-MeOH/CH3CN diffusion (Figure 3-25). The structural data shows that the 3-20 complex is a pseudo-C3 symmetric complex and that the angle of the aniline subunits a llows the formation of 3-20 without significant di stortion to the urea subunit, approximately 6.0 as was seen in complex 3-15a-Zn(II) py. The distances between the nitrogens (average N N 6.98 ) and oxygens (average O O 7.22 ) that would be used to chelate metal ions are large, maki ng this complex ill suited for metal chelation, but this allows for the use of six O-H and six N-H donor s, which all point to the inside of the cavity, for binding purposes. There is no indication of intramolecular hydrogen bonding between the atoms of the complex. The size of the cavity pr oduced, 10.40 seems too large to produce 1:1 complexes with the anions used in the previ ous studies, but the cavit y could be used to encapsulate larger and biologica lly relevant substrates. Molecular recognition of carbohydr ates is crucial in many biol ogical processes and relies upon hydrogen bonding interactions. Urea groups are an appropriate choice because of their dual hydrogen bonding donor-acceptor nature, which can be exploited to accommodate the six polar groups on the monosaccharide, the four hydroxyl and the two ether groups. When testing recognition ability, monosaccharides and short ol igosaccharides are used as substitutes for carbohydrates.85 1O -octyl-D-glucopyranoside ( Glc) and 1O -octyl-D-glucopyranoside ( Glc) (Figure 3-26) are the most frequently used monosaccharides for testing new receptors because the monosaccharides are commercially av ailable and highly soluble in most organic solvents.86 The binding event is typically studied and measured by 1H NMR spectroscopy.

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86 Compound 3-20 was tested for its ability of bind monosaccharides. Due to the decreased flexibility of 3-20, the crypatate could prefer one configuration of th e monosaccharide to the other. For these experiments, the receptor or the monosaccharide can be the titrating agent. Complex 3-20 was tested both ways with Glc and Glc. For all four experiments, the 1H NMR signals of the receptor and the 1H NMR signals of the monosacch aride were monitored. During the titration experiments, there were no discer nable changes in the signals for either. The solution containing both were monitored over multiple days to determine if binding would take place over a longer period of time, but no changes were present in the 1H NMR spectra of the samples. Because Glc and Glc are the benchmark for monosaccharide binding no other monosaccharides were tested. Conclusions Urea aldehyde 3-10 was used to produce a m ixed metal salen complex containing two triphenoxymethanes and one urea subunit, whil e dialdehyde 3-14 was used to produce ureabased macrocycles with diamines and a large urea-based cryptate with tris -aniline 3-19. The urea-based macrocycles can be metallated with Zn(II) ions, which forms complexes containing two ligands and four Zn atoms. The complexes can be treated with Lewis bases under specific conditions to produce discrete metallated macrocyc les or infinite solids. All of the urea-based and mixed N-H/O-H complexes were tested for substrate binding, and the data suggests that the complexes were not suitable for the binding of any of the tested substrates. Experimental 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 analys es and Mass spectrometry were performed at the

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87 in-house facilities in the De partment of Chemistry at the University of Florida. All solvents were ACS or HPLC grade and used as purchased. Synthesis of 3-13-La(III) A slurry of 2-4b*-La(III) (0.35g, 0.34mmol) in boiling ab solute ethanol was treated with a few drops of triethylamine. This mixtur e was immediately treate d with 0.12 g of 3-10 (0.37mmol). Upon the addition of this reagent, both solids dissolved and a green solution was produced. After a few minutes of stirring a yellow precipitate formed. The product was isolated via filtration and drie d to obtain 0.30 g of product. Yield of 68%. Crystals suitable for X-ray diffraction were grown by a toluene/pentane diffusion. 1H NMR [CD2Cl2] = 8.51 (s, 1H), 8.08 (bs, 1H), 8.02 (s, 1H), 7.07 (s 2H), 7.00 (m, 2H), 6.96 (bs, 1H), 6.94 (s, 1H), 6.83 (m, 3H), 6.80(s, 1H), 6.72 (m, 2H), 6.66 (bs, 1H), 6.53 (s, 1H ), 6.50 (s, 2H), 4.01(t, 1H), 3.69 (bs, 1H ), 3.46 (d, 1H), 3.18 (bt, 1H), 3.01 (t, 1H), 2.84 (d, 1H), 2.19 (s, 3H ), 2.14 (s, 3H ), 1.90 (bs, 3H), 1.73 (bs, 2H), 1.29 (s, 9H). 13C NMR [CD2Cl2] = 169.13, 152.92, 150.06, 149.86, 140.06, 137.20, 131.46, 129.88, 129.79, 129.19, 128.49, 123.74, 123.35, 121.86. ESI-FT-ICR-MS: calcd for C74H80N6O9LaNa 1343.5070; found 1343.4966 [M+Na]+. General Procedure for the Synthesis of Compounds 3-15 A portion of 3-14 was added to 250 mL of abso lute ethanol and the resulting solution was brought to a reflux. The refluxing ethanol m ixture immediately changed color upon the addition of the preferred diamine, which was allowed to reflux for 24 hours. Th e desired pure product precipitated from the solution and was co llected via filtration and dried. Compound 3-15a Using 1.00 g (2.42 mmol) of 3-14 and 0.18 g (2.42 mm ol) of 1,2-Phenylenediamine afforded 1.24 g (77%) of product. 1H NMR [DMSO-d6] = 13.58 (s, 4H), 8.93 (s, 4H), 8.85 (s, 4H), 8.28 (s, 4H), 7.49-7.46 (m, 8H), 7.36 (s, 4H), 1.29 (s, 9H). 13C NMR [DMSO-d6] =

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88 153.07, 149.44, 142.09, 140.80, 127.37, 122.71, 119.81, 117.61, 33.99, 31.23. ESI-FT-ICR-MS: calcd for C58H64N8O6H 969.5022; found 969.4977 [M+H]+. Compound 3-15b Using 1.00 g (2.42 mmol) of 3-14 and 0.33 g (2.42 mm ol) of 4,5-dimethyl-1,2Phenylenediamine afforded 1.86 g (75%) of product. 1H NMR [DMSO-d6] = 13.68 (s, 4H), 8.92 (s, 4H), 8.83 (s, 4H), 8.24 (s, 4H), 7.34 (s, 4H), 2.32 (s, 12H), 1.29 (s, 36H). 13C NMR [DMSO-d6] = 178.85, 167.62, 164.06, 155.17, 153.99, 150.92, 141.83, 134.92, 132.14, 69.40, 48.45, 45.72. 33.60. ESI-FT-ICR-MS: calcd for C62H72N8O6H 1025.5648; found 1025.5727 [M+H]+. Compound 3-15c Using 0.50 g (1.21 mmol) of 3-14 and 0.07 g (1.21 mm ol) of Ethylenediamine afforded 0.42 g (40%) of product. 1H NMR [DMSO-d6] = 13.91 (s, 4H), 9.02 (s, 4H), 8.65 (s, 4H), 8.28 (s, 4H), 7.03(s, 4H), 3.88 (s, 18H), 1.27 (s, 36H). 13C NMR [DMSO-d6/CDCl3] =167.10, 152.99, 150.28, 139.61, 127.90, 120.26, 119.96, 115.95, 59.56, 48.64, 33.74, 31.10. ESI-TOFMS: calcd for C50H64N8O6H 873.5022; found 873.5018 [M+H]+. General Procedure for the Synthesis of Compounds (3-15-Zn(II))2 Macrocycles 3-15 were added to 50 mL of THF, treated with a few drops of triethylamine, and the resulting solution was brought to a reflux. A portion of the Zn (II) Acetate was added to the refluxing mixture, which was allowed to refl ux for 12 hours. The resulting pure metal dimers were obtained by the removal of the solvent in vacuo. Compound (3-15a-Zn(II))2 Using 0.15 g (0.15 mmol) of macrocycle 315a and 0.07 g (0.33 mmol) of Zn(II) Acetate afforded 0.24 g (73%) of product. Crystals su itable for X-ray diffr action were grown by a diffusion of THF/Pentane. 1H NMR [CDCl3] = 9.09 (s, 2H), 8.82 (s, 4H), 8.81 (s, 2H), 8.71 (s,

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89 2H), 8.51 (s, 4H), 8.24 (s, 2H), 7.98 (s, 2H), 7.96 (s, 2H), 7.80 (d, 2H, 2.4 Hz), 7.71 (d, 2H, 2.4 Hz), 7.67 (d, 2H, 2.4 Hz), 7.62 (s, 2H), 7.60 (s, 2H), 7.36-7.26 (m, 6H), 7.12 (t, 2H, 3.0 Hz), 7.04 (s, 2H), 6.66 (d, J = 2.4 Hz, 2H), 6.58 (d, J = 2.4 Hz, 2H), 6.55 (d, J = 2.4 Hz, 2H), 6.24 (d, J = 2.4 Hz, 2H), 2.07 (s, 9H), 1.47 (s, 9H), 1.20 (s, 18H), 1.17 (s, 18H), 1.13 (s, 18H). 13C NMR [CDCl3] = 178.67, 166.72, 165.25, 163.30, 161.61, 159.99, 158.99, 158.45, 158.41, 154.66, 153.91, 142.00, 140.82, 140.31, 139.30, 138.64, 136.86, 135.93, 134.75, 133.54, 131.74, 130.44, 129.66, 128.76, 127.71, 127.37, 126.91, 126.21, 124.92, 124.67, 122.30, 121.58, 119.64, 118.99, 118.17, 116.93, 116.20, 115.99, 115.47, 115.13, 108.10, 98.62, 67.82, 67.57, 58.68, 45.23, 34.32, 34.12, 34.11, 33.79, 33.45, 32.20, 31.79, 31.55, 31.45, 29.38, 27.99, 24.13, 23.60, 23.31, 9.08, 8.44. ESI-TOF-MS: calcd for C116H120N16O12Zn4H 2191.6484; found 2191.6502 [M+H]+. Compound (3-15b-Zn(II))2 Using 0.15 g (0.15 mmol) of macrocycle 315b and 0.07 g (0.33 mmol) of Zn (II) Acetate afforded 0.27 g (80%) of product. 1H NMR [CD2Cl2] = 9.07 (s, 1H), 8.82 (s, 2H), 8.65 (s, 1H), 8.52 (d, J = 3.0 Hz, 2H), 8.23 (s, 2H), 7.98 (s, 1H), 7.93 (s, 2H), 7.75 (d, J = 3.0Hz, 2H), 7.67 (t, J = 2.4 Hz, 2H ), 7.41 (s, 2H), 7.38 (s, 2H), 7.05 (s, 2H), 6.86 (s, 2H), 6.74 (s, 2H), 6.65 (s, 2H), 6.61(d, J = 3.0 Hz, 2H ), 6.23 (d, J = 3.0 Hz, 2H ), 2.69 (bs, 8H), 2.44 (s, 12H), 2.30 (s, 12H), 1.49 (s, 18H), 1.22 (s, 18H), 1.18 (s, 18H), 1.12 (s, 18H). 13C NMR [CD2Cl2/DMSO-d6] = 160.18, 154.28, 137.53, 136.24, 135.30, 132.40, 123.45, 121.38, 116.76, 116.62, 34.04, 31.48, 19.86. (Upon the addition of DMSO-d6 the complex disassociates.) ESI-TOF-MS: calcd for C124H136N16O12Zn4H 2303.7740; found 2303.7817 [M+H]+. Compound (3-15c-Zn(II))2 Using 0.15 g (0.17 mmol) of macrocycle 315c and 0.08 g (0.36 mmol) of Zn(II) Acetate afforded 0.24 g (71%) of product. 1H NMR [CDCl3] = 8.95 (s, 2H), 8.67 (s, 2H), 8.63 (s, 2H), 8.36 (s, 2H), 8.08 (s, 2H), 8.05 (s, 2H), 8.02 (s, 2H ), 7.93 (s, 2H), 7.85 (s, 2H), 7.71 (s, 2H), 7.59

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90 (s, 2H), 6.82 (s, 2H), 6.47 (s, 2H), 6.33 (s, 2H), 6.07 (s, 2H), 5.93 (bs, 8H), 2.00 (s, 16H), 1.34 (s, 18H), 1.31 (s, 18H), 1.23 (s, 18H), 1.21 (s, 9H), 1.09 (s, 9H). 13C NMR [CDCl3] = 177.69, 170.66, 170.07, 169.58, 168.05, 158.31, 158.18, 157.99, 157.62, 154.81, 153.97, 140.74, 135.76, 134.92, 133.66, 133.15, 131.98, 129.94, 129.78, 126.74, 125.31, 124.01, 123.71, 121.41, 119.47, 118.35, 116.54, 114.76, 58.44, 56.70, 54.85, 54.40, 34.35, 34.15, 33.93, 33.84, 31.94, 31.80, 31.66, 31.57, 22.92, 8.70, 8.34. ESI-TOF-MS: calcd for C100H120N16O12Zn4H 1999.6476; found 1999.6547 [M+H]+. Synthesis of 3-15a-Zn(II) py A portion of com pound (3-15a-Zn(II))2 was partially dissolved in THF. Pyridine was added drop-wise to this solution until the remain ing solid dissolved in the THF solution. Pentane was allowed to slowly diffuse into the THF-pyridine solution, which produced single crystals of the desired product. 1H NMR [CDCl3-DMSO-d6] = 8.87 (s, 4H), 8.86 (s, 4H), 8.85 (s, 4H), 8.54 (d, 4H), 8.45 (s, 4H), 7.44-7.38 (m, 4H), 7.367.34 (m, 4H), 6.98 (s, 4H), 1.36 (s, 9H). 13C NMR [CDCl3-DMSO-d6] = 159.05, 159.01, 152.77, 147.97, 138.39, 135.20, 133.68, 130.70, 125.76, 122.65, 122.13, 114.97, 66.09, 32.58, 32.02, 30.15, 24.07, 22.20. Synthesis of 3-20 A portion of 0.75g (1.82 mmol) 3-14 was added to 250 m L of absolute ethanol. The resulting solution was brought to a reflux. 0.54 g (1.21 mmol) of the 3-19 was added to the refluxing ethanol mixture, which immediately turn ed orange. The solution was allowed to reflux for 24 hours. The pure product was collected by filtration and dried to give 0.92g pure orange solid in a yield of 73%. Crystals suitable fo r X-ray diffraction were grown by a diffusion of THF-MeOH/Acetonitrile. 1H NMR [CD2Cl2] = 8.50 (s, 6H), 8.27 (s, 6H), 7.05 (s, 12H), 6.71 (s, 6H), 6.43 (s, 2H), 3.68 (s, 18H), 2.34 (s, 9H), 1.31(s, 54H). 13C NMR [THF-d8] = 165.87, 156.72, 153.83, 149.18, 146.35, 142.19, 139.20, 133.39, 129.52, 124.60, 122.10, 121.88, 120.11,

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91 118.50, 60.41, 35.13, 32.01, 30.80, 16.88. ESI-TOF-MS: calcd for C123H144N12O27Na 1995.0019; found 1995.0006 [M+Na]+. Figure 3-1. Depiction of the interacti on between a urea-containing receptor and N, N -dimethylp-nitroaniline. Figure 3-2. Illustration of m -phenyl spaced bis-urea (3-1) and o-phenylenediamine-based (3-2) receptors. Figure 3-3. Depiction of two urea re ceptors with tris-amine spacers.

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92 Figure 3-4. Illustration of two cy clic urea-based anion receptors. Figure 3-5. Illustration of a urea based receptor that is templated by a Pt(II) metal center. Figure 3-6. Illustration of urea-based colorimetric sensors for anion binding.

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93 Figure 3-7. Depiction of tripodal urea receptors containing Lu(III) and Co(III) ions. Figure 3-8. Illustration of the synthetic scheme used to produce urea salen 3-11.

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94 Figure 3-9. Schematic drawing of a bifunctional anion receptor. The coordination of the chloride with two O-H and two N-H donors is similar to the binding of chloride in the ClC chloride channels found in E. coli La N O N HO O OH N N HO HO OH H N O O H N + La N O N O N HO HO NH O NH 2 i 3-10 3-13-La(III) 2-4b*-La(III) Figure 3-10. Schematic drawing of the synthesi s of the mixed metal sa len 3-13-La(III). (i) ethanol, triethylamine, and heat.

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95 Figure 3-11. Depiction of the solid-state st ructure of 3-13-La(III). The hydrogen atoms are omitted for clarity.

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96 Figure 3-12. Synthetic scheme for urea dialdehyde 3-14. Figure 3-13. Depiction of the synthesi s of urea-based macrocycles 3-15a/b/c.

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97 Figure 3-14. Schematic drawing of the supramolecular box (3-16)2. Figure 3-15. Depiction of the 1H NMR spectrum of 3-15b-Zn(II) in CD2Cl2.

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98 O O N N O O O N H O N N N H Zn1Zn2Zn4Zn3O O O O O O O O N N O O N N N O O N N N NH O NH OH OH N N HN O HN HO HO N N = = 3-15a3-15b3-15c = (3-15a-Zn(II))2(3-15b-Zn(II))2(3-15c-Zn(II))2i Figure 3-16. Illustration of the synthetic route used to produced (3-15a/b/c-Zn(II))2. (i) Zn(II) Acetate, refluxing THF, trie thylamine, 12 hours. The c oordinated THF molecules on Zn1 and Zn2 were omitted for clarity.

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99 Figure 3-17. Solid-state st ructure of (3-15a-Zn(II))2 (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity.

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100 Figure 3-18. Solid-state structure of 3-15a-Zn(II) py (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity.

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101 Figure 3-19. Schematic representa tion of the interactions in th e solid produced when (3-15aZn(II))2 is treated with 1,2bis(4-pyridyl)ethylene.

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102 Figure 3-20. Schematic representation of the inte ractions in the solid produced when (3-15aZn(II))2 is treated with 4-4-bipyridine.

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103 Figure 3-21. Schematic drawing of the metal template synthesis of dinuclear lanthanide(III) and yttrium(III) cryptates. (i) trieth ylamine, methanol, 30 minutes. Figure 3-22. Illustration of the tris -amines Tame (left) and Tach (right). Figure. 3-23. Depiction of the tris -amine 3-19.

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104 Figure 3-24. Illustration of th e synthetic route to produce cryp tate 3-20. (i) ethanol, reflux, 24 hours.

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105 Figure 3-25. The solid-state structure of cryptate 3-20 (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity. Figure 3-26. Illustration of 1O -octyl-D-glucopyranoside (left) and 1O -octyl-Dglucopyranoside (right).

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106 Table 3-1. Crystallographic data for compounds 3-13-La(III), (3-15a-Zn(II))2, 3-15a-Zn(II)py, and 3-20. 3-13-La(III) 0.5C7H8 (3-15a-Zn(II))2 0.5C5H12-2H2O 3-15a-Zn(II) py2THF 3-20 THF4MeOH Formula Crystal System Space Group Z a () b () c () ( ) ( ) ( ) Vc (3) Uniq. data coll./obs. R1[ I 2 (I)data] wR2[ I 2 (I)data] C77.5H86N6O10La Triclinic P-1 2 13.0744(14) 13.08037(15) 21.400(2) 96.583(2) 96.091(2) 93.798(2) 3802.9(7) 16536/11089 0.0448 0.1180 C126.5H146N16O16Zn4 Monoclinic P2(1)/n 4 15.6881(9) 23.9208(14) 35.079(2) 90.00 91.5050(10) 90.00 13159.6(13) 30678/19181 0.0582 0.0862 C76H78N10O8Zn2 Monoclinic C2/c 4 25.858(14) 17.056(9) 20.237(10) 90.00 104.364(16) 90.00 8646(8) 5892/2611 0.0502 0.1508 C131H167N12O32 Monoclinic P2(1)/n 35 19.692(3) 21.338(3) 36.434(5) 90.00 98.896(2) 90.00 15125(3) 20989/7159 0.0941 0.1578

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107 CHAPTER 4 CHIRAL METAL SALENS INCORPORATING TRIPHENOXYMETHANES FOR CATALYSI S Introduction Metal Schiff base com plexes are widely used in a large variety of catalytic processes. The use of Schiff base ligands to produce novel cataly sts continues to grow in popularity because of the many advantages afforded by the basic properties of the ligand. Salen-type ligands, which are produced by a simple condensation reacti on between a primary amine and the aldehyde functionality of a salicylaldehyde, are easy to synthe size. The ability to readily isolate the ligand as well as the commercial availability of chiral primary amines and chiral salicylaldehydes make Schiff base ligands ideal for producing libraries of chiral ligands used to make chiral metal complexes. A large library of chiral metal complexes is advantageous when screening for catalytic activity because the smallest solubil ity or structural change could produce an ideal catalyst. Bis-Schiff base ligands are tetr a-dentate and use the lone pair s of the two nitrogen imines and the oxygen from the phenols to stabilize a wide variety of metal ions with varying oxidation states.53 Metal salen catalysts are produced when a wide assortment of metals (Mn, Cr, Co, V, Cu, Ti, Ru, Rh, Au, Zn, and Al), which are chelat ed in a distorted square planar or square pyramidal geometry.87-90 The ligands help control the performance of the metals in a large variety of useful catalytic transforma tions such as: alkene epoxidation (Mn)91-93 and aziridination (Cu),94, 95 epoxide ring opening and Hetero-Diels-Alder (Cr),96, 97 epoxide kinetic resolution 98-101 and CO2 insertion (Co), sulfimidation102, 103 and cyclopropanation 104, 105(Ru), alkene 106, 107 and alkyne 108addition to aldehydes and ketone s (Zn), as well as others. In order to control catalytic activity, Lewis acid catalysts must have specific properties. First, the metal system must be well defined and not produced in situ which is especially

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108 important for catalysts that cont ain a first row transition metal. Metal complexes containing a first row transition metal tend to make octahedral complexes, and a saturated metal center would be detrimental to the catalytic process. Ho wever, some transitional metal complexes not produced in situ can still favor octahedral metal centers, but saturated metal centers can be prevented by designing bulky ligands which block the ancillary coordination sites. Catalytic activity is also affected by the size and oxidation state of the metal and the nature of the substituents around the metal center. Therefore, metal salens seem ideal Lewis acid catalysts because they can stabiliz e a variety of metal ions with a assortment of oxidation states and the aldehyde used to make the salen can be easily modified to produce the ideal environment for the metal center. Metal sa len catalysts are also advantageous because they can be nucleophiles as well as electrophiles,53 which allows chiral information to be transferred by the activation of the nucleophile or vi a the coordination of the electroph ile to the Lewis acid center. But, to control the diastereofacial preference, th e trajectory and the orient ation of the substrate must be controlled.53 Introducing bulky groups on the aroma tic aldehyde, which influences the substrate but does not block it from the metal center, can influence these factors. The most readily recognized metal salen catalyst is Jacobsens catalyst, which was developed in 1991.109 The salen ligand of this catalyst contains an R, R -cyclohexyl diimine bridge and t -butyl substituents on the ortho and para positions of the phe nolate (Figure 4-1). The ligand was metallated to produc e a Mn(III) complex with an ax ial Cl ligand. The catalyst was used in reactions containing cis -olefins and NaOCl and was found to produce asymmetric epoxides with enantomeric excesse s (ee) of greater than 90%. Kochi and co-workers110 studied the mechanism of the transformation of olefins to epoxides by Mn(III) salens. They found that an Mn (V)=O species was a key intermediate

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109 produced when the Mn(III) salen reacted with the NaOCl, which later reacted with the olefin to give the desired epoxide. The selectivity of the reaction with catalyst 4-1 was attributed to a side-on interaction between the olefin and the oxygen on the metal center, with the olefin approaching the metal from over the diimine bridge. The t -butyl groups on the phenolate subunits block the other three possible side-on approaches. The Addition of Et2Zn to Aldehydes by Chiral Metal Salen Complexes Since the first reports by Oguni111 and Noyori,112 the asymmetric alkylation of aldehydes by diethylzinc has been used as a benchmark for potential chiral ligands. This reaction has been extensively studied in the pr esence of catalytic amounts of -amino alcohols for the synthesis of optically active secondary alcohols.113 However, the use of chiral salen ligands to promote this transformation was not reported until 1996 by Cozzi and coworkers.114 The same chiral ligand used for Jacobsens catalyst was used to generate a Zn(II) salen in situ by the addition of one equivalent of Et2Zn (Figure 4-2). The generated complex was then used to promote the organic transformation. The desired secondary alcohol wa s produced in high yields with the highest ee value (70%, S) in toluene at a starting temperature of -40 C then warming to room temperature over a 24 hour period. Other chiral Schiff base sale ns have been used to perfor m the asymmetric alkylation of aldehydes. Keller and coworkers115 synthesized an axially chiral salen, 4-2, by using (P) or (M)6,6-dimethyl[1,1-biphenyl]-2,2-dimethanamine and a variety of aldehydes (Figure 4-3). Catalyst 4-2-Zn(II) was made in situ and then used in the reaction scheme shown in Figure 4-2. The best asymmetric induction (25 % ee) and the highest yield (83 %) were reached when the ligand with R1=MeO and R2=H was used in toluene. Because of the disappointing results from the reactions with 4-2-Zn(II), the transiti on metal bound by the O,N,N,O binding core of the

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110 salen ligand was changed, which led to the optim ization of the asymmetr ic induction. Al(III), Ti(IV), Mn(II), Fe(II), Co(II), Ni(II), and Cu(II) complexes were formed from the ligand with R1=MeO and R2=H to determine which metal would provide good reactivity and enantioselectivity. Catalyst 42-Co(II) gave the best values (95 % yield and 79% ee) and the enantioselectivity could be further enhan ced (90% ee) by using the ligand with R1=EtO. The Cycloaddition of Carbon Dioxide to Epoxides w ith Metal Salen Catalysts During the past two decades the transforma tion of carbon dioxide into useful organic compounds has attracted much inte rest due to the economic as we ll as environmental benefits.116119 One class of useful organic comp ounds produced through the fixation of CO2 is cyclic carbonates, which are used as or ganic synthetic intermediates, monomers, aprotic solvents, pharmaceutical or fine chemical intermedia tes, and in biomedical applications.120 Enantiomerically pure cyclic carbonates have be en produced using two methods: the insertion of CO2 into enantiomerically pure epox ides or through a coupling r eaction of carbon dioxide with the racemic epoxide catalyzed by chiral Co(III)salen catalysts.100, 101, 121-124 Chiral Co(III) salen catalysts are thought to produce enantiomerically pu re carbonates by selectively binding one enantiomer of the chosen racemic epoxide. The coordinated epoxide will then be attacked by a nucleophile or activated CO2 on the less substituted carbon regioselectively. This will lead to enantioselec tive ring opening of the epoxide, which will then continue on to form chiral cyclic carbona tes via intermolecular cyclic elimination.121 The possible pathways for the direct synthesis of optically active carbonates from racemic epoxides are shown in Figure 4-4. The conversions typically take place in a stai nless steel vessel charged with the desired epoxide, catalyst, and co-cat alyst, pressurized with CO2, and stirred at the chosen temperature for the appropriate amount of time. Catalyst 4-3 has been the preferred catalyst used, with varying

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111 axial ligands (X), to produce enantiopure propylene carbonate from racemic propylene oxide (Figure 4-5) and CO2. As seen in Table 4-1, various form s of catalyst 4-3 can produce chiral propylene carbonate at moderate to high ees (49-84%) and modera te yields when the reaction temperatures ranged between -5 C and 25 C. Wide ranges of co-cat alysts were tested, which enhanced the activity of the reaction and the enanti opurity of the carbonate. The most recent example of chiral Co(III) sale ns used in this transformation were made from ligands containing multiple chiral elements known as BINAD (BINAD=Bis(1,1-2hydroxy-2-alkoxy-3-naphthylidene)-1,2-cy clohexane-diamine) (Figure 4-6).124 For catalyst 4-4, four conformers were produced, ( R,R,R,R ), ( S,R,R,S ), ( R,S,S,R ), and ( S,S,S,S), while only two conformers of 4-5 were synthesized, ( R,R,R,R,R ) and (S,R,R,S,R,R ). Reactions containing propylene oxide, 0.0005 mol% 4-4 or 4-5, and the co-catalyst PTAT run at 25C in 5 atm of CO2 had higher enantioselectivity when the ( R,R,R,R ), ( S,S,S,S), and ( R,R,R,R,R ) catalysts were used. Overall, the best enantioselectivity (95 %) with regard to th e synthesis of chiral propylene carbonate was accomplished with catalyst 4-4b (( S,S,S,S), R=OBu, X=OAc) with PTAT at -20C over a 100 hour period. Unfortunately, the yield for this conversion was only 4.9%. General Approach for Producing New Chiral Metal Salen Complexes for Catalysis Lewis Acid catalysts have been studied extensively; however, there is a continued need for catalysts that are more efficient and se lective. Also, Lewis Acid catalysts can promote a large variety of organic transformations, and if the catalyst possesses the proper ligand and metal environment then the transformations can be regi oor stereo-selective. Because the ligand and metal environments are crucial for selective catalysis it is important to be able to produce large chiral ligand libraries that can chel ate a large variety of metal ions.

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112 Scott group member, Dr. Eric Libra, has produced extremel y bulky chiral metal salens complexes incorporating triphenoxymethanes. Chiral Ni(II) triphenoxymethane salen (Figure 47) was produced with R,R -1,2-diaminocyclohexane.43 and the solid-state structure of this complex showed that the geometry provided by the chiral amine did not tr anslate through the rest of the salen ligand. Specifically, in the two comp lexes that crystallized in the asymmetric unit each had phenols in different orientations. Even though the bulkiness of the complex should enhance the selectivity of the possible catalytic products, the rotational freedom of the bulky substituents make the complex unsuitable for sel ective catalysis. Thus, a different chiral amine should be used to produce the bulky salen liga nd and the rotational freedom of the phenol substituents must be reduced. ( R )-2,2-diamino-1,1-binapthylene or BINAM was chosen to produce the new salens because the size and conformation of the napthyl substituents would add bulk to the top of the catalyst as well as translate its geometry to th e rest of the salen molecule. A condensation reaction with BINAM and aldehydes 4-6a-d gave th e chiral salen ligands 4-7a-d (Figure 4-8). The solubilities of the BINAM salens varied signi ficantly. Chiral 4-7a wa s soluble in all polar and non-polar solvents tested, which is an undesirable characteristic of the ligand when producing the metallated complex that are typica lly isolated only if they precipitate upon formation. Nonetheless, the racemic derivative of 4-7a was soluble in only a few solvents, so this ligand was used to determine if structur ally the metal salen system would be a good candidate for asymmetric catalysis. Racemic 4-7a-Zn(II) and racemic 4-7a-Co(II) were isolated when racemic salen 4-7a was treated with the appropriate metal salts. Th e solid-state structure of 4-7a-Zn(II) in a noncoordinating solvent showed a four-coordinate, di storted tetrahedral Zn center and a metal salen

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113 complex with its overall geometry dictated by th e BINAM subunit. As seen previously in the solid-state structure of the Ni (II) salen complex in Figure 4-7, the peripheral phenols of 4-7aZn(II) still possessed a large degree of rotational freedom. In order to produce a bulky Lewis Acid catalyst best suited to control the trajecto ry of the approaching s ubstrate, 4-7a-Zn(II) was treated with one equivalent of Ti(IV)isopropoxide (Figure 4-9). The Ti(IV) ion was coordinated by the four peripheral phenols, which rigidified the system as well as created a channel that could be used to control the substrates approach to the Zn(II) metal center. Also, one side of the metal center is blocked by the position of one phenol, thus further reducing the possible modes of substrate attack. 4-7a-Co(II )/Ti(IV) complex is isostructural to that of the corresponding Zn(II) derivative with a five-coordinate, trigonal pyramidal metal(II) center with similar metalligand bond lengths as those in sim ilar Co(II) and Zn(II) BINAM complexes.125, 126 The solid-state structures of 4-7a-Zn(II)/Ti (IV) and 4-7a-Co(II)/Ti(IV ) suggest that these complexes could be suitable catalysts for en antioselective organic transformations, but the solubility of chiral salen 4-7a did not allow for the formation of clean metal complexes. As a result, chiral salen 4-7b was synthesized to addre ss the solubility issues of 4-7a by replacing the t -butyl substituents with methyl groups. The so lubility of salen 4-7b di d decrease but not enough to allow for the isolation of clean metal comple xes. Consequently, BINAM salen ligands 4-7c and 4-7d containing NO2 or Br moieties were synthesized. Th e solubilities of chiral 4-7c and 47d were comparable to the solubility of racemic 4-7a and the desired Zn(II) as well as Co(II) derivatives were readily produced.

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114 Results and Discussion The resea rch presented within this chapter consists of completing the synthesis of the chiral and racemic dinuclear cat alysts produced from the BINAM ligands 4-7c and 4-7d as well as the data from the catalytic stud ies performed with the catalysts. Synthesis of Chiral and Racem ic D inuclear BINAM Catalysts The metallation of 4-7c/d-Co(II) and 4-7c-Zn(II) (attempts to produce chiral 4-7d-Zn(II) were unsuccessful) was accomplished by treating a dich loromethane solution containing the metal salen with a portion of Ti(IV ) isopropoxide and stirring for 12 hours (Figure 4-10). A solid was isolated upon the removal of the solvent, which was analyzed via 1H NMR spectroscopy. For 4-7c-Zn(II)/Ti(IV), the 1H NMR spectrum showed that the reaction produced a single clean product. The addition of the Ti(IV ) ion, which is meant to lock the conformation of the catalyst, produced pronounced changes in the 1H NMR spectrum when compared to 4-7cZn(II). Many of the signals in the aromatic region shifted or disappeared, which was accompanied by the shifting of all four alkyl sign als. Paramagnetic complexes such as 4-7cCo(II) and 4-7d-Co(II) are not usually characterized by 1H NMR spectroscopy, but both complexes produced readable 1H NMR spectra, which allowed for the chelation of the Ti(IV) ion to be monitored by 1H NMR spectroscopy. For example, the 1H NMR spectrum of 4-7d-Co(II) shows 24 signals ranging from 60.20 ppm to 51.76 ppm and upon the addition of the Ti (IV) ion the spectrum shows 21 signals rang ing from 26.28 ppm to -9.45 ppm. Dinuclear complexes 4-7c-Co(II)/Ti(IV) a nd 4-7c-Zn(II)/Ti(IV) both produced single crystals suitable of X-ray diffraction from a slow diffusion of pentane into THF. The solid-state structure of 4-7c-Co(II)/Ti(IV) (F igure 4-11) is similar in structure to the 4-7a-Co(II)/Ti(IV), which has analogous Co-N and Co-O distance wh en compare to previously reported Co(II) BINAM salens.126 The bond lengths and angles produced between the titanium center and the

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115 phenols were also typical.127 The racemic derivatives of the dinuclear complexes were also prepared, which would be initially used to test if the complex was capable of performing the chosen organic transformations. The racemic BINAM ligands were prepared in the same manner as the chiral BINAM ligands (4-7c and 4-7d, Figure 4-8). The Co(II) and Zn(II) metal complexes, including 4-7d-Zn(II), were synthe sized and isolated under a variety of reaction conditions, which allowed for the formation of all four racemic dinuclear complexes under the reaction conditions used to produce the chiral dinu clear complexes. As would be expected, the 1H and 13C NMR spectra of the racemic complexes were identical to the spectra of the corresponding chiral complexes. The Addition of Et2Zn to Benzaldehyde with 4-7c/d-M(II) and 4-7c/d-M(II)/Ti(IV) The asymmetric alkylation of aldehydes by diethyl zinc has been used as a benchmark for potential chiral catalysts and the transformation can be facilitated by a wide variety of metal centers, which is why this transformation was chosen to test the m ononuclear and dinuclear BINAM salen complexes. First, the reaction conditions were optimized using the racemic complexes 4-7c/d-Co(II), 4-7c/d-Co(II)/Ti(IV), 4-7c-Zn(II), and 4-7c-Zn(II)/Ti(IV). Racemic 4-7d-Zn(II) and 4-7dZn(II)/Ti(IV) were not tested sin ce the corresponding chiral derivative could not be produced. Initially, a reaction mixture containing 10.0 mo l% catalyst and two equivalents of ZnEt2 in toluene was allowed to stir at room temperat ure for 24 hours. The catalyst was removed from the reaction mixture, which was then analyzed by 1H NMR spectroscopy. The spectrum of the crude mixture showed that approximately 20 % of the benzaldehyde was converted to the secondary alcohol. Under the same reaction cond itions, it was discovered th at the quantitative conversion of the benzaldehyde took 96 hours. As a result, these c onditions were used to test if the corresponding chiral complexes could produce the asymmetric secondary alcohol.

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116 As seen in Table 4-2, both the mononuclear and dinuclear catalysts 4-7c/d can produce chiral 1-phenylpropan-1-ol at room temperature. The % ees for the transformations performed by catalysts 4-7c-Co(II) and 4-7c-Zn(II)/Ti(IV) were insignif icant and produced a racemic mixture of the alcohol, while the best enantiose lectivity was seen with catalysts 4-7d-Co(II) and 4-7d-Co(II)/Ti(IV). The dinuclear cata lysts preferentially produced the S conformer of the alcohol, but the mononuclear catalysts produced both the R and the S conformers of 1phenylpropan-1-ol. Also, the data suggests, for this reaction under the given conditions, that the locking of the bulky phenol substituents does not always produce enhanced enantiopurity of the product. It was hoped that the reactivity of comple xes 4-7c/d-Co(II) and 4-7c/d-Co(II)/Ti(IV) could be enhanced by oxidizing the Co(II) metal ce nter to produce the Co(III) derivative. Many methods and reagents (H2O2, I2/AgSBF6, NOSbF6, and various acids) were employed to produce the desired metal complex. The addition of each reagent turned the orange solution containing the Co(II) complex to dark brown, which usually indicates a successful oxidation of the metal center. Unfortunately, the brown re action mixtures gave paramagnetic 1H NMR spectra and single crystals could no t be grown in order to verify if the desired complex was actually produced. Therefore, these products were not used to perform the selected organic transformations. The Cycloaddition of Carbon Dioxide to Epoxides w ith Mononuclear and Dinuclear BINAM Catalysts Because the BINAM catalysts proved to pr oduce asymmetric secondary alcohols from benzaldehyde, it was decided to use the BINAM catalysts in an attempt to make other asymmetric organic molecules. The production of asymmetric cyclic carbonates through the cycloaddition of carbon dioxide to racemic epoxides was chosen as the next transformation to be

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117 attempted by the BINAM catalysts. Since, the c obalt salen catalysts are the only metal salens reported to have successfully produce asymmetr ic cyclic carbonates, chiral complexes 4-7dCo(II) and 4-7d-Co(II)/Ti(IV) were used as th e catalysts for this transformation. Initially, a reaction mixture containing 0.1 mol % catalyst, 0.2 mol % triethylamine as the co-catalyst, and racemic propylene carbonate in dichloromethane was stirred at 100 C under 500 psi of CO2 for 48 hours. The crude product mixture was analyzed by 1H NMR spectroscopy, which showed approximately 33% conversion to the cyclic carbonate for catalyst 4-7dCo(II)/Ti(IV) and no conversion took place when 4-7d-Co(II) was present in the reaction mixture. Due to the low conversion with the tr iethylamine co-catalyst, a stronger Lewis base was used, DMAP, which caused the reaction of convert quantitatively with catalyst 4-7dCo(II)/Ti(IV) and 4-7d-Co(II) pres ent in the reaction mixture. Attempts were then made to determine if the rate of conversion could be maintained with less catalyst, under milder conditions, or shorter reaction times. Shortening the reaction time to 24 hours lowered the conversion to 35% and cutting the amount of cat alysts in half also caused a drop in the production of the pr opylene carbonate. In creasing the amount of catalyst to 10.0 mol% along with lowering the temperature was prohibitive to the r eaction with conversion ranging between zero and five percent. A summary of this data is presented in Table 4-3. Using the reaction conditions which produced qu antitative conversion, the transformations were repeated with catalyst 4-7d-Co(II)/Ti(IV) and 4-7d-Co( II) and the crude product was analyzed via gas chromatography to measure th e %ee of the propylene carbonate produced. The products obtained from the reactions that used eith er catalyst were found to be racemic mixtures. To ensure that the catalysts was not racemizing the product, the reactions were set up with both conformers of the enantiopure propylene oxide. The conversion of th e enantiopure propylene

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118 oxides to propylene carbonate were lower than the reaction performed with the racemic propylene oxide, which was most likely due to mois ture in the reagent, but the cyclic carbonates produced were essentially enantiopure. Typically lowering the reaction temperature can enhance enantioselectivity of a reaction, but since 4-7d-Co(II)/Ti(IV) and 4-7d -Co(II) are unable to convert th e reactions at even slightly lower temperatures this was not a viable option. Thus, a bulkier epoxide, styrene oxide, was chosen in hopes of increasing the enantioselectivity of the cy clic carbonate. Catalyst 4-7dCo(II)/Ti(IV) is able to fix CO2 to the styrene oxide, but the conversion is poor and the styrene carbonate produced was racemic, and the reaction did not take place at temperatures below 100C. The summary of this data is provided in Table 4-4. As seen in Table 4-5, two other dinuclear BINAM catalysts, 4-7d-Zn (II)/Ti(IV) and 4-7dTi(IV)/Ti(IV), which was produced by treating sa len 4-7d with two equivalents of Ti(IV) isopropoxide, were used in an attempt to produce asymmetric propylene ca rbonate. Catalyst 47d-Zn(II)/Ti(IV) converted the reaction poorly, wh ile 4-7d-Ti(IV)/Ti(IV) produced quantitative amounts of propylene carbonate. The reacti on mixture from the reaction with 4-7dTi(IV)/Ti(IV) was analyzed and found to be ra cemic. Reaction mixtures produced at lower temperatures with 4-7d-Ti(IV)/Ti(IV) showed no evidence of propylene carbonate production when analyzed via 1H NMR spectroscopy. Attempts to Produce Additional B ulky Metal Salen Catalysts Attempts to produce additional metal salen catalysts were made with the amines (-)( R,R )-11,12-Diamino-9,10-dihydro-9,10ethanoanthracene and meso -1,2Diphenylethylenediamine. These amines were ch osen because they are easily synthesized and resolved or commercially availa ble. Also, the angle between the amine groups should be large

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119 enough to translate its geometry to the rest of the salen ligand. The init ial attempts to produce salen ligands with racemic 11,12-Diami no-9,10-dihydro-9,10-ethanoanthracene were problematic due to the low solubility of the resulting products. Thus, (-)-( R,R )-11,12-Diamino9,10-dihydro-9,10-ethanoanthracene was used in stead to produce the corresponding salen ligands. Following the general approach for producing triphenoxymethane salens, a solution with three equivalents of 4-6a-d /f in refluxing absolute ethanol was treated with one e quivalent of the appropriate amine (Figure 4-12 and Figure 4-13). The resulting bright yellow precipitates were the desired ligands 4-8a-c and 4-9a/b/f. All triphenoxymethane salens were characterized by 1H NMR spectroscopy, and the spectra showed that the Schiff base reacti on converted cleanly giving one major product. The reaction conditions produced pure products in high yields and in multi-gram quantities. For the initial attempt to metallate the salen ligands 4-8 and 4-9, Zn(II) was chosen for its ability to produce a neutral diamagnetic complex, allowing for the quick determination of metal complex formation by 1H NMR spectroscopy. Metallation of the 4-8b was accomplished by treating a boiling methanol solution of the ligand with one equivalent of Zn(II) Acetate (Figure 4-14). Within a few minutes, a light yellow precipitate formed, which was analyzed via 1H NMR spectroscopy. Upon the metallation of 4-8b, si gnificant shifting was seen in the aromatic and alkyl signals as well as th e disappearance of the singlet at 12.94 ppm, which corresponded to the phenols used to chelate the metal atom. Single crystals of 4-8b-Zn (II) were obtained from slow diffusion of methanol into acetonitrile. The solid-state structure showed that the reaction conditions produced a metal complex containing two ligands and two Zn(II) metal ions, (4-8bZn(II))2, which was supported by high resolution mass spectrometry.

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120 Attempts were made to produce the desired complex consisting of one ligand and one metal ion. Initially, solutions containing (4-8b-Zn(II))2 and a variety of coordinating solvents were heated and stirred overnight as the means to facilitate the rearrangement of the complex, but the 1H NMR spectrum of the resulting products look ed identical to that of (4-8b-Zn(II))2. Next, a solution containing (4-8b-Zn(II))2 was treated with pyridi ne, which was heated and stirred. Once again analyzing the product with 1H NMR spectroscopy showed that (4-8b-Zn(II))2 had not been effected by the addi tion of pyridine. Lastly, atte mpts were made to force the production the desired metal complex by dissolvi ng 4-8b in a coordinating solvent that also contained pyridine and then trea ting the solution with Zn (II) Acetate. All reaction mixtures analyzed by 1H NMR spectroscopy showed that under th e given conditions metallation did not take place. In order to force the formation of discrete metal complexes, attempts were made to metallate salen ligands 4-8 with the larger Co (II) and Fe(II) metal ions Upon the addition of Co(II) acetate to 4-8a/b, a solid was produced. The isolated solids were both analyzed by 1H NMR spectroscopy and both products gave readable paramagnetic spectra. A purple solid, formed when 4-8a was treated with Fe (II) Acetate, was also analyzed via 1H NMR spectroscopy, but the resulting spectrum was unreadable. Attempts were made to grow single crystals suitable for X-ray diffraction in order to determine if the re sulting solids were similar in structure to that of complex (4-8b-Zn(II))2, but none of the tested solvent co mbinations produced X-ray quality crystals. Therefore, high-reso lution mass spectrometry was used instead, which showed that all three complexes consisted of complexes containing two ligands and two metal centers. The data suggests that the size of the metal ions in the firs t row of transition metals are too small to force ligand 4-8 to produce the discrete metal complexes needed for catalytic studies.

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121 Attempts to metallate ligand 4-9 with Zn(II) ions were unsuccessful, but treating 4-9f with Co(II) Acetate, which had been boiled in absolute ethanol, produced 4-9f-Co(II). The resulting brown solid gave readable paramagnetic 1H NMR spectra as well as single crystals suitable for X-ray diffraction. The solid-state structure of 49-Co(II) shows a discrete metal complex with a five-coordinate Co(II) center. 4-9-Co(II) was treated with one equivalent of Ti(IV) isopropoxide in order to rigidify the phenol subunits. The paramagnetic 1H NMR spectra showed noticeable shifting, which indicates that the dinuclea r complex 4-9-Co(II)/Ti(IV) was produced. Unfortunately, attempts to confirm the production of 4-9-Co(II)/Ti (IV) by growing single crystals for X-ray diffraction studies were unsuccessful. Studies with Bulky Metal Salen 2-4a-La(III) CH3CN Designer Lewis acid catalysts, such as steric ally hindered aluminum aryloxides produced by Yamamoto and co-workers128 (Figure 4-15 ) have been developed fo r stereo-, regio-, and chemo-selective carbon-carbon bond-forming reac tions. The steric environment of the aluminum complexes affects the coordination of various oxygen containing substrates. Depending on the aluminum reagent used and th e type of reaction th e carbonyl groups bound to the metal center are either electronically activat ed or sterically deactivated, which leads to selective carbon-carbon bond formation. Specifically, the Lewis Acid catalyst, ATPH (Figure 415), can perform DielsAlder reactions with -unsaturated ketones a nd cyclopentadiene that facilitate a stereochemical re versal in order to produce exo isomers as the major product. The bulky, C3-symmetric Lewis acidic complex, 2-4a -La(III) could also be used to discriminate between structurally and electroni cally similar oxygen functi onalities and then used to facilitate selective organic synthesis. So, metal salen 2-4a-La(III) CH3CN was treated with a variety of oxygen containing orga nic molecules to determine which potential substrates the

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122 Lewis acidic center could bind. Initially, 2-4a-La(III) CH3CN in CD2Cl2 was treated with one equivalent of benzaldeh yde or acetophenone, and the 1H and 13C NMR spectra of the mixtures were monitored for changes that would indicate substrates binding. There were no noticeable changes in the spectra over the course of 48 hours. Thinking that perhaps the metal center was t oo sterically encumbered to bind an oxygen atom so close to a phenyl derivative, the substrate cinnamaldehyde was added to 2-4aLa(III) CH3CN. Once again, the 1H and 13C NMR spectra showed no changes in the signals of the substrate, which led to testing of crotonald ehyde, an aldehyde substrat e that does not contain a phenyl derivative. The data from the 1H and 13C NMR experiments suggest that 2-4aLa(III) CH3CN cannot bind even this small subs trate. Metal salen 2-4a-La(III) THF was not tested for substrate binding, because earlier te sting with this complex had shown that 2-4aLa(III) THF is extremely stable and the coordinate d THF molecule cannot be removed from the metal center. However, when 2-4a-La(III) CH3CN is stirred acetone-d6 for 24 hours, the 1H NMR spectrum shows two sets of residua l acetone signals. One set had the signals know to be residual acetone in acetone-d6 and the other set of signals were co mpletely different, which suggests that the metal center can bind substrates contai ning oxygen atoms. Looking at the solid-state structure of 2-4a-La(III) CH3CN, it appears that the tbutyl substituents may be blocking the substrates access to the Lewis acidic center. For this reason, attempts were made to produce triphenoxymethane salens with less bulky alkyl gr oups in this position, which could then be used to produce the metal complex. Following the general approach for produc ing triphenoxymethane salens, a solution containing three equivalents of 4-6e-h in refluxing absolute ethanol were treated with one

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123 equivalent of Tren (Figure 4-16). The resul ting bright yellow precip itates were the desired ligands 4-10e-h. All triphenoxymetha ne salens were characterized by 1H NMR spectroscopy, and the spectra showed that the Schiff base reac tion converted cleanly gi ving one major product. The reaction conditions produced the triphenoxymeth ane salens in high yields and in multi-gram quantities. Many attempts were made to produce the La(III) salen complexes from the new triphenoxymethane salens; however, all known pr ocedures used to produce similar metal complexes did not produce the desired product. Because, the new Lewis acidic complexes could not be synthesized no further bindi ng studies could be performed. Conclusions Extrem ely bulky and rigid chiral dinuclear me tal salens containing Co(II), Zn(II), and Ti (IV) active metal centers were synthesized. Th e Co(II) and Zn(II) derivatives were able to promote the alkylation of benzaldehyde by diethyl zinc quantitatively. Th e catalyst containing a Co(II) active metal center as well as a Ti(IV) center preferentially produced ( S)-1-phenylpropan1-ol with an enantomeric excess of 44%. For th is transformation, the Co( II) catalyst without the Ti(IV) atom could also produce ( S )-1-phenylpropan-1-ol but at the lower enantomeric excess of 35%. The dinuclear catalysts containing Co(II), Zn(II), and Ti(IV) reacti on centers were also able to facilitate the cycloaddi tion of carbon dioxide to epoxides, producing cyclic carbonates. The chiral dinuclear catalyst containing a Co(II) active site can produce quantitative amounts of propylene carbonate from propylene oxide and CO2. Experimental 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

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124 Varian Cary 50 spectrometer. Elemental analys es and Mass spectrometry were performed at the in-house facilities in the De partment of Chemistry at the University of Florida. All solvents were ACS or HPLC grade and used as purchased. For the reactions perfor med in a dry box, all solvents were dried with a Meyer Solvent Purification system. (-)-( R,R )-11,12-Diamino-9,10dihydro-9,10-ethanoanthracene was synthesized and resolved as previously described. 129 A Hewlett Packard 5890 Series II Gas Chromatogr aph was used to determine the ee values of 1-phenylpropan-1-ol on a Supelco ASTEC Chir al Dex B-PM column. The GC conditions were as follows: detector and injector temperature = 250 C, column head pressure = 12 psi, initial temperature = 70 C, initial time = 1 minute, rate = 2 C /minute, final value = 100 C, final time = 5 minutes, rate A =15 C /minute, final value = 170 C, final time = 5 minutes. The absolute configuration of the product was determined by comparing the retention times of enantiopure 1-phenylpropan-1-ol pu rchased from Sigma Aldrich. A Hewlett Packard 5890 Series II Gas Chromato graph was used to determine the ee values of propylene carbonate and styr ene carbonate on a Supelco Be ta Dex 225 column. The GC conditions, determined by the Dr. Cris Dancel, were as follows: detector and injector temperature = 250 C, column head pressure = 10 psi, initial temperature = 45 C, initial time = 0.20 sec, rate = 25 C /minute, final value = 200 C, final time = 15 minutes. General Procedure for the Synthesis of Compounds 4-6 1 m L aliquots of TFA were added to a mixt ure of 2,6-diformyl-4-a lkylphenol (2-1) and 2,4-alkylphenol (2-2) until th e solids dissolved (for 4-6h), the solution turned bright red (for 46e), or the solution turned bright yellow (4-6f and 4-6g). The solution was stirred for 24 hours. During this time, a solid precipitated from the oily mixture. The solid was washed with a

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125 minimal amount of cold methanol, collected via filtration, and dried to obtain the pure desired product. Compound 4-6e Using 1.00 g (4.85 mmol) of 4-ter t-Butyl-2,6-diformylphenol and 1.48 g (12.13 mmol) of neat 2,4-dimethyl-phenol afforded 1.02 g (49%) of product. The material was obtained by collecting the solid via filtration and washing with cold diethyl ether. 1H NMR [CDCl3] = 11.38 (s, 1H), 9.90 (s, 1H), 7.48 (s, 1H), 7.42 (s, 1H), 6.90 (s, 2H), 6.57 (s, 2H), 6.14 (s, 1H), 2.22 (s, 6H), 2.20 (s, 6H), 1.27 (s, 9H). 13C NMR [CDCl3] = 197.09, 157.05, 149.96, 142.52, 135.70, 130.68, 129.70, 129.52, 128.63, 127.37, 127.13, 124.77, 119.91, 38.02, 34.24, 31.23, 20.88, 16.14. DIP-CI-MS: calcd for C28H32O4 432.2301; found 432.2321 [M]+. Anal. Calc. for C28H32O4: C, 77.75; H, 7.46. Found C, 77.44; H, 7.82. Compound 4-6f Using 0.56 g (3.41 mmol) of 2,6-Difor myl-4 -methylphenol and 1.40 g (8.54 mmol) of 4tert -Butyl-2-methylphenol afforded 1.43 g (88%) of product. 1H NMR [CDCl3] = 11.53 (s, 1H), 9.83 (s, 1H), 7.27 (s, 1H), 7.11 (s, 1H), 7.07 (d, J= 2.1 Hz, 2H), 6.80 (d, J = 2.1 Hz, 2H), 6.13 (s, 1H), 2.28 (s, 3H), 2.22 (s, 6H), 1.22 (s, 18H). 13C NMR [CDCl3] = 196.83, 157.08, 150.02, 143.07, 138.32, 132.43, 130.47, 129.15, 126.93, 126.35, 124.31, 124.28, 120.25, 38.56, 34.19, 31.64, 20.80, 16.59. HRMS: calcd for C31H38O4: 474.2770; found 474.2755 [M]+. Anal. Calc. for C31H38O4: C, 78.45; H, 8.70. Found C, 78.31; H, 8.62. Compound 4-6g Using 0.54 g (2.62 mmol) of 4-ter t-Butyl-2,6-diformylphenol and 1.08 g (6.55 mmol) of neat 4tert-Butyl-2-methylphenol afforded 1.24 g (92%) of product. 1H NMR [DMSO-d6] = 10.99 (s, 1H), 9.90 (s, 1H), 7.49 (s, 1H), 7.13 (s, 1H), 6.83 (s, 2H), 6.59 (s, 1H), 6.56 (s, 1H), 2.05 (s, 6H), 1.06 (s, 9H), 1.01 (s, 18H). 13C NMR [DMSO-d6] = 197.59, 156.45, 150.13,

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126 140.70, 140.21, 134.80, 132.64, 129.71, 127.08, 124.91, 124.07, 123.38, 119.86, 55.05, 35.31, 33.69, 33.49, 31.48, 31.30, 30.82, 17.12. HRMS: calcd for C34H44O4 516.3240; found 516.3265 [M]+. Compound 4-6h Using 1.50 g (7.28 mmol) of 4-ter t-Butyl-2,6-diformylphenol and 2.99 g (18.20 mmol) of 4-methyl-2-tert -Butyl-phenol afforded 2.00 g (53%) of product. 1H NMR [CDCl3] = 11.40 (s, 1H), 9.94 (s, 1H), 7.53 (s, 1H), 7.40 (s, 1H), 7.10 (s, 2H), 6.58 (s, 2H), 5.95 (s, 1H), 2.23 (s, 6H), 1.40 (s, 18H), 1.26 (s, 9H). 13C NMR [CDCl3] = 197.06, 157.01, 151.28, 143.13, 137.91, 135.69, 129.67, 129.10, 129.04, 127.56, 127.38, 126.91, 120.07, 40.02, 34.87, 34.35, 31.28, 29.93, 21.30. HRMS: calcd for C34H44O4 516.3224; found 516.3240 [M]+. General Procedure for the Synthesis of Ch iral Compounds 4-7c/d-M(II/IV)/Ti(IV) A portion of 4-7c/d was dissolv ed in 50 mL of dry methylen e chloride under an inert atmosphere. One equivalent of titanium (IV) isopropoxide was added to solution, which was allowed to stir for 12 hours in a dry box. The solvent was removed in vacuo giving the desired pure product. Chiral Compound 4-7c-Co(II)/Ti(IV) Using 0.60 g (0.46 mmol) of 4-7c-Co(II) and 0 .13 g (0.46 mmol) of Titanium (IV) isopropoxide afforded 0.35 g (57%) of product. Cr ystals suitable for X-ray diffraction were grown by a diffusion of THF/Pentane. Paramagnetic 1H NMR [CD2Cl2] = 23.12, 18.31, 14.47, 11.55, 9.77, 9.28, 8.10, 7.75, 7.21, 6.97, 6.43, 6.18, 4.66, 3.91, 3.55, 2.69, 2.35, 1.86, 1.70, 1.28, 1.18, 0.89, 0.19, -0.83, -4.21, -5.74, -6.13, -9.26, -11.71. MALDI-TOF-MS: calcd for C80H76N4O10CoTi 1359.4367; found 1359.4254 [M]+.

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127 Chiral Compound 4-7c-Zn(II)/Ti(IV) Using 0.88 g (0.66 mmol) of 4-7c-Zn(II) a nd 0 .20 g (0.66 mmol) of Titanium (IV) isopropoxide afforded 0.70 g (78%) of product. Cr ystals suitable for X-ray diffraction were grown by a diffusion of TH F/Pentane. 1H NMR [CD2Cl2] = 10.74 (s, 2H), 10.42 (s, 2H), 10.15 (s, 2H), 9.98 (d, J = 9.0 Hz, 2H), 9.88 (d, J = 9.0 Hz 2H), 9.48 (s, 2H), 9.41 (t, J = 9.0 Hz, 2H), 9.18 (t, J = 9.0 Hz, 2H), 9.08 (s, 2H), 8.97 (d, J = 9.0 Hz, 2H), 8.79 (d, J = 9.0 Hz, 2H), 8.73 (s, 2H), 8.64 (s, 2H), 7.89 (s, 2H), 4.38 (s, 6H), 3.98 (s, 6H), 3.42 (s, 18H), 3.02 (s, 18H). 13C NMR [CD2Cl2] = 160.66, 160.23, 144.61, 140.13, 137.88, 137.65, 136.10, 134.21, 133.95, 132.81, 131.75, 131.69, 128.89, 128.00, 127.57, 126.31, 124.92, 124.00, 121.83, 117.01, 68.46, 54.72, 54.36, 54.00, 53.64, 53.28, 35.99, 35.05, 30.70, 30.13, 25.83, 22.92, 21.60. MALDI-TOF-MS: calcd for C80H76N4O10ZnTi 1366.4374; found 1366.4339 [M]+. Chiral Compound 4-7d-Co(II)/Ti(IV) Using 0.75 g (0.54 mmol) of 4-7d-Co(II) and 0 .15 g (0.54 mmol) of Titanium (IV) isopropoxide afforded 0.61 g (82%) of product. Paramagnetic 1H NMR [CDCl3] = 26.28, 16.77, 13.23, 11.35, 9.58, 8.24, 6.67, 6.49, 6.04, 5.78, 3.22, 3.13, 3.10, 2.82, 1.86, 0.99, -2.20, 2.85, -4.81, -5.47. -9.45. MALDI-TOF-MS: calcd for C80H76Br2N2O6CoTi 1427.2876; found 1427.2801 [M]+. Chiral Compound 4-7d-Ti(IV)/Ti(IV) Using 0.50 g (0.38 mmol) of 4-6d and 0.21 g (0.75 mm ol) of Titanium (IV) isopropoxide afforded 0.41 g (77%) of product. The product was purified by batch crystallization from a toluene/pentane diffusion. 1H NMR [CD2Cl2] = 8.04-7.76 (m, 9H), 7.49-7.04 (m, 24H), 6.836.76 (m, 4H), 6.33 (s, 1H), 6.00 (s, 1H), 5.87 (s, 1H), 5.60 (s, 1H), 5.87 (s, 1H), 3.83 (m, 1H), 3.62 (m, 1H), 2.41 (s, 3H), 2.34 (s, 3H), 2.21 (s, 3H), 2.15 (s, 3H), 1.46 (s, 9H), 1.42 (s, 9H), 1.19 (s, 9H), 1.04 (s, 9H), 0.88 (d, J=6.0 Hz, 3H), 0.62 (d, J=6.0 Hz, 3H), 0.22 (d, J=6.0 Hz, 3H),

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128 -0.50 (d, J=6.0 Hz, 3H). 13C NMR [CD2Cl2] = 165.12, 164.76, 164.44, 163.37, 162.42, 157.64, 156.97, 151.66, 151.27, 149.73, 149.49, 139.46, 138.62, 138.20, 137.87, 137.71, 136.75, 134.45, 134.19, 133.57, 133.49, 133.40, 132.62, 132.49, 132.43, 132.37, 132.32, 132.16, 131.88, 131.63, 130.27, 130.10, 129.97, 129.84, 129.23, 129.08, 129.00, 128.89, 128.55, 128.18, 128.06, 127.95, 127.73, 127.53, 127.47, 127.25, 126.99, 126.75, 126.04, 126.98, 125.46, 123.92, 123.78, 123.60, 122.70, 122.10, 109.29, 108.56, 108.18, 81.40, 80.71, 80.41, 78.86, 76.90, 37.77, 37.31, 36.02, 35.75, 35.51, 35.17, 31.52, 31.04, 30.62, 30.45, 30.15, 27.0, 26.16, 25.94, 25.64 25.44, 22.30, 21.93, 21.76. General Procedure for the Synthesis of Racemic Compounds 4-7c/d The appropriate triphenoxym eth ane aldehyde was added to 150 mL of absolute ethanol and the resulting solution was brought to a reflux. 1,1-Binapthyl-2,2-diamine was added to the refluxing ethanol mixture, which immediately turn ed bright orange. Th e mixture was refluxed for 12 hours. The pure product was collected by filtration (for 4-7d) and dried, or isolated by precipitation with water (for 4-7c), collected via filtr ation, and dried. Racemic Compound 4-7c Using 0.50 g (1.76 mmol) of 1,1-B inapthyl-2,2-d iamine and 1.78 g (3.52 mmol) of 3-(bis(3tert-butyl-2-hydroxy-5-methyl phenyl)methyl)-2-hydroxy-5-nitrobenzaldehyde afforded 1.40 g (63%) of product. 1H NMR [CDCl3] = 14.65 (bs, 2H), 8.71 (s, 2H), 8.14 (m, 4H), 7.99 (m, 2H), 7.93 (d, J = 2.4 Hz, 2H), 7.84 (m, 2H), 7.68 (d, J = 9.0 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 [CDCl3] = 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.

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129 Racemic Compound 4-7d Using 0.50 g (1.76 mmol) of 1,1-B inapthyl-2,2-d iamine and 1.89 g (3.52 mmol) of 3-(bis(3tert-butyl-2-hydroxy-5-methylphenyl)methyl)-5 -bromo-2-hydroxybenzaldehyde afforded 1.60 g (69%) of product. 1H NMR [CDCl3] = 13.42 (s, 2H), 8.51 (s, 2H), 8.11 (d, J = 9.0 Hz, 2H), 7.99 (d, J = 9.0 Hz, 2H), 7.60 (d, J = 9.0 Hz, 2H), 7.49 (t, J = 9.0 Hz, 2H), 7.34 (m, 2H), 7.18 (d, J = 9.0 Hz, 4H), 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 [CDCl3] = 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. Racemic Compound 4-7c-Co(II) Racem ic 4-7c (0.20 g, 0.16 mmol) was added to 50 mL of methanol and the resulting solution was brought to a reflux. A large excess of Co (II) Acetate (0.10 g, 0.56 mmol) was added to the orange mixture, and the solution was allowed to continue to reflux under an inert atmosphere. Within 12 hours a yellow-brown solid formed. Th e product was collected by filtration and dried to obtain 0.08 g of pure product. Yield of 40%. Paramagnetic 1H NMR [CDCl3] = 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. Anal Calc. for C85H88Cl2CoN6O10: C, 68.82; H, 5.98; N, 5.67. Found C, 68.95; H, 6.13; N, 5.40. Racemic compound 4-7d-Co(II) Racem ic 4-7d (0.50g, 0.38mmol) was added to 50 mL of methylene chloride and the resulting solution was brought to a reflux. A portion of Co(II) acetate (0.10 g, 0.56 mmol) in 10 mL of methanol was added to the refluxing orange mixt ure, and the solution was allowed to continue refluxing under an inert atmosphere for 12 hours. The solution was cooled and a bright orange

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130 solid formed. The product was collected by filtration and dried to obtain 0.18 g of pure product. Yield of 35%. Paramagnetic 1H NMR [CDCl3] = 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. Anal Calc. for C84H88Br2CoN2O10: C, 67.07; H, 5.90; N, 1.86. Found C, 67.22; H, 5.68; N, 1.85. Racemic Compound 4-7c-Zn(II) Racem ic 4-7c (0.20 g, 0.16 mmol) was added to 50 mL of methanol and the resulting solution was brought to a reflux. A large excess of Zn (II) acetate (0.10 g, 0.40 mmol) was added to the refluxing yellow mixture, and the solution was allo wed to reflux open to air. Within an hour a yellow solid formed. The product was collected by filtration and dried to obtain 0.12 g of pure product. Yield of 55%. 1H NMR [CDCl3] = 8.44 (s, 2H), 8.07 (m, 6H), 7.97 (d, J = 9.0 Hz, 2H), 7.48 (t, J = 7.5 Hz, 2H), 7.32 (d, J = 9.0 Hz, 2H), 7.00 (s, 4H), 6.90 (d, J = 9.0 Hz, 2H), 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 [CDCl3] = 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. Racemic Compound 4-7d-Zn(II) Racem ic 4-7d (0.50 g, 0.38 mmol) was dissolved in a minimal amount of methylene chloride. The resulting solution was diluted with 100 mL of acetonitrile and warmed to 75 C. A portion of Zn(II) acetate (0.10 g, 0.45 mmol) was added to the refluxing orange mixture. Within 20 minutes a yellow solid formed. The product was collected by filtration a nd dried to obtain 0.44 g of pure product. Yield of 83%. 1H NMR [CDCl3] = 8.28 (s, 2H), 8.03 (d, J = 9.0 Hz, 2H), 7.91(d, J = 9.0 Hz, 2H), 7.45 (t, J = 9.0 Hz, 2H), 7.38-7.36 (m, 4H), 7.23 (t, J =9.0 Hz, 2H), 7.13 (d, J = 3.0 Hz, 2H), 6.97 (s, 4H), 6.90 (d, J = 9.0 Hz 2H), 6.77 (s, 2H), 6.66 (s, 2H), 6.49 (s, 2H),

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131 6.21 (s, 2H), 5.71 (s, 1H), 2.18 (s, 6H), 2.13 (s 6H), 1.37 (s, 18H), 1.24 (s, 18H). 13C NMR [CDCl3] = 165.41, 151.78, 151.68, 144.12, 137.76, 137.62, 137.74, 136.74, 133.66, 132.50, 131.67, 128.84, 128.74, 127.77, 127.38, 126.78, 125.54, 119.78, 107.46, 77.65, 77.23, 35.06, 34.89, 30.07, 29.88, 21.32, 21.24. Anal. Calc. for C82H88Br2N2O8Zn: C, 67.70; H, 6.10; N, 1.93. Found C, 67.53; H, 5.80; N, 1.95. APCI-TOF-MS: calcd for C80H76Br2N2O6Zn 1391.3730; found 1391.3636 [M +H]+. General Procedure for the Synthesis of Racemic Compounds 4-7c/d-M(II)/Ti(IV) A portion of 4-7c/d was dissolv ed in 50 mL of dry methylen e chloride under an inert atmosphere. One equivalent of titanium(IV) is opropoxide was added to the solution, which was allowed to stir for 12 hours in a dry box. The solvent was removed in vacuo giving the desired pure product. Racemic Compound 4-7c-Co(II)/Ti(IV) Using 0.79 g (0.60 mmol) of 4-7c-Co(II) and 0 .17 g (0.60 mmol) of Titanium(IV) isopropoxide afforded 0.58 g (71%) of product. Paramagnetic 1H NMR [CD2Cl2] = 23.12, 18.31, 14.47, 11.55, 9.77, 9.28, 8.10, 7.75, 7.21, 6.97, 6.43, 6.18, 4.66, 3.91, 3.55, 2.69, 2.35, 1.86, 1.70, 1.28, 1.18, 0.89, 0.19, -0.83, -4.21, -5.74, -6.13, -9.26, -11.71. Racemic Compound 4-7c-Zn(II)/Ti(IV) Using 1.00 g (0.76 mmol) of 4-7c-Zn(II) a nd 0 .22 g (0.76 mmol) of Titanium(IV) isopropoxide afforded 0.70 g (68%) of product. 1H NMR [CD2Cl2] = 10.74 (s, 2H), 10.42 (s, 2H), 10.15 (s, 2H), 9.98 (d, J = 9.0 Hz, 2H), 9.88 (d, J = 9.0 Hz, 2H), 9.48 (s, 2H), 9.41 (t, J = 9.0 Hz, 2H), 9.18 (t, J = 9.0 Hz, 2H), 9.08 (s, 2H), 8.97 (d, J = 9.0 Hz, 2H), 8.79 (d, J = 9.0 Hz, 2H), 8.73 (s, 2H), 8.64 (s, 2H), 7.89 (s, 2H), 4.38 (s, 6H), 3.98 (s, 6H), 3.42 (s, 18H), 3.02 (s, 18H). 13C NMR [CD2Cl2] = 160.66, 160.23, 144.61, 140.13, 137.88, 137.65, 136.10, 134.21, 133.95,

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132 132.81, 131.75, 131.69, 128.89, 128.00, 127.57, 126.31, 124.92, 124.00, 121.83, 117.01, 68.46, 54.72, 54.36, 54.00, 53.64, 53.28, 35.99, 35.05, 30.70, 30.13, 25.83, 22.92, 21.60. Racemic Compound 4-7d-Co(II)/Ti(IV) Using 1.00 g (0.72 mmol) of 4-7d-Co(II) and 0 .21 g (0.72 mmol) of Titanium(IV) isopropoxide afforded 0.85 g (83%) of product. Paramagnetic 1H NMR [CD2Cl2] = 26.28, 16.77, 13.23, 11.35, 9.58, 8.24, 6.67, 6.49, 6.04, 5.78, 3.22, 3.13, 3.10, 2.82, 1.86, 0.99, -2.20, -2.85, -4.81, -5.47. -9.45. Racemic Compound 4-7d-Zn(II)/Ti(IV) Using 1.00 g (0.72 mmol) of 4-7d-Co(II) and 0 .21 g (0.72 mmol) of Titanium(IV) isopropoxide afforded 0.75 g (73%) of product. 1H NMR [CD2Cl2] = 10.19 (s, 2H), 9.94 (d, J = 9.0 Hz, 4H), 9.84 (d, J = 9.0 Hz, 4H), 9.44 (s, 2H), 9.35 (t, J = 9.0 Hz, 2H), 9.12 (m, 4H), 9.08 (s, 1H), 9.01 (s, 2H), 8.96 (s, 2H), 8.93 (s, 2H), 8.72 (s, 1H), 8.69 (s, 2H), 8.66 (s, 2H), 7.80 (s, 2H), 4.33 (s, 6H), 4.00 (s, 6H), 3.36 (s, 18H), 2.97 (s, 18H). 13C NMR [CD2Cl2] = 170.73, 160.66, 160.46, 145.12, 140.44, 139.06, 137.69, 135.83, 134.40, 134.36, 132.70, 131.44, 128.77, 127.70, 126.89, 126.53, 126.45, 124.52, 124.05, 121.84, 119.44, 104.88, 54.72, 54.36, 54.00, 53.64, 53.28, 35.94, 34.99, 30.81, 30.78, 30.05, 21.61, 21.48. APCI-TOF-MS: calcd for C80H76Br2N2O6ZnTi 1371.3782; found 1371.3661 [M+H]+. General Procedure for the Addition of Et2Zn to Benzaldehyde In a dry box, the desired catal yst (0.92 mmol) was dissolved in toluene, which was then treated with a solution of ZnEt2 (1.84 mmol) and benzaldehyde (9.2 mmol). The reaction mixture was allowed to stir for 96 hours at room temperature. The mixture was removed from the dry box, diluted with diethyl et her, and treated with a dilute hydrochloric acid solution. The water layer was removed, the resulting solid was filtered, and the remaining ether solution was evaporated to dryness. The remaining oily resi due was washed with methanol producing a solid.

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133 The solid was collected and the methanol solu tion was evaporated to dryness giving the pure desired product. General Procedure for the Cycloaddition of E poxides with Carbon Dioxide All reactions were carried our in a 100 ml st ainless steel pressure reactor charged with catalyst (0.01 mmol), epoxide (100 mmol), co-catalyst ( 0.02 mmol), and 2 ml of dichloromethane. The reaction vessel was removed from the dry box, purged with CO2 three times, and then charged with 500 psi of CO2. An instant drop in pressure was observed when the reaction mixture was stirred. The vessel was con tinually charged with ca rbon dioxide while the reaction mixture stirred until the pressure remain ed at 500 psi, which was then placed behind a blast shield and heated to the appropriate temper ature for the desired amount of time. Once the reaction was complete, the vessel was cooled and the pressure was released. The crude reaction mixture was used for characterization and analysis. General Procedure for the Synthesis of Compounds 4-8 Two equivalents of compound 4-6 was added to 125 m L of absolute ethanol, and the resulting solution was brought to a reflux. A portion of (-)-( R,R )-11,12-Diamino-9,10-dihydro9,10-ethanoanthracene was added to the refluxing ethanol mixtur e, which immediately turned bright yellow. The solution was allowed to reflux open to the air for 12 hours. After the solution was cooled, water was added to the mixture a nd a yellow solid formed. The pure product was collected by filtration and dried. Compound 4-8a Using 2.01 g (4.23 mmol) of 4-6a and 0.50 g (2.12 mm ol) of (-)-( R,R )-11,12-Diamino9,10-dihydro-9,10-ethanoanthracene afforded 2.01 g (86%) of product. 1H NMR [CDCl3] = 13.10 (s, 2H), 8.26 (s, 2H), 7.36-7.34 (m, 4H), 7.287.21 (m, 4H), 7.05 (s, 2H), 7.02 (s, 2H), 6.95 (s, 2H), 6.94 (s, 2H), 6.67 (s, 2H), 6.59 (s, 2H), 5.88(s, 2H), 5.53 (s, 1H), 5.04 (s, 1H), 4.27 (s,

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134 1H), 3.58 (s, 1H), 2.21 (s, 6H), 2.19 (s, 6H), 2.18 (s, 6H), 1.41 (s, 18H), 1.34 (s, 18H). 13C NMR [CDCl3] = 164.98, 156.35, 151.30, 151.142, 140.60, 139.59, 137.96, 137.67, 134.29, 131.24, 129.25, 128.99, 128.56, 128.46, 127.83, 127.67, 127.56, 127.27, 127.11, 127.01, 125.99, 124.26, 118.25, 51.73, 38.13, 35.01, 34.89, 30.01, 29.97, 29.83, 21.39, 21.31, 20.75. ESI-FTICR-MS: calcd for C78H88N2O6H 1149.6715; found 1149.6765 [M+H]+. Compound 4-8b Using 0.99 g (2.54 mmol) of 4-6b and 0.30 g (1.27 mm ol) of (-)-( R,R )-11,12-Diamino9,10-dihydro-9,10-ethanoanthracene afforded 1.12 g (89%) of product. 1H NMR [CDCl3] = 12.94 (s, 2H), 8.24 (s, 2H), 7.35-7.32 (m, 4H), 7.247.17 (m, 4H), 6.95 (s, 2H), 6.92 (s, 2H), 6.89 (s, 2H), 6.85 (s, 2H), 6.63 (s, 2H), 6.56 (s, 2H), 5.99(s, 2H), 4.26 (s, 2H), 3.56 (s, 2H), 2.23 (s, 6H), 2.12 (s, 6H), 2.20 (s, 6H), 2.17 (s, 6H), 2.16 (s, 6H). 13C NMR [CDCl3] = 165.17, 156.18, 150.34, 150.20, 140.77, 139.64, 134.60, 131.02, 130.70, 129.46, 129.38, 128.74, 128.11, 127.46, 127.40, 127.27, 127.20, 126.84, 125.99, 125.40, 125.14, 124.21, 118.24, 51.76, 37.41, 20.98, 20.81, 16.39, 16.30. ESI-TOF-MS: calcd for C66H64N2O6H 981.4837; found 981.4856 [M+H]+. Compound 4-8c Using 1.07g (2.54 mmol) of 4-6c an d 0.25 g (1.06 mmol) of (-)-(R,R)-11,12-Diamino-9,10dihydro-9,10-ethanoanthracene affo rded 0.70 g (55%) of product. 1H NMR [CDCl3] = 13.99 (s, 2H), 8.32 (s, 2H), 8.10 (d, J = 3.0 Hz, 2H), 7.97 (d, J = 2.7Hz, 2H), 7.37-7.33 (m, 4H), 7.28-7.19 (m, 4H), 7.06 (s, 2H), 7.03 (s, 2H), 6.61 (s, 2H), 6.49 (s, 2H), 5.95 (s, 2H), 5.31 (s, 2H), 4.98 (s, 2H), 4.35 (s, 2H), 3.75 (s, 2H), 2.20 (s, 6H), 2.16 (s, 6H), 1.39 (s, 18H), 1.34 (s, 18H).13C NMR [CDCl3] = 160.13, 150.70, 141.54, 137.90, 130.29, 129.18, 127.83, 127.33, 126.78, 126.75, 126.64, 124.86, 116.24, 53.61, 40.16, 34.70, 30.02, 21.24. MALDI-TOF-MS: calcd for C76H82N4O10H 1211.6104; found 1211.6125 [M+H]+.

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135 Compound 4-8d Using 1.14 g (2.12 mmol) of 4-6d and 0.25 g (1.06 mm ol) of (-)-( R,R )-11,12-Diamino-9,10dihydro-9,10-ethanoanthracene affo rded 0.88 g (65%) of product. 1H NMR [CDCl3] = 13.14 (s, 2H), 8.22 (s, 2H), 7.35 (s, 2H), 7.33 (s, 2H) 7.27-7.19 (m, 4H), 7.07 (s, 2H), 7.04 (s, 2H), 6.98 (s, 2H), 6.62 (s, 2H), 6.53 (s, 2H), 5.90 (s, 2H), 5.27 (s, 1H), 4.91 (s, 1H), 4.29 (s, 1H), 3.61 (s, 1H), 2.22 (s, 6H), 2.19 (s, 6H), 1.41 (s, 18H), 1.34 (s, 18H). 13C NMR [CDCl3] = 164.01, 157.76, 151.12, 150.95, 140.39, 139.28, 137.99, 137.77, 136.13, 133.11, 131.94, 129.64, 129.39, 127.53, 127.39, 127.27, 127.10, 126.84, 125.97, 125.73, 124.35, 119.72, 110.92, 51.55, 38.36, 34.95, 34.85, 30.54, 30.03, 29.99, 21.39, 21.30. MALDI-TOF-MS: calcd for C76H82N2O6H 11277.4612; found 1277.4621 [M+H]+. General Procedure for the Synthesis of Compounds 4-8-M(II) Com pound 4-8 was added to 50 mL of methanol and the resulting solution was brought to a reflux. A portion of the desired metal salt was added to the refluxing mixture, which produced a colored precipitate. After the solution was cooled, the solid was collected by filtration and dried to obtain the pu re desired product. Compound (4-8a-Co(II))2 Using 0.25g (0.25 mmol) of 4-8a and 0.06 g (0.28 mmol) of Co(II) acet ate afforded 0.19 g (72%) of green product within 2 hours. Paramagnetic 1H NMR [CDCl3] = 13.57, 9.57, 7.47, 5.46, 4.74, 4.07, 3.59, 2.98, 2.17, 2.10, 1.53, 1.41, 1.34, 0.14, -2.52. ESI-TOF-MS: calcd for C156H172N4O12Co2H 2413.1742; found 2413.1850 [M+H]+. Compound (4-8a-Fe(II))2 Using 0.27g (0.23 mmol) of 4-8b and 0.12 g (0.26 mmol) of Fe(II) acetate afforded 0.04 g (42%) of purple product within 24 hours. APCI-TOF-MS: calcd for C156H172N4O12Fe2 2406.1705; found 2406.1652 [M]+.

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136 Compound (4-8b-Zn(II))2 Using 0.50g (0.51 mmol) of 4-8b and 0.12 g (0.56 mmol) of Zn(II)acetate afforded 0.30 g (57%) of yellow product within 10 minutes. Crystals suitable for X-ray diffraction were grown by a diffusion of CH3CN/Methanol. 1H NMR [CDCl3] = 8.15 (s, 4H), 7.27 (t, 4H), 7.10 (d, 4H), 7.05 (s, 4H), 6.98 (t, 4H), 6.92 (d, 4H), 6.72 (m, 12H), 6.39 (s, 4H), 6.02 (s, 6H), 5.88 (s, 2H), 4.81 (s, 4H), 4.45 (s, 4H), 3.46 (s, 4H), 2.13 (s, 12H), 2.06 (s, 12H), 1.95 (s, 12H), 1.91 (s, 12H), 1.58 (s, 12H). 13C NMR [CDCl3] = 169.09, 163.10, 150.98, 150.82, 141.83, 138.45, 138.15, 135.18, 132.08, 130.32, 130.17, 129.13, 128.75, 128.08, 127.64, 127.36, 126.70, 126.19, 125.63, 125.12, 125.00, 124.84, 117.83 49.03, 35.85, 21.03, 20.87, 19.68, 17.31, 16.13. ESITOF-MS: calcd for C132H124N4O12Zn2 2111.7699; found 2111.7446 [M+Na]+. Compound (4-8b-Co(II))2 Using 0.25g (0.25 mmol) of 4-8b and 0.07 g (0.28 mmol) of Co(II)acetate refluxed in an inert atmosphere afforded 0.14 g (53%) of product within 10 minutes. Paramagnetic 1H NMR [CDCl3] = 57.55, 37.09, 12.50, 12.47, 8.97, 7.80, 5.36, 4.28, 4.16, 3.80, 2.21, 2.11, 1.23, 0.93, 0.03, 0.17, -2.16. MALDI-TOF-MS: calcd for C132H124N4O12Co2H 2075.7952; found 2075.7779 [M+H]+. General Procedure for the Synthesis of Compounds 4-9 Two equivalents of compound 4-6 was added to 125 m L of absolute ethanol, and the resulting solution was brought to a reflux. A portion of meso -1,2-Diphenylethylenediamine was added to the refluxing ethanol mixture, which immediately turned bright yellow. A yellow solid formed within an hour, but the solution was allowe d to reflux open to the air for a total of 12 hours. After the solution was cooled, the product was collected by filtration and dried to obtain the pure desired product.

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137 Compound 4-9a Using 2.24g (4.71 mmol) of 4-6a and 0.50 g (2.40 mm ol) of meso-1,2-Diphenylethylenediamine afforded 2.52 g (93%) of product. 1H NMR [CDCl3] = 13.95 (s, 2H), 7.94 (s, 2H), 7.26 (m, 10H), 7.05 (s, 2H), 7.03 (s, 2H), 6.94 (s, 2H), 6.78 (s, 2H ), 6.66 (s, 2H), 6.64 (s, 2H), 5.92 (s, 2H), 5.62(s, 2H), 5.21 (s, 2H), 4.69 (s, 2H), 2.21 (s, 6H), 2.18 (s, 6H), 2.15 (s, 16H), 1.40 (s, 18H), 1.27 (s, 18H). 13C NMR [CDCl3] = 156.36, 151.56, 151.45, 137.80, 131.34, 129.28, 129.14, 128.95, 128.43, 128.26, 128.12, 127.69, 127.50, 127.27, 118.29, 100.12, 79.94, 35.03, 34.95, 29.98, 21.35, 20.77, 20.51. ESI-TOF-MS: calcd for C76H88N2O6Na 1147.6535; found 1147.6531 [M+Na]+. Compound 4-9b Using 0.92g (2.35 mmol) of 4-6b and 0.25 g (1.18 mm ol) of meso -1,2-Diphenylethylenediamine afforded 0.94 g (83%) of product. 1H NMR [pyridine-d5] = 13.58 (s, 2H), 7.99 (s, 2H), 7.55 (s, 2H), 7.29-7.08 (m, 10H), 76.96 (s, 2H), 6.88 (s, 2H), 6.69 (s, 2H), 4.66 (s, 2H), 2.44 (s, 6H), 2.37 (s, 6H), 2.20 (s, 6H), 2.12 (s, H), 2.05 (s, 6H), 1.88 (s, 6H). 13C NMR [pyridine-d5] = 167.12, 158.04, 152.66, 152.54, 141.14, 134.89, 134.00, 133.34, 132.96, 130.76, 130.44, 130.34, 129.27, 129.12, 128.98, 128.91, 128.74, 127.33, 126.44, 126.29, 118.82, 80.94, 39.42, 21.44, 21.30, 20.82, 17.91. ESI-FT-ICR-MS: calcd for C64H64N2O6H 957.4837; found 957.4839 [M+H]+. Compound 4-9f Using 1.12g (2.35 mmol) of 4-6e and 0.25 g (1.18 mm ol) of meso -1,2-Diphenylethylenediamine afforded 1.24 g (89%) of product. 1H NMR [CDCl3] = 13.81 (bs, 2H), 7.95 (s, 2H), 7.27-7.20 (m, 10H), 7.08 (s, 2H), 7.05 (s, 2H), 6.94 (s, 2H), 6.90 (s, 2H), 6.88 (s, 2H), 6.77 (s, 2H), 6.06 (s, 2H), 5.52(bs, 2H), 5.22 (bs, 2H), 4.68 (s, 2H), 2.26 (s, 6H), 2.21 (s, 6H), 2.15 (s, 6H), 1.20 (s, 18H), 1.16 (s, 18H). 13C NMR [CDCl3] = 166.13, 156.35, 150.53, 142.93, 142.84,

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138 139.45, 134.33, 131.03, 128.90, 128.17, 126.88, 126.73, 126.28, 124.88, 124.43, 123.92, 118.21, 79.85, 38.82, 34.26, 31.75, 31.71, 20.79, 16.85, 16.76. ESI-TOF-MS: calcd for C76H88N2O6Na 1147.6535; found 1147.6516 [M+Na]+. Synthesis of Compound 4-9f-Co(II) Co(II) Acetate (0.10g, 0 .38 mmol) was heated until the metal salt di ssolved in 5ml of absolute ethanol. The solution was heated furthe r until a precipitate formed. The suspension of metal salt was added to a solution of 4-9e (0.43g, 0.38 mmol) in 5ml of absolute ethanol that was heated to 60C. The resulting colored solution was heated for 1 hour under an inert atmosphere, which produced a brown solid. Af ter the solution was cooled, th e precipitate was collected by filtration and dried to obtain 0.41g (92%) of the pure desired product. Paramagnetic 1H NMR [CDCl3] = 24.47, 12.20, 10.03, 9.34, 8.74, 8.34, 5.16, 4.44, 2.26, 1.89, 1.23, -0.13, -0.55, -2.30, -3.85. MALDI-TOF-MS: calcd for C76H86N2O6Co 1182.5891; found 1182.6008 [M]+. General Procedure for the Synthesis of Compounds 4-10 Com pound 4-6 was added to 250 mL of absolute ethanol. The resulting solution was brought to a reflux. A solution of tris(2-aminoethyl)amine (Tren) (5 ml of absolute ethanol) was added to the refluxing ethanol mixture, which immediately turned bright yellow. The mixture was refluxed for 12 hours. The pure product was colle cted by filtration (for 4-10f) and dried, or isolated by precipitation with wa ter (for 4-10e/g/h), collected via filtration, and dried. Compound 4-10e Using 1.00 g (2.31 mmol) of com pound 4-6e a nd 0.11 g (0.77 mmol) of Tren afforded 1.01 g (94%) of product. 1H NMR [CDCl3] = 8.03 (s, 3H), 7.31 (s, 3H), 6.82 (s, 6H), 6.73 (s, 6H), 5.97 (s, 3H), 3.60 (s, 6H), 2.91 (s, 6H), 2.14 (s, 18H), 1.07 (s, 27H). 13C NMR [CDCl3] = 166.56, 150.86, 139.36, 133.36, 130.53, 129.09, 127.55, 127.02, 125.64, 116.22, 33.98, 31.28, 20.98, 16.53. ESI-TOF-MS: calcd for C90H109N4O9 1389.8189; found 1389.8148 [M+H]+.

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139 Compound 4-10f Using 1.00 g (2.11 mmol) of com pound 4-6f a nd 0.10 g (0.70 mmol) of Tren afforded 1.00 g (89%) of product. 1H NMR [CDCl3] = 7.06 (s, 3H), 7.03 (s, 3H), 6.98 (s, 6H), 6.02 (s, 6H), 4.97 (s, 3H), 3.50 (s, 6H), 2.87 (s, 6H), 2.13 (s, 18H), 1.14 (s, 27H). 13C NMR [pyridine-d5] = 168.02, 158.59, 139.36, 133.36, 152.59, 141.83, 134.97, 132.79, 132.01, 126.77, 126.29, 125.87, 125.17, 118.89, 58.38, 56.39, 38.13, 34.68, 32.33, 20.78, 18.40. ESI-TOF-MS: calcd for C99H127N4O9Na 1516.9631; found 1516.9601 [M+H]+. Anal. Calc. for C99H126N4O9: C, 78.43; H, 8.38; N, 3.70. Found C, 78.14; H, 8.57; N, 3.67. Compound 4-10g Using 1.00 g (1.93 mmol) of com pound 4-6g and 0.09 g (0.65mmol) of Tren afforded 0.62 g (58%) of product. 1H NMR [CDCl3] = 8.22 (s, 3H), 7.36 (s, 3H), 7.35 (s, 3H), 6.99 (s, 6H), 6.90 (s, 3H), 6.88 (s, 3H), 6.22 (s, 3H) 3.63 (s, 6H ), 2.94 (s, 6H), 2.16 (s, 9H), 1.18 (s, 27H), 1.08 (s, 27H). 13C NMR [CDCl3] = 150.59, 142.47, 127.21, 126.47, 124.95, 124.16, 34.20, 31.79, 31.34, 16.90. MALDI-TOF-MS: calcd for C108H144N4O9H 1642.1006; found 1642.1049 [M+H]+. Compound 4-10h Using 1.00 g (1.94 mmol) of com pound 4-6h and 0.09 g (0.65mmol) of Tren afforded 0.96 g (91%) of product. 1H NMR [CDCl3] = 8.14 (s, 3H), 7.25 (s, 3H), 6.99 (s, 6H), 6.92 (s, 3H), 6.70 (s, 6H), 5.92 (s, 6H), 3.60 (s, 6H), 2.92 (s, 6H), 2.17 (s, 9H), 1.34 (s, 54H), 1.08 (s, 27H). 13C NMR [CD2Cl2] = 166.75, 151.85, 138.16, 129.35, 128.51, 128.12, 127.09, 116.72, 35.18, 34.29, 31.36, 30.13, 29.86, 21.36. ESI-TOF-MS: calcd for C108H145N4O9 1643.1039; found 1643.0970 [M+H]+. Anal. Calc. for C108H144N4O9: C, 78.98; H, 8.84; N, 3.41. Found C, 78.65; H, 9.19; N, 3.56.

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140 Figure 4-1. Illustration of the metal salen complex known as Jacobsens catalyst. Figure 4-2. Illustration of the enantioselective addition of Et2Zn to benzealdehyde. The chiral Schiff base Zn(II) complex is produced in situ Figure 4-3. Illustration of the axia lly chiral Schiff base ligand used to make bimetallic catalysts.

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141 Figure 4-4. Depiction of two pa thways envisioned for the formation of chiral carbonates via intramolecular cyclic elimination. Figure 4-5. Illustration of the general scheme for the enantiosp ecific addition of carbon dioxide to an epoxide.

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142 Figure 4-6. Illustration of BINA D Co(III) complexes used for the asymmetric cycloaddition of carbon dioxide with epoxides. Figure 4-7. Solid-state structure of a chir al Ni(II)-triphenoxymethane salen made with R,R -1,2diaminocyclohexane.

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143 Figure 4-8. Illustration of the s ynthetic scheme used to make th e four derivatives of the BINAM triphenoxymethane salens. (i ) ethanol, reflux, 24 hours. Figure 4-9. Solid-state stru cture of binuclear BINAM salen 4-7a-Zn(II)/Ti(IV).

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144 Figure 4-10. Synthetic scheme for the production of the chiral dinuclear catalysts 4-7c/dM(II)/Ti(IV). (i) Titanium isopropoxide, inert atmosphere, 12 hours. Figure 4.11. The solid-state structure of 4-7c-C o(II)/Ti(IV) (30% probability; carbon atoms depicted with arbitrary radii). The hydrogen atoms are omitted for clarity.

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145 Figure 4-12. Illustration of the synthetic scheme used to make the triphenoxymethane salens with (-)-( R,R )-11,12-Diamino-9,10-dihydro-9,10-etha noanthracene (i) ethanol, reflux, 24 hours. Figure 4-13. Depiction of the s ynthetic scheme used to make th e triphenoxymethane salens with meso -1,2-Diphenylethylenediamine. (i) ethanol, reflux, 24 hours.

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146 Figure 4-14. Illustration of the synthetic route used to produced (4-8a/b-M(II))2. (i) M(II) Acetate, refluxing methanol, the time vari ed between 10 minutes and 24 hours. Figure 4-15. Illustration of bulky designer Lewi s acid catalysts used in selective carbon-carbon bond-forming reactions.

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147 Figure 4-16. Illustration of Schiff base reaction used to produce Tren triphenoxymethane salens. (i) refluxing absolute ethanol, 12 hours. Table 4-1. CO2 coupling reactions with racemic propyl ene oxide and chir al catalyst 4-3. Catalyst Mol % Co-catalyst CO2 (atm) Time/Temp ee/yield (%) 4-3a 121 X=OTs 0.001 n-Bu4NCl 6.8 15h/0 C 70.2/40.0 4-3b100 X= pMeC6H4SO3 0.001 PTATa 6.8 10h/-5 C 48.7/43.1 4-3c101 0.0005 KOH 5.0 3h/25C 83.7/23.6 4-3d 122 X=OCOCF3 0.10 PPNF b 1.0 18h/-20 C 83.0/40.0 a P-benzyltriphenylphosphonium tribromide. b bis-(triphenylphosphor anylidene)ammonium fluoride.

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148 Table 4-2. Asymmetric addition of ZnEt2 to Benzaldehyde in 96 hours. Catalyst Mol % Conversion (%) %EE Conformation 4-7c-Co(II) 10.0 99.9 2.8 R 4-7c-Co(II)/Ti(IV) 10.0 99.9 10.5 S 4-7c-Zn(II) 10.0 99.9 24.6 R 4-7c-Zn(II)/Ti(IV) 10.0 99.9 1.8 S 4-7d-Co(II) 10.0 99.9 34.7 S 4-7d-Co(II)/Ti(IV) 10.0 99.9 44.5 S Table 4-3. The effect of co-catalyst, temper ature, and time on the formation of propylene carbonate from propylene oxide and CO2 at 500 psi. Catalyst Mol % Co-catalyst Temp ( C)/ Time (h) Conversion (%) 4-7d-Co(II)/Ti(IV) 0.1 TEAa100/48 33 4-7d-Co(II) 0.1 TEA 100/48 0 4-7d-Co(II)/Ti(IV) 0.1 DMAP b 100/48 100 4-7d-Co(II) 0.1 DMAP 100/48 100 4-7d-Co(II)/Ti(IV) 0.05 DMAP 100/48 66 4-7d-Co(II)/Ti(IV) 0.1 DMAP 100/24 35 4-7d-Co(II)/Ti(IV) 10.0 DMAP 35/72 0 4-7d-Co(II)/Ti(IV) 10.0 DMAP 70/48 3 4-7d-Co(II) 10.0 DMAP 100/48 5 a Triethylamine. b 4-Dimethylaminopyridine. Table 4-4. The cycloaddition of CO2 and various epoxides with 4-7d-Co(II)/Ti(IV) and 4-7dCo(II) at 500 psi. Catalyst Epoxide Mol % Co-catalyst Temp ( C)/ Time (h) Conversion (%) ee (%) 4-7d Co(II)/Ti(IV) POa 0.1 DMAP 100/48 100/0 4-7d Co(II) PO 0.1 DMAP 100/48 100/0 4-7d Co(II)/Ti(IV) ( S)-PO 0.1 DMAP 100/48 55/99 4-7d Co(II)/Ti(IV) ( R )-PO 0.1 DMAP 100/48 57/99 4-7d Co(II)/Ti(IV) SO b 0.1 DMAP 100/48 33/0 a Propylene oxide. b Styrene oxide. Table 4-5. The cycloaddition of CO2 and Propylene oxide with 4-7d-Zn(II)/Ti(IV) and 4-7dTi(IV)/Ti(IV) at 500 psi. Catalyst Mol % Co-catalyst Temp ( C)/ Time (h) Conversion (%) 4-7d Zn(II)/Ti(IV) 0.1 DMAP 100/48 37/4-7d Ti(IV)/Ti(IV) 0.1 DMAP 100/48 100/0

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149 Table 4-6. Crystallogra phic data for compound 4-7c-Co(II)/Ti(IV). 4-7c-Co(II)/Ti(IV) 2THF Formula Crystal System Space Group Z a () b () c () ( ) ( ) ( ) Vc (3) Uniq. data coll./obs. R1[ I 2 (I)data] wR2[ I 2 (I)data] C92H92N4O13CoTi Orthorhombic P2(1)2(1)2(1) 4 13.156(2) 23.772(4) 25.600(4) 90.00 90.00 90.00 8007(2) 19135/14111 0.0745 0.1033

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150 LIST OF REFERENCES 1. Bianchi, A.; Bowm an James, K.; Garca Espaa, E. In The supramolecular chemistry of anions; John Wiley: New York, 1997; pp 45-63. 2. Adams, R. L. P.; Knowler, J. T.; Leader, D. P. In The biochemistry of the nucleic acids; Chapman & Hall: London ; New York, 1986; pp 526. 3. American Chemical Society Division of Carbohydrate Chemistry; American Chemical Society Division of Medicinal Chemistry; Am erican Chemical Society Meeting; Martin, J. C. In Nucleotide analogues as antiviral agents; ACS symposium series ; 401; American Chemical Society: Washington, D.C., 1989; pp 190. 4. Furman, P. A.; Fyfe, J. A.; St. Clair, M. H. ; Weinhold, K.; Rideout, J. L.; Freeman, G. A.; Lehrman, S. N.; Bolgnesi, D. P.; Broder, S.; Mitsuya, H.; Barry, D. W. Proc. Natl. Acad Sci. U. S. A. 1986, 83, 8333. 5. Davis, P. B. N. Engl. J. Med. 1991, 325, 575. 6. Quinton, P. M. FASEB 1990, 4, 2709. 7. Bianchi, A.; Bowman James, K.; Garca Espaa, E. In The supramolecular chemistry of anions; John Wiley: New York, 1997; pp 355-403. 8. Kaufmann, D.; Otten, A. Angew. Chem. Int. Ed. Engl. 1994, 33, 1832. 9. Sessler, J. L.; Furata, H.; Kral, V. Supramol. Chem. 1993, 1, 209. 10. Hosseini, M. W.; Lehn, J. -. Helv. Chim. Acta 1987, 70, 1312. 11. Dietrich, B. Pure Appl. Chem. 1993, 7, 1457. 12. Atwood, J. L.; Davies, J. E. D.; MacNicol, D. D. In Inclusion compounds; Oxford science publications. Academic Press: L ondon ; Orlando, 1984; Vol. 2, pp 373-405. 13. Park, C. H.; Simmons, H. E. J. Am. Chem. Soc. 1968, 90, 2431-2432. 14. Beli, R. A.; Christoph, G. G.; Fronczek, F. R.; Marsh, R. E. Science 1975 190, 151-152. 15. Simmons, H. E.; Park, C. H.; Uyeda, R. T.; Habibi, M. F. Trans. New York Acad. Sci. 1970, 32, 521. 16. Dietrich, B.; Guihem J.; Lehn, J. -.; Pascard, C.; Sonveaux, E. Helv. Chim. Acta 1984, 67, 91. 17. Bianchi, A.; Bowman James, K.; Garca Espaa, E. In The supramolecular chemistry of anions; John Wiley: New York, 1997; pp 147-209.

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157 BIOGRAPHICAL SKETCH Candace Zieleniuk was b orn in Mountain Home, Arkansas in 1981. As a child she was fascinated by the world around her. Because she lived, as she likes to call it, in the middle of nowhere, Candace learned about the intriguing plan ts, animals, and cultures of the world from books and television. The battles raged in her household as she fought with her three younger sisters for the right to watch the Public Broadcas ting Service or the Discovery channel. At that time, when it was actually a science-based channe l, The Learning Channel was not available in her small town, to her utter dismay. It was not until the fifth grade, when science was first taught in the Mountain Home school system, that she knew she wanted to do something in science when she grew up. Naturally at her age, the popular answer to this age-old question was, I want to be a doctor. For Candace this choice seemed natural, growing up in house with a nurse and a paramedic for parents. In eleventh grade, Candace took Chemistry from Mr. Smith and discovered that she loved the beauty and, at that time, the simplicity of chemistry. Much to her mothers dismay, Candace abandoned her childhood dream of becoming a doctor and enrolled at the University of Arkansas in the fall of 1999 as a chemistry major. After going back to Mountain Home for the su mmer after her freshman year to earn money babysitting, she decided to spend her future summer s gaining valuable research experience. In the summer of 2001, Candace went to Harvey Mudd College in Claremont, California to work in the experimental physical chemistry lab of Dr. Keri Kaurkstis through the National Science Foundation-Research Experience for Undergraduates (NSF-REU) program. Even though she thoroughly enjoyed her summer work ing in this lab, it was here sh e discovered that she would most likely prefer synt hesis-based research.

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158 When Candace returned to the University of Arkansas that fall, she joined a synthetic group headed by Dr. Neil Allison. That school year she began to learn the many trials and tribulations associated with synthetic chemistry, but she loved the challenge. In the summer of 2002, Candace decided to apply once again to th e NSF-REU program and chose to attend the program at the University of Florida. Here is where she met her future graduate advisor, Dr. Michael Scott. That summer she worked with now Dr. Ivana Bozidarevic on synthesizing metalloporphyrins and porphodimethenes. When sh e left UF that summer, she knew that she wanted to go to graduate school and sh e wanted to be an Inorganic chemist. Before coming to the University of Florida for graduate school, Candace finished her research with Dr. Neil Allison, defended her bachel ors thesis, won the Howard Hantz research award, and graduated Su mma Cum Laude. She came to the University of Florida chemistry department as most first year graduate students are: overly optimistic and enthusiastic. Over, the past six years she has learned that dedication, a little luck, and pure st ubbornness are needed to be a synthetic chemist. Upon the completion of her doctorate, Candace will return to the University of Arkansas Department of Chem istry and Biochemistry as the Director of Undergraduate Labs and as a Research Scientist.