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Structural studies of 4 + 2 perhalocyclopropene cycloadducts

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Title:
Structural studies of 4 + 2 perhalocyclopropene cycloadducts
Creator:
Posey, Robert Giles, 1947-
Copyright Date:
1975
Language:
English
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viii, 147 leaves : ill. ; 28cm.

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Subjects / Keywords:
Absorption spectra ( jstor )
Adducts ( jstor )
Chemical equilibrium ( jstor )
Cyclopentanes ( jstor )
Flasks ( jstor )
Furans ( jstor )
Infrared spectrum ( jstor )
Pentanes ( jstor )
Protons ( jstor )
Stereochemistry ( jstor )
Chemistry thesis Ph. D
Cyclopropenes ( lcsh )
Dissertations, Academic -- Chemistry -- UF
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bibliography ( marcgt )
non-fiction ( marcgt )

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Thesis:
Thesis--University of Florida.
Bibliography:
Bibliography: leaves 142-146.
General Note:
Typescript.
General Note:
Vita.
Statement of Responsibility:
by Robert Giles Posey.

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STRUCTURAL STUDIES OF [4 + 2]
PERHALOCYCLOPROPENE CYCLOADDUCTS












By

ROBERT GILES POSEY


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












UNIVERSITY OF FLORIDA


1975



























To Phyllis and Will















ACKNOWLEDGEMENTS


The author wishes to thank Professor Merle A. Battiste

for directing this research, and for his continued interest

in and support of a research project which became a

learning experience for all concerned. Dr. Battiste is to

be commended for displaying the intellectual flexibility

so vital in the pursuance of research. The author also

wishes to thank the rest of his supervisory committee for

their part in the course of this work, and especially for

their cooperation during the weeks in which this dissertation

was prepared. Appreciation is also expressed to Dr. Wallace

Brey and the members of his research group for their help

in obtaining some of the data used in this study. Also,

partial financial support from the Department of Chemistry

in the form of teaching assistantships was appreciated.

Finally, the author's family deserve special thanks for

providing unfailing support and encouragement throughout

this project.
















TABLE OF CONTENTS


Page

ACKNOWLEDGEMENTS.. ............... ..................... iii

LIST OF TABLES ................................ ...... v

ABSTRACT.... ......................................... vi

CHAPTER I INTRODUCTION......................... ........ 1

Diels-Alder Reactions General......... 1

Alkyl- and Aryl-Cyclopropenes as
Dienophiles........................... 5

Halocyclopropenes as Dienophiles........ 12

Objectives of This Work................. 31

CHAPTER II RESULTS AND DISCUSSION................... 34

Stereochemical Studies of Perhalo-
cyclopropene [4 + 2] Cycloadducts.... 34

Carbene Additions to the Bicyclo-
[2.2.1]-heptyl System................ 73

Isomerization Studies of Selected
[4 + 2] Cycloadducts ................. 80

Synthetic Studies of 3,3-Difluoro-
cyclopropene.......................... 83

CHAPTER III EXPERIMENTAL............................ 98

General .............................. 98

REFERENCES ..................... .................... 142

BIOGRAPHICAL SKETCH................... ... .............. 147
















LIST OF TABLES


1H and 19F

1H and 19F

1H and 19F

1H and 19F

1H and 19F

Comparison
34 and 41..

Comparison

Comparison

11 nmr and


Page

nmr Data for 21 and 22............... 18

nmr Data for 21a .................... 20

nmr Data for 22a..................... 21

nmr Data for 26, 27, and 28........... 24

nmr Data for 27a and 28a.............. 28

of Eu(FOD)3 nmr Shift Results for
.......... ........................... 49

of 19F nmr Chemical Shift Data....... 59
19
of 1F nmr Chemical Shift Data........ 68

1F nmr Data......................... 87


Table

I

II

III

IV



VI


VII

VIII

IX















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



STRUCTURAL STUDIES OF [4 + 2]
PERHALOCYCLOPROPENE CYCLOADDUCTS

By

Robert Giles Posey

December, 1975



Chairman: Dr. Merle A. Battiste
Major Department: Chemistry



Previous literature reports of exclusive formation of

endo [4 + 2] cycloadducts of perhalocyclopropenes with furan

were shown to be in error by a single crystal X-ray structural

analysis of the phenyl azide adduct 32 of 2,4-dibromo-3,3-

difluoro-8-oxatricyclo[3.2.1.02'4]oct-6-ene (20a), which

revealed the exo stereochemistry of the gem-difluorocyclo-

propane ring in 32, and thus in 20a. Using exo-20a as a

model compound, a series of chemical transformations were

carried out in order to establish H nmr and 19F nmr param-

eters to be used for the determination of stereochemistry in

unknown systems. In addition, heteronuclear decoupling,

measurements of line widths at half-height (W1/2), and

Eu(FOD)3 nmr shift experiments were carried out on 20a and









the series of compounds derived from 20a, of which all

were known to possess exo stereochemistry.

New [4 + 2] cycloadducts of 1,2-dibromo-3,3-difluoro-

cyclopropene (15) were prepared with 1,3-diphenylisobenzo-

furan, isobenzofuran, 6,6-diphenylfulvene, 6,6-dimethyl-

fulvene, spiro[4.2 heptadiene, cyclopentadiene, and the

acyclic diene l-methoxy-l,3-butadiene. By the application

of chemical transformations as well as the spectroscopic

techniques previously mentioned, it was shown that under

the reaction conditions used, the cyclic dienes formed

exclusively exo [4 + 2] adducts with 15 as isolated products.

In the adducts of 15 with cyclopentadiene and spiro-
19
[4.2]heptadiene (63 and 57a), substantial long range F -
iH coupling was observed in the H and 19F mr spectra,

and this phenomenon was part of the evidence used for the

assignment of exo stereochemistry in these compounds. This

5 FH and 6JFH coupling was compared with previous literature

reports, and in the case of the spiro[4.2]heptadiene adduct

(57a) constitutes the first example of the intercalated

mode of long range 1F H coupling.

Having established the exo stereochemistry for the

[4 + 2] cycloadducts of 15 formed at relatively high tem-

peratures (800 115 C), the behavior of adduct 20a was

examined at various temperatures. As a result, it was found

that only exo-20a was formed at lower temperatures, but that

at 750 800 C, an equilibrium mixture of exo-20a and endo-20

could be detected by 19F nmr. The adduct of 15 with iso-








19
benzofuran was found by 19F nmr to retain the original

exo orientation after prolonged heating at 800 C.

As part of the attempted synthesis of the epimeric

exo (54)- and endo (55)-3,3-difluorotricyclo[3.2.1.02'4]-

octan-8-ones, the synthesis of the previously unknown

3,3-difluorocyclopropene (87) was attempted. In one such

attempt, the product of the reaction of 15 with anthracene

at 1300 C was shown to be a ring opened species. In another

attempt at the preparation of 87, the unstable 1,2-bis-

(trimethylsilyl)3,3-difluorocyclopropene (86) was prepared,

but the attempted conversion of 86 to 87 by hydrolysis

failed to give any volatile products.


viii














CHAPTER I


INTRODUCTION


Diels-Alder Reactions General


Reactions between conjugated dienes and olefins have

been thoroughly investigated and have become quite impor-

tant synthetic tools in organic chemistry.1 The reaction

products are either mono-, bi-, or tri-cyclic, depending

on whether the diene and/or dienophile are cyclic or acyclic,

as shown below.



+




+ -






+



Such reactions were first extensively utilized by Diels

and Alder, beginning in 1928, and since then the mechanistic

aspects of the Diels-Alder reaction have been probed by a

number of workers. Various effects of substituents,









catalysts, and solvents as well as steric and electronic

factors were reviewed by Seltzer. Of course, the Diels-

Alder reaction may be viewed in terms of the Woodward-

Hoffmann orbital symmetry treatment.4 As illustrated in

the following correlation diagram, Diels-Alder cyclo-

additions are thermally allowed processes, with the like-

lihood of reaction and structure of products controlled by

substituents on both the diene and the dienophile.

A4 3 4


-+-+ 0 A--

+- 7" A -A 7

-++- 3 S-_



++-- 0 A---

++ S--

++++ 01 S-I---


AS2 1 0a1 A G 2


In those Diels-Alder reactions where the possibility

of stereoisomerism exists, predetermination of reaction

product stereochemistry is not always as simple as merely

applying the Alder endo rule.5 This rule states that the

reacting species, when arranged in parallel planes, will

react via the orientation which has the "maximum accumula-

tion" of double bonds, which includes all double bonds in







both the diene and the dienophile. The endo-addition rule
is illustrated below for the reaction of maleic anhydride
with cyclopentadiene, which proceeds to give> 98.5% endo-
adduct and <1.5% exo-adduct. Indeed, the majority of





H H

<1.5% >98.5%


cycloadditions between cyclic dienes and cyclic dienophiles
obey the endo-addition rule. However, the endo-addition
rule is applicable to kinetically controlled phenomena,
and does not necessarily reflect the relative thermodynamic
stabilities of stereoisomeric products. In the example
shown below, the endo-adduct of furan and succinimide
isomerizes upon warming to the more thermodynamically stable
exo isomer. Analagous behavior, i.e., facile cycloreversion



+ 250 9g0
H H K 1 H
H t


of the endo isomer followed by addition to give the









thermodynamically preferred exo isomer has also been re-

ported for adducts of fulvenes.

The question of mechanistic pathways for endo/exo

isomerizations of Diels-Alder adducts has been examined

in a variety of diene/dienophile systems, and several

possible mechanisms have been proposed for observed endo

to exo isomerizations. The first of these possibilities,

and the one most universally applicable is a retro-Diels-

Alder reaction followed by subsequent recombination to form

the thermodynamically more stable product. However, in

some systems intramolecular endo to exo isomerizations can

occur by a one bond cleavage-hydrogen shift mechanism.9



H

H H H

H H






10
A third mechanism formulated by Berson et al., for the

isomerization depicted above is a process involving dis-

sociation of the endo adduct to the endo-addition complex,

which through rotation isomerizes to the exo-addition

complex, followed by rapid recombination to give a net

"internal" isomerization. However, this mechanism has not

been firmly established, and has been challenged by other
authors.11 Also, Berson and his co-workers attempted to
authors. Also, Berson and his co-workers attempted to









obtain evidence for their internal isomerization mechanism

in two other systems,12,13,14 but the data obtained best

support the retro-Diels-Alder-recyclization mechanism.


Alkyl- and Aryl-Cyclopropenes as Dienophiles


A special case of the Diels-Alder reaction involves

utilization of cyclopropenes as dienophiles. Cyclopropene

itself reacts at 00 C with cyclopentadiene to form only

endo-tricyclo[3.2.1.02'4]oct-6-ene.15 The corresponding

exo-alkene had been prepared from bicyclo[2.2.l]hepta-2,6-

diene by Simmons and Smith using methylene iodide in the

presence of zinc/copper couple.16 Cyclopropene also reacts

with 6,6-dimethylfulvene to form only an endo Diels-Alder

adduct,17 and this cycloaddition offers a convenient synthetic

pathway into the endo-tricyclo[3.2.1.02'4]octyl ring system.

Subsequently, the reaction of 6,6-dimethyl-(or 6,6-diphenyl)-

fulvene with 1,2,3-triphenylcyclopropene was reported by

Martin8 to give a 1:1 adduct. However, careful H nmr

analysis indicated that the adduct had the exo structure.

Cyclopentadiene also forms endo-syn-3-methyltricyclo-

[3.2.1.02,4]oct-6-ene with 3-methylcyclopropene.' Semi-

larly, 1,2-diphenylcyclopropene,21 1,2,3-triphenylcyclo-

propene,21 1,2-diphenylcyclopropene-3-carboxylic acid,21

and 1,2-diphenylcyclopropene-3-carboxylic acid methyl ester21

all form endo 1:1 adducts with cyclopentadiene at room tem-

perature Curiously, 3,3-dimethylcyclopropene does not

react with cyclopentadiene even at 100 C,20 presumably due








to large steric interactions of the geminal methyl groups

with the cyclopentadiene molecule in the transition state.

It is evident that such interactions are sufficient to

inhibit adduction in either the exo or the endo mode. If,

however, forcing conditions are used, sterically inhibited

reactions can be carried out, as in the case of the reaction

of cyclopentadiene with 3-acetyl-3-methylcyclopropene ethyl-

eneketal (1) at 140 C for 12 hours.19 The adduct so ob-

tained was shown, by chemical conversion to a known compound,

to have an exo structure. Even more anomalous was the

behavior of the ketone, 3-acetyl-3-methylcyclopropene (2),

which at 1400 C apparently rearranges to l-methyl-3-acetyl-

cyclopropene (3) before adduction with cyclopentadiene to

give endo-anti-2-methyl-3-acetyl-tricyclo[3.2.1.02'4]oct-6-

ene, as shown below.







CH3 +








33



3 3 : COCE0









The use of dienes other than cyclopentadiene in Diels-

Alder reactions of cyclopropenes has produced some strikingly

different results from the standpoint of the stereochemistry

of [4 + 2] adducts. Indeed, the predominant stereochemistry

of adducts produced in reactions of alkyl- and aryl-cyclo-

propenes with furan is exo. Cyclopropene reacts with furan

to give a 1:1 mixture of exo- and endo-8-exatricyclo[2.2.1.02'4]-
22,23
oct-6-ene.2 When 1,3-diphenylisobenzofuran is the diene

component, exo products are obtained with cyclopropene, 1-

methylcyclopropene,24 1,2-diphenylcyclopropene,25 and 1,2,3-

triphenylcyclopropene.21 After 3 days in refluxing xylene,

tetraphenylcyclopropene and 1,3-diphenylisobenzofuran showed

no signs of reacting,21 but 3-methyl-l,2,3-triphenylcyclo-

propene under the same conditions gave after 3 days 3-methyl-

1,2,3,4,5-pentaphenyl-[6,7]-benzo-8-oxatricyclo[3.2.1.02'4]-
21,24
oct-6-ene2124 (albeit in only 8% yield). This behavior by

a tetra-substituted cyclopropene is in sharp contrast to the

findings using cyclopentadiene, which were discussed above.

Clearly then, the steric and electronic factors controlling

the stereochemistry of addition as well as the reactivity on

Diels-Alder reactions of cyclopropenes vary considerably

between cyclopentadiene and furan or 1,3-diphenylisobenzofuran.

It is instructive to examine the evidence used by the

various investigators to evoke either exo or endo stereo-

chemistry for [4 + 2] cycloadducts of alkyl- and aryl-cyclo-

propenes. In some cases stereochemical assignments are based

on comparisons to known compounds15,16,17,20 and in others 1H









nmr data are used to make the assignments.21'22,23,24,25

The adducts of cyclopentadiene with 1,2,3-triphenylcyclo-

propene and 1,2-diphenylcyclopropene-3-carboxylic acid

were ascribed endo configurations based on the chemical

shift of the lone cyclopropyl proton, which in either case

appears at higher field than expected due to shielding by

the C=C double bond. When both adducts were reduced to the

saturated compounds with diimide, the cyclopropyl proton

signal is shifted downfield by approximately 0.5 ppm, as

shown below.

















/ [N2H2]

2COH Co2H

T 7.72 2 T 7.27 H C



18
An analagous argument was used by Martin8 to settle

the question of stereochemistry in the 6,6-dimethylfulvene

adduct (4) of 1,2,3-triphenylcyclopropene. Comparison of

the chemical shift values of the cyclopropyl benzylic

proton in this adduct with the same proton in the exo-anti-








(5) and the endo-anti-(6)-2,3,4-triphenyltricyclo[3.2.1.02'4]

oct-6-enes pointed to the exo structure of the fulvene

adduct, as shown below.





53.27 763.75




62.55 H

4 5 6


22,23
Turning to the adducts of furan22'23 and 1,3-diphenyl-
24,25 1
isobenzofuran,225 1H nmr prarmeters have once again been

used to elucidate stereochemistry. The reaction of cyclo-

propene with furan produces a 1:1 mixture of the exo(7)-

and endo(8)- adducts. In the exo case, no significant

coupling is observed between the bridgehead protons Hb and

the cyclopropyl methine protons H However, in the endo
x
adduct, the II nmr spectrum indicates substantial H -H
b x
coupling. The cyclopropene adduct24 (9) and the 1,2-diphenyl-


Hb H Hb
H b H
Sx 5175
66.42 65.95 Hx 61.75
H I x x
v b H 61.0 v b H
64.55 x 64.77

bx- 0 Hz Jbx 0 Hz









cyclopropene adduct25 (10) of 1,3-diphenylisobenzofuran

were both assigned exo structures based on the observed

chemical shifts of their cyclopropyl protons syn to the

oxygen bridge in either case. This type of proton is

subject to steric deshielding by the lone electron pairs

on the oxygen. Shown below are the chemical shifts, multi-

plicities, and observed coupling constants for 9 and 10.


6 (mult) J(Hz)

1.84 J a 5.2
(d of t) ab
0.84 J = 3.7
ax
1.62 (d of d) Jbx= 6.74


6

H 2.94
a
Hb 1.80
h


(mult) J(Hz)

(d)
J ab 4.7
(d) ab


Thus, it would seem that by careful consideration of

II nmr data obtained for Diels-Alder adducts of alkyl- and

aryl-cyclopropenes, it is possible to make definitive exo

of endo structural assignments with a reasonable degree of

certainty.









The task of rationalizing why these cycloadditions

of furan and 1,3-diphenylisobenzofuran give exo products

in variance to the Alder rule5 is no less difficult than

ascertaining the correct stereochemistry of the adducts.

LaRochelle and Trost22 advanced such an explanation based

on the transition state structures for exo and endo

adduction. They envisaged an exo transition state as

being distinctly like a boat cyclohexane (as shown below),

and thus subject to destabilization by 1,3 "flagpole"

interactions, which could be substantial in those cases

where the diene is cyclopentadiene. When the -CH2- of

cyclopentadiene is replaced by -0- (furan or 1,3-diphenyl-

isobenzofuran), the 1,4 steric interactions in the exo tran-

sition state are evidently reduced enough to enable the

reaction to proceed to give exo products. However, it must








____ -- ----- ----- --------- H ,






be pointed out that although this transition state argument

seems to adequately explain the results of the Diels-Alder

reactions of alkyl- and aryl-cyclopropenes, it obviously

does not take into consideration electronic factors and

other steric interactions in the transition state which may









also be substantial enough to affect the exo/endo ratio

of products.


Halocyclopropenes as Dienophiles


Armed with the knowledge that alkyl- and aryl-cyclo-

propenes undergo Diels-Alder reactions with acyclic and

cyclic 1,3-dienes, several authors undertook investigations

directed towards the synthesis of and Diels-Alder reactions

of halogenated cyclopropenes. Since 1963, several thermally

stable halogenated cyclopropenes have been synthesized.

In that year, Tobey and West reported the dehydrohalogenation

of pentachlorocyclopropane in 18M aqueous KOH to give tetra-

chlorocyclopropene (11),2627 which these same authors sub-

sequently employed as the starting material for tetrabromo-

cyclopropene (12), 3-fluoro-l,2,3-trichlorocyclopropene (13),

1,2-dichloro-3,3-difluorocyclopropene (14), and 1,2-dibromo-

3,3-difluorocyclopropene (15).28 Reduction of 11 with tri-

n-butyltin hydride as reported by Breslow et al. 29affords

a mixture of 3-chlorocyclopropene (59%), 3,3-dichlorocyclo-

propene (14%), and 1,3-dichlorocyclopropene (27%). In 1969,

Cl H H H

II C + I



11


Sargeant and Krespan reported the successful synthesis of

perfluorocyclopropene (16), as well as the duplication of









the synthesis previously reported of 1,2-bis(trifluoro-

methyl)-3,3-difluorocyclopropene (17).31,32 Other reported

gem-difluorocyclopropenes include some 1-(perfluoroalkyl)-

3,3-difluorocyclopropenes33 and some steroid derivatives

incorporating a gem-difluorocyclopropene moiety.34

Since many of the cyclopropenes mentioned above are

thermally stable and relatively high boiling, several authors

have taken advantage of these properties to prepare [4 + 2]

cycloadducts with a variety of cyclic and acyclic dienes.

Since the structural assignments of these adducts rests on

conclusions drawn from spectral data, these data will be

closely examined. Also, due to the subtle differences ob-

served in the spectra for pairs of stereoisomers, such

differences will be discussed in terms of their relevance

to making structural assignments.

The most widely reported perhalocyclopropene to be

used as a dienophile is tetrachlorocyclopropene (11), which

forms 1:1 adducts with furan,3536 13,14-dioxatricyclo-

[8.2.1.14',7 tetradec-4,6,10,12-tetraene,37, 1,3-diphenyliso-

benzofuran,24,38 cyclopentadiene,35 and the acyclic dienes

1,3-butadiene,35 and trans,trans-1,4-diphenyl-l,3-butadiene.3

The observed ring opened product of 11 with furan was envis-

aged by Law and Tobey to arise through an initially formed

endo tricyclic adduct, which at the reaction temperature

(800 C) undergoes facile ring opening to 2,3,4,4-tetrachloro-

8-oxabicyclo[3.2.1]-octa-2,6-diene. Completely analagous

behavior was observed for tetrabromocyclopropene (12), as









shown below. These authors based their conclusion that the



X x x

Scc x
X 80C \X

X X
11 x = Cl

12 X = Br


initially formed [4 + 2] adduct was endo on transition state

calculations carried out by IIerndon and Hall40 on the cyclo-

pentadiene dimerization, and transition state steric argu-

ments for the system shown above. An interesting alternative

mechanism for the above reaction was considered by Magid and

Wilson,36 which involved ionization of a labile methylene

Cl in 11 to form the trichlorocyclopropenium cation, which

subsequently formed an ionic cycloadduct with furan, followed

by rapid ring opening and capture by Cl to yield the observed

product. However, their kinetic data obtained from the

reaction using cyclopentadiene as the diene instead of furan,

as well as stereochemical studies,36 precluded adoption of

this ionic mechanism in that the data were more consistent

with the direct cycloaddition mechanism.

A contrasting opinion of the stereochemical mode of

tetrachlorocyclopropene (11) cycloadditions was advanced in

1971 by Battiste et al., who suggested that the initial

reaction of 11 with the [2,2] (2,5)-furanophane shown below

occurs to give the exo adduct, which undergoes further









reactions. These authors cited the analagous reactions of






11 + Cl '1


i+
Cl



furan and 1,3-diphenylisobenzofuran discussed above22'29 as

the basis for their supposition. Since it is impossible to

obtain absolutely reliable stereochemical information from

spectroscopy alone for adducts of tetrachlorocyclopropene

(11), other means must be sought for accurate structure
38
determinations. In this vein, Bordner and Howard, in

collaboration with Magid and Wilson, have recently con-

ducted a single crystal X-ray analysis of the adduct of 11

with 1,3-diphenylisobenzofuran, which revealed that the

adduct is unquestionably exo, thus lending support to the

contention that perhalocyclopropene Diels-Alder reactions

may in fact proceed in the exo, or "anti-Alder" manner.

When one or both of the geminal positions of a perhalo-

cyclopropene are substituted with fluorine, the mono- or

gem-di-fluorocyclopropenes, when reacted with a diene, form

the corresponding fluorinated cyclopropanes, which in many

cases are stable to ring opening at the reaction temperature

due to the inherent strength of the C-F bond. The fluorinated

cyclopropenes that have been studied as dienophiles have been








synthesized principally by Tobey et al., 2835 and
30,31
Sargeant. 1 Tetrachlorocyclopropene (11), when treated

with SbF3, forms a separable mixture of 1,2,3-trichloro-

3-fluorocyclopropene (13) and 1,2-dichloro-3,3-difluoro-

cyclopropene (14). Tetrabromocyclopropene (12), when

subjected to treatment with SbF3 at somewhat higher tem-

peratures forms a single product, 1,2-dibromo-3,3-difluoro-

cyclopropene (15). Diels-Alder adducts with furan for all


SCl

1H
ci ->' Cl/ + v ci
Cl F H
13 c (126.7) v b b Cl

(138.4)
Hb(5.30)
H (6.83)

18

C1 Ib
SF H C1 ib(5.26)

F H (6.87)
Cl H H
V b (103.7)
14 F
4(136.7)

19





Br Hb
F H Br (5.29)
SV -3 r H (6.81)
B H b F (92.0)
15 F
15 (136.5)









three of these fluorocyclopropenes were first prepared in

1968 by Law and Tobey35 and were assigned the structures

shown above. The 1H nmr chemical shifts are in 6 relative
19
to TMS, and the 1F nmr chemical shifts are in 6 upfield

from CFC13. All shift values shown are as reported by Law

and Tobey, and the assignments are their own.

Close inspection of the nmr data for the tricyclic

compounds 18, 19, and 20 reveals some interesting features.

First, a fluorine cis to either Br or Cl has a signal at

lower field than a trans fluorine. Note that in the mono-
19
fluorinated compound (18), the single 1F resonance may be

assigned with reasonable certainty to a fluorine trans to

the two bridgehead Cl atoms. Also, the 6 values indicate

more efficient deshielding by a cis Br than a cis Cl, as

expected. Second, in both of the gem-difluoro compounds,

(19) and (20), only one fluorine, the fluorine trans to

either Br or Cl and at highest field, is coupled to Hb (J

2 Hz). The single fluorine resonance of the monofluoro

compound (18) also appears as a triplet (J = 2.5 Hz), thus

supporting the other assignments. Tobey and Law in 1968,

with Magid and Wilson concurring in 1971, therefore assigned

the endo structures to 18, 19, and 20 as shown above. How-

ever, if all three structures are considered to be exo, the

S Hb F(136.5)
(H90 H (5.829)
(92.0) H (6.81)
is .*+-- / / ~ivV


"20a"









nmr data can be made to "fit" equally well, as shown above

taking 20 as an example. In accordance with the criteria

established above, in the now exo 20a, the lowest field

fluorine is cis to the two Br atoms, and the higher field

fluorine is coupled to Hb and appears as a double of

triplets (JFF = 144 Hz, JFHb = 2 IHz). Tobey and Law argued

that in 20, the high field fluorine is shielded by the C=C

double bond since this adduct was thought to be endo. This

argument is not justified, since the same shielding argu-

ments that are well established for 1H nmr cannot be applied
19 41
to F nmr. This is particularly so in the compounds in

question, due to the lack of data for suitable model com-

pounds. Two other furan adducts of gem-difluorocyclopro-

penes have been reported by Sargeant.31 Tetrafluorocyclo-

propene (16) and 1,2-bis(trifluoromethyl)3,3-difluorocyclo-

propene (17) form 1:1 furan adducts, 21 and 22, respectively,

at room temperature, both of which are shown in Table I with

the structural and nmr spectral assignments as made by Sargeant.


Table I

1H and 19F nmr Data for 21 and 22

6ppm mult. splitting, Hz

6H
a
F 6.32 M Wb- 4

Fc 4.60 2 X M 3.4, Wb ~ 8

b F 6F
b a
129.9 2 0.3

139.3 3 X 3 23.3,3.2

227.8 2 23.4


assign. J,Hz


F F =
aFb
175

F F=
b c
0.0

23.4

H F =3.2
a,b a









Table I Continued


6ppm mult. splitting, Hz assign. J,Hz

5H

H d a CF 6.62 1 W 1/2 ~ 3.8 c,d CF
H CF3 1/2 3 a

/H CF 5.17 1 W 1/2 3.8 a,b 16
H b
c F a 5F CF3 F


22 59.7 2 X 2 16, 2.2 CF3 2.2
22
116.7 7 15.9 F F F =
a ab
137.0 7 X 3 2.2, 1.2 Fb 166

H Fb
a,b b
1.2



A detailed comparison of the nmr spectra for 21 and

22 with data accrued earlier for similar compounds does

not, in fact, lend support to the structures shown above,

as discrepancies can be noted. First, compared to the

previously discussed compounds, Fa and Fb in Sargeant's

tetrafluorocyclopropene adduct (21) would seem to have

their assignments reversed, were it not for the large

(23.3 Hz) coupling between F and F which allows un-
c a
ambiguous assignment of F to the signal at 6139.3. Sec-
a
ondly, if 21 were actually endo, one would expect to see

substantial coupling from Ha,b to Fc, which should be as

large, if not larger, than the H H coupling observed

for bridgehead proton (Ha,b) exo H2, H4 interactions.20
21,42,43
3 No such coupling is reported for 21 and no W /2

data were cited for the F doublet. The anomalies
c









1 19
within the H and 1F nmr data require that the alternate

exo structure 21a be considered. To this end, 21a, the

revised exo structure, accompanied by the reassignments
1 19
for the H and 19F nmr spectra, are illustrated in Table

II. Even though this structure eliminates the problem of


Table II
1 19
II and 1F nmr Data for 21a



6ppm mult. splitting, Hz assign. J,Hz

H aJb 61 FaFb

d Fa 6.32 M Wb ~ 4 c,d 175
/ ~ F
H b \ c 4.60 2 X M 3.4, Wb ~ 8 a,b FF =

6F 0.0
21a
129.9 2 0.3 Fb FaF =
b a c
139.3 3 X 3 23.3, 3.2 F 23.4

227.8 2 23.4 F F H a,b(?)=
c a a,b
3.2


no observed J F (since bridgehead-H/endo-H coupling
a,b c 42
is usually negligible), the chemical shift values as

assigned here do not agree with the previously observed35

appearance of the geminal fluorine cis to C21C4 cyclopropyl

halogens at lower field than the trans geminal fluorine.

Thus, it would seem that in the absence of other data to

resolve the paradox, such as heteronuclear decoupling re-

sults, the assertion by Sargeant that "the stereochemistry

[of 21] cannot be assigned with certainty" must remain un-

changed.









Re-evaluation of the structure of the 1,2-bis(tri-

fluoromethyl)-3,3-difluorocyclopropene adduct 22 in the

same fashion (that is, as the exo adduct 22a), may prove

more productive than in the case of 21. Once again,

fitting the observed H and 1F nmr data to 22a, one

obtains the results shown in Table III. Of interest here

Table III
1 19
H and 1F nmr Data for 22a


6ppm mult. splitting, Hz assign. J,Hz

a b 6H CF3F =
3a
d F a 6.62 1 W1/2 ~ 3.8 c,d 16
3
H b CF3 5.17 1 W1/2 3.8 a,b CF3Fb

6F 2.2
22a
59.7 2 X 2 16, 2.2 CF3 FF =
3 ab
116.7 7 15.9 F 166
a
137.0 7 X 3 2.2, 1.2 Fb H,bFb

1.2



is the value for Fb, which in this case is rather close to

the value for Fb in Tobey and Law's furan adduct of 15. The

spectral data for that adduct (20a) were likewise argued to

be consistent with exo stereochemistry (see p 17). In ad-

dition, the assignment of Fa to the lower field signal is in

line with the previously discussed trend. In fairness, how-

ever, either the exo structure 22a or the endo structure 22

can be fitted to the data, as Sargeant readily acknowledged.31









Thus, if the structure of one of these furan Diels-Alder

adducts could be established concretely, the development

of diagnostic techniques applicable to other compounds

of this type might be in the offing.

The problem of correctly assigning stereochemistry

in halocyclopropene adducts is further confounded by the

existence of a body of data for cyclopentadiene adducts

of other halocyclopropenes. One such study by Magid and

Wilson36 dealt with cyclopentadiene adducts formed by

reaction of excess cyclopentadiene with a mixture of 3-

chlorocyclopropene, 3,3-dichlorocyclopropene, and 1,3-

dichlorocyclopropene.2936 Curiously, these authors did

not report formation of an adduct from the 3,3-dichloro-

cyclopropene. However, the remaining cyclopropenes afford

1:1 adducts 23 and 24, both of which appear to be exclusively

endo, as shown below with the appropriate 11 nmr data. Other

evidence for structures 23 and 24 was obtained from the



61.7H H61.7 61.81H H61.81



> H HH H62.20
HH H H
H 65.85 H C1 66.01
62.48 62.95
(J = 1.5Hz) (J = 2.5Hz)



23 24


reaction of norbornadiene with chlorocarbenoid, which yielded









the monochloro endo-anti compound 23 as well as the exo-

anti isomer 25 shown below with its 1H nmr data. (That



60.8 61.1
H H H63.68
CH C12 H Cl (J = 1.5Hz)
S23 +
H
S CH3Li -

66.45 H
25

26% 74%



carbene additions to bicyclic systems such as norbornadiene

proceed to give preferentially exo addition products has
43,44
been well documented,444 and will be discussed later.)

Finally, reduction of 23 by sodium in tert-butyl alcohol

produced only the known endo-tricyclo[3.2.1.02'4]oct-6-ene.

Other than the ring opened adducts of tetrabromocyclo-

propene (12) and tetrachlorocyclopropene (11) prepared by

Law and Tobey,35 only two other halogenated cyclopropenes

have been treated with cyclopentadiene, namely 1,2-bis(tri-

fluoromethyl)-3,3-difluorocyclopropene (17) and tetra-

fluorocyclopropene (16), as reported by Sargeant.31 Cyclo-

pentadiene when reacted at room temperature for 24 hours

with 16 gave only 2,3,3,4-tetrafluorotricyclo[3.2.1.02'4]-

oct-6-ene (26), but the bis(trifluoromethyl) compound 17

gave two products, 27 and 28, in 90% yield in a 69:31 ratio.

Once again, all three of these compounds with the nmr data










as reported and assigned by Sargeant are shown in Table IV.


Table IV
1H and 19F nmr Data for 26, 27, and 28
H and F nmr Data for 26, 27, and 28


6ppm

6H

6.71

3.23

1.75

1.19


mult. splitting, Hz assign.


3

7

M

M
(3X3X2)


6F

128.1 7

134.8 M
(3X3X3)

221.0 M
(2X2X3
X2)


611

6.72

3.57

2.01

1.15

6F

59.9

113.7

129.9


2 X 2

7

2 X 7


1.4

1.8, Wb -14

W/2 ~ 4.5

6.0, 2.1, 2.1




0.4, W1/2 6

24.3, 4.3, 1.8


24.4, 6.3, 2.3, F
and 1.4


W1/2 -5.5

W1/2 ~ 6.5

W1/2 ~ 4

W1/2 8



19.0, 2.6

19.0

2.8, 2.6


H He
, _, e


J,Hz

H H =10.5
e f
H F =6.3
ec

F Fb=177
ab
F H =1.8
a c,d
FF =24.3
ac


F H =4.3
a a,b

F H -2.3
c a,b
FbFC=1.4
FE 14


H H
fC, e


HeH= 8.6
ef

F CF 3=19.0
a 3

F CF =2.6

FFb=178

H Fb=2.8









Table IV Continued







6ppm mult. splitting, Hz assign. J,Hz
11f He 6H H H =8.4
e Fb
H aA 6.27 2 X 3 3.2, 2.0 c,d CF F =19.0
3a
CF3 3.57 1 W2 ~ 6.5 a,b CF3F =2.6
c b CF3 2.36 1 W1/2 ~ 5 e FaFb=177

1.84 1 W/2 ~ 7 f H Fa=8.5
28 1/2 a
6F

61.7 2 X 2 19.0, 2.6 CF3

109.4 7 X 2 19.0, 8.5 F
a
136.0 7 2.6 Fb

The assignments of stereochemistry in 27 and 28 as

well as some of the nmr chemical shift assignments are

somewhat suspect, and it becomes necessary at this point

to indicate several anomalies in Sargeant's proposed

structures. First, on chemical grounds, one would expect

both tetrafluorocyclopropene (16) as well as 1,2-bis-

(trifluoromethyl)-3,3-difluorocyclopropene (17), when

reacted with cyclopentadiene, to imitate the propensity

of other cyclopropenes towards preferential, if not ex-

clusive, endo addition.15'18'19'20 However, Sargeant pro-

posed the exo compound 28 as the major reaction product.

Also, cyclopentadiene adducts of this general type are

believed as a rule to be more thermodynamically stable when

in the exo form,1,45 in spite of any steric interaction









between a syn bridge hydrogen and a cyclopropyl methylene

substituent. Thus, the isomerization of 28 to 27 envis-

aged by Sargeant would not be anticipated based on the

relative thermodynamic stabilities of the two isomers.

In addition, the assertion by Sargeant that exo 28 iso-

merizes to endo 27, which further rearranges to the

tetracyclic system 29 as shown below seems curious in that

conversions of the type that give tetracyclic products such

as 29 are believed to take place from the exo stereoisomer.




F 2 R.T. CF3 2001C 3

CF CF
CF CF3 CF2
CF3 F CF3
2
28 27 29

Further examination of the nmr data for 27 and 28 also

suggests that their structural assignments are reversed.

Recent analysis6 of the H nmr spectrum of endo-1,5,6,7-

tetrachlorotricyclo[3.2.1.02'4]oct-6-ene (30) has shown



H H1
THl
Cl 3
H3


H H411
30

that substantial long range coupling amount to 2.5 Hz exists

between the anti bridge proton H2 and the outside cyclopropyl









1 19
methylene proton H Since H F long range couplings

are usuallylarger in magnitude than the corresponding
1 1 47 1 19
H H couplings, the H and F spectra of the adduct

thought by Sargeant to be endo (27) should contain evidence
19 1
of long range 1F H coupling from anti proton Hf to the

outside fluorine F According to the assignments made
a
by Sargeant, though, F appears as a clean septet coupled
a
only to the CF3 groups (J = 19.0 Hz). There is also an

unassigned coupling to Fb of 2.8 Hz. However, in 30, Ji,4

is only 0.30 Hz, so that the coupling FbHe could possibly

be 2.8 Hz, but no data pertinent to this question are

available at the present time.

Turning to 28, claimed to be exo by Sargeant, there

is a large coupling to Fa (cis to the CF3 groups), amounting

to 8.5 Hz, which Sargeant left unassigned. Noteworthy also

is that of the two bridge protons H and Hf, only Hf, at

61.84, has a W1/2 (-7 Hz) sufficient to possibly accommodate

an 8.5 Hz long range fluorine coupling. In view of the

contradictions manifested by 27 and 28 in their chemical

behavior as well as the anomalies present in their nmr

spectra, it is instructive to reverse their stereochemical

assignments. That is, assuming 27 to be exo (27a) and 28

to be endo (28a), it is possible to analyze and assign the

observed nmr data more satisfactorily- The revised exo/

endo assignments are presented in Table V with the appropriate

nmr data. Examination of the revised assignments in Table V

leads to a more satisfying fit with empirically determined










Table V
1H and 19F nmr Data for 27a and 28a
H and F nmr Data for 27a and 28a


Sppm

6H

6.72
Fb
F 3.57

YF3 2.01

CF3 1.15

6F

59.9

113.7

129.9


6H

6.27

3.57

2.36

184

6F

61.7

109.4

136.0


mult. splitting, Hz


2 X 2

7

2 X 7


2 X 3

1

1

1


W1/2 ~ 5.5

W1/2 6.5

W1/2~ 4

W1/2 8



19.0, 2.6

19.0

2.8, 2.6


3.0

1/2 ~ 6.5

W1/2~ 5

W1/2 7



19.0, 2.6

19.0, 8.5

2.6


assign. J,Hz

H H =8.6
et
c,d F CF 3=19.0
a 3
a,b FbCF3=2.6

f FaFb=178
ab
e FbH?=2.8



CF3

F
a
F


H II=8.4
ef
F CF =19.0
a 3
FCF3=2.6

FFb=177

FaH =8.5
af









trends in the nmr spectra of tricyclic compounds of this

type. First, the appearance of He at higher field than

Hf is consistent with shielding of He by the exo cyclo-

propane ring. Note that 6He in endo 28a is greater than

6He in 27a, supporting this mode of shielding for the

exo compound. Second, a tentative assignment of JF H
19 1 b ab
in 27a can be made, since 4-bond 1F H coupling of the

order of 2.8 Hz is not unusual.3547 Lastly, the most

telling argument for the structural assignments above is

the assignment of the large (8.5 Hz) long range F H

coupling of F to Hf, which in 28a should be much larger
19 1
than any long range F H coupling in 27a.

If 27a and 28a are indeed the correct structures for

Sargeant's adducts, the isomerization data he reported

adhere more closely to the known thermal behavior ob-
1 48
served in other exo and endo tricyclic compounds.'48 In

addition to the fact that the preferred endo adduct 28a

now becomes the major reaction product, the isomerization

at room temperature of the less stable 28a to the more

stable exo isomer (27a) now parallels existing data.1,48

Also, the quadricyclic product 29 as depicted below is now

seen as arising from 27a upon heating at 2000 C instead of

from 28a, again in conjuction with previous data.18,23,48

To conclude, then, that 27a and 28a are the correct

structures for the Diels-Alder adducts synthesized by

Sargeant seems quite reasonable, in terms of both their

chemical behavior as well as the nmr spectral data reported.











R.T.
CF



CF3 CF3 /CF3

CF
3 F2
17 27a 28a 2

(31%) (69%)


2000C






CF3
29


Recent work by Jefford et al. 49 involving difluorocarbene

addition reactions (which will be discussed later) has,

in fact, given strong indications that our reassessments

of the structures of 27 and 28 and their spectra are most

probably correct.

Unfortunately, there are several inconsistencies in

the data reported31 for the cyclopentadiene adduct 26 of

perfluorocyclopropene (16), which make the unambiguous

assignment of stereochemistry impossible. For example, F
a
appears at higher field than Fb, in contrast to previously

reported35 data for other gem-difluorocyclopropene adducts.

Also, a coupling of 2.3 Hz is assigned to JF H whereas
c a,b
this type of coupling should probably be on the order of

3.5 4.0 Hz.20, 21, 42, 43
3.5 4.0 Itz.









Objectives of This Work


Given the number of Diels-Alder adducts of perhalo-

cyclopropenes that have been prepared and the paucity of

definitive structural information about these compounds,

there was an obvious need for reinvestigation of many of

the reactions in question with an eye towards establishing

reliable criteria for making structural assignments in

these systems, as well as correcting any erroneous structural

assignments. To develop the synthetic potential50 of cyclo-

propene Diels-Alder reactions to the utmost, those who

utilize these cycloadditions must have at their disposal

the means by which exo/endo assignments can be made with

certainty. Several methods by which such assignments may

be made lend themselves to the work in question. The most

likely methods to be used are the spectroscopic techniques,
19 1
especially 1F and H nmr. But for these to acquire the

reliability sought, a great many more data must be compiled

for a variety of structural types. However, the method that

is possibly the most unassailable, and a technique which is

coming more and more into prominence in organic structural

studies, is single crystal X-ray analysis. This method has

the advantage of requiring a minimal amount of material, and

since the output is usually in the form of computer drawn

structures, relatively subtle differences in bonding or

stereochemistry, which might be undetectable otherwise, can

be clearly ascertained.

Our objective was to establish the structure of one of









the previously reported fluorinated cyclopropene adducts

by X-ray crystallography, and then using the 1H and 19F

nmr parameters for this "known" system, to develop nmr

spectral criteria for making structural assignments in

related systems. Included in this endeavor was the syn-

thesis not only of the cyclopropenes and the Diels-Alder

adducts thereof, but chemical conversions of most of these

adducts to new compounds so that the methodology used might

be expanded to include more structural types. Specifically,

these transformations consisted of reducing the C=C double

bonds in some adducts and/or treatment of these vic-dihalo-

gem-difluorocyclopropanes with tri-n-butyltin hydride to

obtain the corresponding gem-difluorocyclopropanes. The

characterization of these compounds was expedited by the

distinctive IH and 19F nmr spectra of the general structure

shown below.


X H
F (n-Bu) 3SnH F

S F \ F
X H

X = Cl, Br



It is interesting to note that the synthetic step

depicted above is equivalent with respect to the overall

structures involved to (i) performing the original Diels-

Alder reaction using 3,3-difluorocyclopropene as the dieno-

phile, or (ii) addition of the difluorocarbene (:CF2) moiety




33



to a cyclic or bicyclic olefin. What may not be as

analogous is the stereochemistry of the products so

obtained. For example, while some of the [4 + 2] cyclo-

additions might yield endo products, their exo analogs

should be obtainable via the difluorocarbene sequence.

The discussion of the details of our synthetic investiga-

tions of 3,3-difluorocyclopropene as well as discussion of

difluorocarbene additions will be deferred until the ap-

propriate time in Chapter II, in order to avoid redundancy.















CHAPTER II


RESULTS AND DISCUSSION


Stereochemical Studies of Perhalocyclopropene
[4 + 2] Cycloadducts


As discussed earlier, in light of the imprecise nature

of assigning stereochemistry to Diels-Alder adducts of

perhalocyclopropenes, it was our belief that a means

should be found to unambiguously assign an exo or endo

structure to one such compound, and then apply the spectral

parameters observed for that compound to other similar adducts

of unproven structure. We selected as our model system 2,4-

dibromo-3,3-difluoro-8-oxatricyclo[3.2.1.02'4]oct-6-ene (20),

first prepared by Law and Tobey in 196835 from 1,2-dibromo-

3,3-difluorocyclopropene (15) and furan, and assigned the

endo structure shown. This compound is one of the "stable"


Br
F CCI
4 Br
F 80C / Br
Br

F F
15 20



adducts of this general type that have been prepared, meaning

that 20 appears to be thermally stable to ring opening









reactions at 1000 C, the pot temperature used by Law and

Tobey in their distillation of 20. As elaborated earlier,

nmr spectroscopy did not provide a suitable proof for the

stereochemistry of 20. To this end, it was deemed es-

sential that a single crystal X-ray analysis should be

carried out on the same material that was reported by

Law and Tobey.

Synthesis of 20 naturally required 15 as a precursor,

and the reaction sequence developed by Tobey and West26,27,28

was repeated, as shown in Scheme I (for specifics concerning

yields, etc., see Experimental). The Diels-Alder reaction

Scheme I


C1
Cl2C=CHC1 + Na O2CCCI3 Cl
C Cglyme CI
Cl c ClH C 1 Cl



11
Br
11r Br

Br
Br 12
Br
SbF3
12 )
-- A

Br 15




was carried out as described by Law and Tobey. Instead of

using only a short path distillation, however, our crude

reaction mixture was passed through florex with pentane,









the solvent was removed, and the residue was sublimed to

give a material which had all spectral properties identical

to the literature report.35 Oddly, the melting point of the

sublimed adduct was 360 lower than the literature value,

so that the state of purity of the material from our sub-

limation required closer examination. Analysis by gas

19
chromatography as well as reexamination of the 1F nmr

spectrum of this material indicated that only one adduct

was present, and that it was indeed identical to the com-

pound reported as 20.

Having established the authenticity of our furan adduct,

the next step in the structural determination was the re-

action of 20 (20a) with phenyl azide (31) to form a 1:1

adduct, 32. There were two major reasons for preparing 32.






SBr
20 + N3 ->
F2

r
H
32

First, 20 (20a) proved to be far too volatile at room tem-

perature to permit analysis by X-ray diffraction, and second,

although 20 (20a) was a solid, 32 formed crystals that were

more amenable to the shaping and mounting procedures required

for single crystal X-ray studies (see Experimental). The

results of the X-ray structural determination are shown in





37






o












'u
UU
U










U U






o C





N


r-A



C)
u Q




UN








C )

U 0




ciI-i) ci








ci









Figure 1, which is a stereoview of the complete structure

of 32. As anticipated,51the phenyl azide moiety added

to 20 (20a) in a 1,3-dipolar fashion, resulting in the

formation of the exo 5-membered ring. Of paramount

importance, however, as Figure 1 unmistakably shows, the

gem-difluorocyclopropane ring also has the exo stereo-

chemistry. One consequence of this finding is that the

structure of the original Diels-Alder adduct (from which

32 was synthesized) had to be 20a, the exo structure dis-

cussed earlier, and not 20, the endo isomer originally

proposed by Law and Tobey. The immediate impact of this

single result was that the stereochemistries assigned to
35
the other furan adducts prepared by Law and Tobey as well

as those prepared by Sargeant,31 required reevaluation.

Using 20a, now known to be exo, as starting material,

three other compounds were synthesized from it that retained

the gem-difluorocyclopropane ring. These chemical trans-

formations are shown in Scheme II. It should be noted that

Scheme II

Fb b H2 b
F [N2H2 (n-Bu) SnH F
a a H a
\r or \Br A 1

Br H2Pd/C Br (t-BuO)2 2 H1
20a OoC 33 34




SFHa Fb
2 F
(n-Bu) 3SnH Y 3 N 3
aH a
(t-BuO)2, A n
21 1


H 36









of the reactions used in Scheme II, none are currently

suspected of causing exo to endo isomerizations, either

by a retro-Diels-Alder type mechanism, or by inversions

at individual carbon centers. In support of our contention

that all of the compounds in Scheme II have the exo

structures shown, is the 19F chemical shift of Fb, which

for the brominated compounds 20a and 33 has values of

136.5 ppm and 135.5 ppm, respectively (also, as further

proof, in the phenyl azide adduct 32, 6Fb is 134.2 ppm),

indicating that Fb in each case resides in approximately

the same environment. When the bridgehead Br atoms are

reduced to hydrogen atoms, as in 34, 35, and 36, Fb now

appears at 145.9 ppm, 143.4 ppm, and 144.9 ppm, respectively,

again indicative of equivalent environments in these com-

pounds, as well (for complete H and 19F nmr data, see

Table IX, p 87 ). Of course, correct assignments of Fa
19
and Fb are crucial if the observed trends in 1F nmr

chemical shift values are to be of any use. In 34, 35, and

36 (and hence in their precursors in Scheme II) this task

is made trivial by observation in the 19F spectra of the

large (12-13 Hz) triplet coupling of F to the cyclopropyl
a
protons. This cis-vicinal 1F H coupling is much larger
19 1
than the trans-vicinal 1F H coupling, which is 1.5 2.5

Hz. Therefore, in principle, if a gem-difluoro-1,2-dihalo-

cyclopropane can be successfully reduced in the manner shown
19
above, F nmr assignments should be rather straightforward.

In conjunction with the above technique, correct assign-

ment of stereochemistry in analagous compounds can now be









made by conversion of one of the compounds of known

stereochemistry to a compound which can also be derived

from an adduct of unknown structure. In lieu of this direct

method, since such conversions are not always possible, we

have made use of three other spectroscopic techniques for

determination of stereochemistry. The first of these

techniques involves measurements in 1H nmr spectra of line

widths at half height (W1/2), which gives a measure of the

maximum value that can be attributed to all couplings to

the particular nucleus under scrutiny. For example, in the
1
H nmr spectrum of 35, W1/2 for the cyclopropyl protons (H1)

is 0.75 Hz, indicating that JHH2 must be no greater than

this ceiling value. If 35 were endo, JH H2, and hence W1/2

for H1 would be expected to be much larger, as discussed
41,42
previously.4, Measurements of W1/2 will henceforth be

quoted when they are relevant to structural assignments.

Secondly, and as a further refinement of the W1/2 technique,

we employed heteronuclear decoupling to provide another means

of estimating coupling constants such as JHH 2. In a typical
19
experiment, each F nucleus was irradiated in turn and the

resulting 1H nmr spectrum was recorded. Also, due to the

A6 between 1H and 19F nuclei, both Fa and Fb could be simul-

taneously irradiated, giving a fully decoupled 1H nmr spectrum.

This method, therefore, provided a way of obtaining W1/2 data
19
from 19F decoupled spectra, which, when considered with the

undecoupled spectra, usually allowed for more certain exo/endo

assignments. Heteronuclear decoupling proved to be quite









useful for furan adduct assignments as well as for adducts

of some cyclopentadienes, which will be discussed later.

Finally, in those cases where an oxygen atom formed a

bridge in an adduct (of furan and related dienes), we had

hoped that the use of Eu(FOD)3 as a shift reagent might give

rise to a correlation between stereochemistry and the observed

rate of shift for the 1H resonances. The results we obtained

using 34 as a reference compound will be discussed at the

appropriate time, and although they were not as quantitative

as we had hoped, some interesting trends were observed from

which tentative inferences regarding the nature of Eu(FOD)3

complexation can be drawn.

Since 20a, as prepared by Tobey and Law,35 had the exo

structure as shown by X-ray analysis, the prospect of de-

tecting additional incorrect assignments became much more

likely. These suspicions were well founded, since the furan

adduct (19) of 1,2-dichloro-3,3-difluorocyclopropene (14),

considered to be the endo isomer by Tobey and Law, also

proved to have exo stereochemistry. Our proof of structure

consisted of duplicating the original synthesis of "19",

followed by saturation of the double bond to give 37 and

reduction of the methine Cl atoms, as shown in Scheme III.

The resulting saturated, dechlorinated material had an infra-

red spectrum identical to the infrared spectrum previously

recorded for 34, prepared from authentic exo 20a. In

retrospect, since the chemical shifts of Fb in 20a, 19a,
and the lone 19F in 8 (see Table I) fall within 2.0 pm of
and the lone F in 18 (see Table I) fall within 2.0 ppm of











Scheme III

F F F
F
F Na, THF F

S C 2, Pd/l t-BuOH
Cl 2 1 H
19a 37 34



20a


each other, the preliminary conclusion that all three of

these fluorocyclopropene adducts are exo has now been firmly

established for 20a and 19a, and a strong case can now be

made for exo stereochemistry of the monofluorocompound 18

(as 18a) as well. Noteworthy also, is the similarity of


H2 Fb (136.5) 112 b (136.7) H2 Fb (138.4)

F F Cl

H2 B2 2
Br 2 1

H2= J bH2=2.5 J H2=2.5
FbH2 FbH2 FI2

20a 19a 18a


JFH in all three compounds, which also points up the
b 2
resemblance in the structural environments for Fb in 18a,

19a, and 20a.

Bearing in mind the values for 6Fb cited above, the

previous discussion of the furan adducts 21 and 22, reported

by Sargeant31 to be endo, becomes more germane. If these









compounds are now taken to be exo, as mentioned previously,

the correlation between Fb, JFbH2, and exo stereochemistry

can be extended to 22a. The case of 21a has not yet been


H2 Fb (139.3) H Fb (137.0)


/ F a 2/ a
F c =3.22 ? 3CF = 1.2
c FE 3 HH
2 = ? 2 F b

bH2
J?
FH
21a c 2 22a



resolved, since Sargeant quoted no values for JFb2 or JFH2
b 2 Fc2
and there is still his reported JF = 3.2 Hz to be con-
a2
sidered in terms of making a satisfactory structural assign-

ment. Thus, no definite choice between endo 21 and exo 21a

can be made at this point.

Thus, having made the necessary corrections to the

structures erroneously designated as endo [4 + 2] adducts

of furan and some fluorinated cyclopropenes, attention was

turned to the synthesis of new perhalocyclopropene-furan

adducts, and then using the criteria discussed in relation

to 20a, to extend the number of unambiguous structural assign-

ments in this system. For several reasons, 1,2-bromo-3,3-

difluorocyclopropene (15) was the dienophile of choice, even

though its preparation involved four steps (see Scheme I) with

an average overall yield of about 3%. First, 15 was used in

the initial work in the X-ray analysis, and to change the

nature of the dienophile in use would have added another









variable to a mechanistic scheme already laced with un-

certainties. Second, from a more practical standpoint,

of the gem-difluorocyclopropenes previously discussed, 15

had the advantages of being thermally stable, non-volatile,

and most important, of possessing moderate relative re-

activity towards dienes.35 A choice of some other gem-

difluorocyclopropene would have meant compromising some or

all of the advantages of 15.

The first diene we chose to react with 15 was 1,3-

diphenylisobenzofuran, which is also thermally stable yet

fairly reactive towards dienophiles, due to the incipient

aromaticity of the benzo- moiety in the transition state

for adduction. When this reaction was carried out at 800 C

for 12 hours, the product consisted of 89.9% exo-2,4-dibromo-

3,3-difluoro-l,5-diphenyl-[6,7]benzo-8-oxatricyclo[3.2.1.02'4]-

oct-6-ene (38a) contaminated with 10.1% of the endo isomer

38. These assignments can be advanced on the basis of the

X-ray study done by Bordner and Howard38 which proved that

tetrachlorocyclopropene (11) also gives an exo adduct with

1,3-diphenylisobenzofuran. Also, on chemical grounds, the

product predicted to be the most stable isomer would be exo

(38a), and thus at 800 C should also be the major product.

The evidence to support the endo structure 38 consists of
1 19
the lack of signals in the H and F nmr spectra which could

correspond to another type of structural isomer. That 38 is

a structural isomer of 38a was borne out by the fact that the

mixture gave a correct elemental analysis for the formula of









38a/38. Also, the 19F nmr spectrum of 38 was completely

analagous to that of 38a, consisting of a doublet of

doublets with J F 144.0 Hz. The intriguing question
ab
of exo/endo isomerism will be discussed later in relation

to the 20/20a system, which was studied more extensively.

Also, when 38a (+38) was treated with tri-n-butyltin

hydride at 1000 C, only one product was formed, and was

assigned the exo structure 39 shown below. The 1F nmr


F

a Fa
B a > Hl
r H1
Br Hl
38a [20a] 39 [35]

F 93.3 [92.6] F 108.7 [105.0]
a a


Fb 129.5 [136.2] Fb 142.6 [143.4]



chemical shift data for 38a and 39, as compared to the

analagous data for 20a and 35 (from the furan series, see

Scheme II), shown in brackets above, speak favorably for
35
both 38a and 39 to be exo. Law and Tobey5 observed con-

siderable internal consistency in their data, and used this

as an argument for like stereochemistries in their compounds.

Even though their assignments appear to be reversed, the
19
trends in the data are still useful. Similarity of 1F nmr

chemical shifts can be quite valuable in settling questions

of stereochemistry, but in order to be of any value, the









19
individual 1F resonances must be assigned to the proper
19
F atoms in the proposed structure. Therein lies another

advantage of converting the methine cyclopropyl Br atoms

in adducts such as 20a or 38a to hydrogen atoms as in their

reduced counterparts 35 and 39. Assignment of the 19F cis-

vicinal coupling constant to these protons is simply a

matter of finding the 1F resonance with a large (10 15

Hz) JFH cis-vic. The 1F trans-vicinal coupling is small

(1 2 Hz) but also measurable in the 1F nmr spectrum.

This general method of confirming 1F nmr assignments was

used throughout this work, and as a result, the 1F nmr

assignments in Table IX should be accurate.

If the phenyl groups in 39 were replaced by hydrogens

the resulting compound would provide an opportunity for

measuring coupling between the bridgehead protons and the

methine cyclopropyl protons, which would be useful in making

stereochemical assignments. This system would have a simple

H nmr spectrum, showing only three well separated signals,

and thus would also lend itself to facile W1/2 measurements
19
in both the normal spectrum and the 1F decoupled spectrum.

Of course, this hypothetical system corresponds to the [4 + 2]

cycloadduct of 15 with the parent isobenzofuran. The method

of choice for generating isobenzofuran in situ and the one

that we employed in our reaction with 15 was that of Warrener,52

as shown in Scheme IV. The [4 + 2] adduct 40 was immediately

suspected of being exo on the basis of the 1F nmr chemical

shifts when they were compared to other "known" compounds, as









Scheme IV








OOC







F
15 + a BrF
Br
H Br
40



discussed previously. Once again, reduction of 40 to 41

with tri-n-butyltin hydride allowed confirmation of the
19
F nmr assignments and thus lent support to the exo



F 133.9 H Fb 143.8
F 100.9 F 110.2
/ a a
Br H H1

Br 2 H
40 41


structures shown for 40 and 41.

Additional evidence for structure 41 was obtained from

its 1H nmr spectrum, which consisted of an aromatic AA'BB'

multiple, a doublet for the bridgehead protons (H2), and

a doublet of doublets for the methine cyclopropyl protons

(H1). Since the signals for H2 and H1 were widely separated,









W1/2 for them was easily obtained. In the undecoupled

spectrum of 41 W1/2 for each half of the 112 doublet was

1.0 Hz, in agreement with the expected small value for

JHIH if 41 were exo. When Fb was irradiated, the H2

double collapsed to a sharp singlet, and the doublet

of doublets for H became a doublet, retaining only the

larger cis-vic coupling (JF ). Conversely, when Fa
al
was irradiated, the H2 doublet was unchanged, and the

remaining doublet for H1 showed only the small trans-vic

JFbH2. This experiment demonstrated the utility of hetero-
b2 19
nuclear decoupling in confirming F nmr assignments as

well as determining the extent and nature of long range
19 1
1F H couplings, and by performing such an experiment

on 41, we confirmed that our W1/2 measurement of 1.0 Hz

for JH1H2 was a maximum value.
12
The use of nmr shift reagents with compounds in the

general class we were studying seemed to be appropriate,

since, as a rule, the rate of shift of a given 1H resonance

is inversely proportional to the distance between the

lanthanide metal atom and the proton in question. In com-

pounds such as 41, with two possible stereoisomers, it was

hoped that the rates of shift for exo vs endo protons could

be correlated, once the corresponding rates for a compound

of known stereochemistry had been ascertained. As our

reference compound, 34 was used since it had the prerequisite

oxygen bridge (for a Eu(FOD)3 metal coordination site) as

well as protons on the cyclopropane ring that were known to









be endo (for details of the method, see Experimental). A

comparison of the rates of shift (k) for protons in 34

and 41 is given in Table II. The overall trends in the


Table VI

Comparison of Eu(FOD) nmr shift results for 34 and 41


34


k
avg

0.774

1.74

0.603

0.645


k
avg

0.436

3.97

0.00

0.0064


data of Table II are in agreement for exo structures 34

and 41, in that the signal for H2 in both compounds exhibits

the highest rate of shift. Also, k for 34 and for 41 is

much smaller than kH, but if the kH /klH ratio is calculated,
2 2 1
it has values of 2.25 for 34 and 9.11 for 41. In quantitative

comparisons of this type, a closer correlation would be de-

sirable and necessary if the method is to be more generally

applicable.

The discrepancy in k1 /kH for 34 and 41 is most probably
2 1









due to a difference in the geometry of complexation of

Eu(FOD)3 by the two compounds. It is known that Eu(FOD)3
19
will weakly coordinate to 9F (and produce contact shifts

in the 19F nmr spectrum),53 so that weak secondary coordi-
19
nation with 1F in 34 and 41, as shown below, might cause

a slight off-centering of the Eu atom with respect to the


Eu(FOD) Eu(FOD)

/ / '
/ F H
I 2 F H F
H F /
4 j 1 H 31
113 2 H
3 H14 2 l1
3
34 41


oxygen bridge, with the Eu atom residing more of the time

syn to the cyclopropane ring. If this is the case, the

similarity of kH and k4 in 34 comes as no surprise, nor

do the negligible values for kH3 and kH4 in 41 seem unusual.
3 "4
Speculations of this type may provide satisfying explanations

in individual cases such as the ones above, but these same

rationalizations undermine the generality of the method.

However, the other evidence obtained from W1/2 measure-

ments and heteronuclear decoupling experiments plus the

chemical analogy between 40, 41, and similar compounds known

to be exo leaves little doubt that 40 is the exo adduct of

15 and isobenzofuran. As an interesting sidelight, 41 can

also be recognized as a precursor to l,l-difluoronaphtho-

cyclopropene (42), with the proposed conversion formally














F

F


H1

41


2F
42 F2



42


considered as an overall loss of water from 41. Vogel

et al.,54 had previously prepared 1,1-difluorobenzocyclo-

propene (43), so that 42 would be an interesting extension



F2


43


of these authors' investigation into the question of bond

fixation in benzo-annelated cyclopropenes. The actual

conversion of 41 to 42 was thought possible in light of

recent work55 in which 1,2,3,4-tetrahydronaphthalene-l,4-

endoxide was converted to naphthalene with triphenylphosphine

dibromide via an intermediate dibromo compound, as shown

below. Under the conditions of the reaction of 41 with


N 03PBr Br_

0C1, 90aC


SiO2
_ _2


+ 03P=0


triphenylphosphine dibromide and subsequent silica gel










chromatography, the oxygen bridge was indeed cleaved, but

with concomitant ring opening, so that the only isolated

product derived from 41 was not 42, but B-bromodifluoro-

methyl)naphthalene (44). That the gem-difluorocyclopropane



4 42 ,CF2Br

4 1 4 4- 4 _
44


ring was opened (apparently by Br ) under prolonged heating

was not too surprising due to the probable susceptibility

of the gem-difluoro carbon atom to nucleophilic attack.

Turning to reactions of 15 with acyclic dienes, Law

and Tobey35 had prepared the adduct 45 of 15 with 1,3-

butadiene, which was converted to l,l-difluorobenzocyclo-
54
propene by Vogel and coworkers. Due to the lack of

substituents on the butadiene moiety in 45, the stereo-

chemistry of addition is irrelevant, but there still exists

the possibility of conformational isomerism. Law and Tobey35
19
represented 45 as 45b only, based on the 1F couplings to


H2
Br > Br
S Br H2 Br

F F H2 F

45a 45b


the methylene protons (see Table I According to these









authors, 45b has fewer steric interactions than 45a

and is thus the preferred conformation. Of relevance to

our work is their comment that the J 9FH data seem to
F H
indicate that 45 exists in a "flip form opposite..." to

the conformation of this structure if an oxo- bridge were

present. That is, the bicyclic moiety in 45 appeared to

them to be opposite in structure to this same group in the

furan adduct of 15. However, since the furan adduct (20a)

is in fact exo, their analysis would lead to a prediction

of the less stable conformer 45a as the species most con-

sistent with the nmr data.

In order to resolve this question of stereochemistry,

if possible, and to investigate a cycloaddition of 15 to

an acyclic, unsymmetric 1,3-butadiene for comparison to

the furan series, we elected to use 1-methoxy-l,3-butadiene

in a reaction with 15. The presence of the methoxy sub-

stituent introduces the possibility of stereoisomerism in

the adduct 46, in addition to the previously existing

possibility of conformational isomerism in each stereoisomer.

The resulting four possible structures for 46(a-d) are shown

below, and are classified as exo or endo with respect to the


OCH3 H
H H
Br Br

/Br / H Br
F OCH3 F
exo methoxy endo methoxy
46a 46c
















exo methoxy endo methoxy
46b 46d

46a 46b

46c 46d


placement of the methoxy group. Due to steric repulsions,

the folded forms 46a and 46c would be expected to be less

stable than 46b and 46d. Therefore the choice of which

isomer was actually produced in the reaction was narrowed

to one of the latter two structures. The 1F nmr spectrum

made it possible to assign 46b as the correct structure,

since F (at lowest field) appeared as a doublet of triplets

(JF F = 155 Hz, JF H = JH = 3.2 Hz) and Fb appeared as
ab aa ax
a double of doublets (JFbHb = 2.4 z), as shown below with
19 b
the observed F chemical shifts. The analogy between JF
b b

Ha Fb 138.51 (d of d)


Fa 113.92 (d of t)

Br
OCH Br
3 Br

46b




in 46b (2.4 Hz) and FFbH in 20a (2.1 Hz), shown by the

darkened lines below, and the larger value for the triplet

coupling JF H (3.2 Hz), which was not possible in 20a,
a x,a














F a

OC 3 \
2 Br Br

20a 46b



19
of course, argued for structure 46b. The 1F nmr assign-

ments in 46b were confirmed by reduction of the methine

cyclopropyl bromines with tri-n-butyltin hydride, which

produced the dihydro compound 47 which had the characteris-
19
tic triplet for F in the F nmr with cis-vic coupling
a
JF H of 14.0 Hz. Unfortunately, the remainder of the 19F
ac

H
a F
(n-Bu)3SnH b b
46b > /1//X a
(t-BuO)2 H, A
CH3 c
c
47



nmr spectrum, as well as the 1H nmr spectrum, proved to be

too complex to allow further evaluation of other coupling

constants. Interestingly, a minor artifact of the reduction

was a monobromo product, which could be identified as 48

using 1H nmr chemical shifts and 19F- H coupling constants.

The chemical shift of Hx (64.16) in 48 was quite close to

that of H in 47 (53.91). However, Ha,b in 48 appeared at

62.87, shifted downfield more than 0.5 ppm by the vicinal

cyclopropyl bromine atom, relative to Ha,b in 47, which
3 iu -














a J F =161.0
11H Fb ab
F JF = 15.0
46b > 47 + / x 'Bra ac
J =3.35
OCH3 H a x,a
c
48



19
appeared at 62.33. Also, F in the F nmr spectrum of

48 appeared as a doublet (J = 161.0 Hz) of doublets
ab
(JF H = 15.0 Hz) of triplets (JF = 3.35 Hz), and
a c 19 a x,a
was the F at lowest field (697.74). The monobromo

product which best fits these data is 48. Therefore, the

results obtained for the reaction of 15 with 1-methoxy-l,3-

butadiene correspond to an exo cycloaddition, assuming that

l-methoxy-l,3-butadiene is trans. Also, this reaction

demonstrates that information regarding stereochemistry of

[4 + 2] additions of perhalocyclopropenes to acyclic 1,3-

dienes can be obtained if the diene has a nonsymmetric

substitution pattern. Correct deduction of the product

structure will give an indication of relative conformational

stabilities and may provide clues as to the structure of the

transition state leading to the observed product. But quan-

titative evaluation of all of the steric and electronic

factors in a [4 + 2] cycloaddition reaction such as the one

above is a complex undertaking, so that care must be taken

not to attribute total control of the transition state geometry

to any single factor, excluding other subtler influences










which may be the real controlling factors.

As outlined in the Introduction, alkyl- and aryl-

cyclopropenes have been known to react with fulvenes in
17,18
a [4 + 2] manner, 8 and the resulting adducts can be

further modified to give materials that are useful in

structure-reactivity studies such as solvolysis of alcohol

derivatives and ketone decarbonylation. Specifically,

Tanida,7 using a 6,6-dimethylfulvene and cyclopropene,

synthesized endo-tricyclo[3.2.1.02'4]octan-8-one (50) by

way of oxonolysis of the 8-(dimethylmethylene) compound 49.






1) 03


2) Zn, H

49 50



Since we had previously demonstrated that the methine cyclo-

propyl bromines in some of the furan adducts we had prepared

could be reduced with tri-n-butyltin hydride, the application

of the technique could be used in the synthesis of a 3,3-

difluoro derivative of 50, as shown in Scheme V. It should

be noted that even though 50, derived from cyclopropene and

6,6-dimethylfulvene, was proven to be endo by Tanida, the

assignment of stereochemistry to 51a and 51b must be based

on more than analogy to the hydrocarbon system. Also, our

reactions to form 51a and 51b were run at 1150 C, in contrast









Scheme V

RT R -R

"R Br Dj Br
15 + R F2 F

F2 2

R = 0, CH r r
51a, R = 0 52a, R = 0

51b, R = CH3 52b, R = CI3




R ---R


52a (n-Bu) SnH 1) 03
3 3
52b 2 F2
(t-BuO)2 2) Zn,
H H+ H
53a, R = 0
54
53b, R = CH3




to Tanida's work, which was done at room temperature or

lower. This fact combined with the much greater ground
35
state stability of 15 over cyclopropene means that our

adducts were formed under conditions that may have been

conducive to reversible formation of the more stable exo

adducts.

Since adducts 51a and 51b are the first reported

products arising from a [4 + 2] reaction of a fulvene with

a perhalocyclopropene, stereochemical assignments cannot be
19
based on F chemical shifts observed in these compounds

without reference data for model systems of known stereo-

chemistry. However, since these adducts were treated with









the same reagents as was 20a, and since certain trends in
19
the changes in the 1F nmr spectra of products derived

from 20a were noted earlier, some internal comparisons can

be made in the sequence 51a,b:52a,b:53a,b. As shown in

Table VII, the chemical shifts for F in 52a and 52b are
a -
virtually identical, as are the analagous values for 6F
a
in 53a and 53b. This indicates the similarity in the


Table VII
19
Comparison of 9F Nmr Chemical Shift Data



r- F b r-- F -


Fa a a
/ 'Br aBr a 1H a
Br Br
51a 52a 53a

6F 94.48 111.34 124.80
a

6Fb 131.96 132.65 142.77




CH -CHCH F CH3 -CH3 F CH3---CH3 F




Br Br H
Br r
51b 52b 53b

6F 110.56 124.14
a
6Fb 136.03 146.75









environments for Fa in each of the pairs of compounds.

Turning to the values for 6Fb, if both 51a and 51b were

endo, the differences in the changes in chemical shift

for Fb should also be small, but what was observed proved

to be substantial differences in the values for 6Fb, when

comparisons were made for 52a and 52b, or 53a and 53b.

This indicates rather dissimilar environments for Fb in

these compounds, whereas the environments for F in the
a
same compounds were shown to be quite comparable. If both

adducts were endo, the values of 6Fa and 5Fb ought to be

almost identical for 53a and 53b, as shown below, instead



0 CH3-..-CH3





AF F
Fb a Fb a

53a (as endo) 53b (as endo)


of exhibiting the differences shown in Table III. Therefore,
19
based on these internal comparisons of 1F chemical shift

values, adducts 51a and 51b appear to be exo. The other

criteria useful in specifying stereochemistry are not as

applicable in these two cases. First, the observance of

or the lack of coupling between bridgehead protons and methine

cyclopropyl protons in 53a and 53b is obscured by the fact

that the bridgehead protons in 52a and 52b, and 53a and 53b,

all appear as broad multiplets. All that can be said is that










W1/2 for 52a and 53a are both 6 Hz, and that W1/2 for 52b

and 53b are both 5 Hz. While these W1/2 values for 53a

and 53b could accommodate a coupling of 3-4 Hz for bridge-

head proton-methine cyclopropyl proton coupling, the fact

that the values do not change upon debromination is

supportive of the proposed exo structures. Also, the

complexity of the H nmr spectra and the extensive H H

couplings in these compounds renders heteronuclear decoupling

almost useless, since the values for W1/2 would not change
19 1
much even if all 1F H couplings were eliminated. While

a Eu(FOD)3 experiment might be of some help in assigning

stereochemistry in the ketone 54, it must be mentioned that

no Eu(FOD)3 shift data are available for the known epimeric

ketones in the non-fluorinated series for comparison, so that

this technique is of limited utility. Until such data are

amassed, both for model systems (for example, exo- and endo-

tricyclo[3.2.1.0 24]octan-8-one) and for ketone 54 (as of

this writing, 54 has not yet been characterized), the only

indications that both 51a and 51b are exo adducts are chemical

intuition (in light of the severe reaction conditions) and
19
more importantly the 1F nmr chemical shift behavior discussed

above. If 54 does, indeed, prove to be exo, the synthesis

of the epimer, endo-3,3-difluorotricyclo[3.2.1.024 ]octan-

8-one (55), required for investigations into the effect of

fluorine substituents on reactivity in the tricyclo[3.2.1.024]-

octyl system, becomes much more difficult, since the exo isomer

(54) should be obtainable by alternate routes. Also, as will

















F
F
55

be discussed later, endo 55 may easily isomerize to exo

54 at moderate temperatures.

At this time, and taking into consideration the results

discussed above for the reactions of 15 with 6,6-diphenyl-

and 6,6-dimethylfulvene, the next logical step in our

stereochemical studies of the [4 + 2] reactions of 15 seemed

to be an attempt to force this cyclopropene into reacting

with a diene so as to produce an endo adduct. The diene we

chose was spiro 4.2 heptadiene (56), since the spiro methylene

groups would appear to place severe steric restrictions on

any cyclopropene reacting via the exo mode (see below).


O a.l0





56






Substantial non-bonded interactions should develop between

the cyclopropene methylene substituent and the apical cyclo-

propane hydrogens syn to the reacting cyclopropene molecule.

On steric grounds, then, an argument might be made for the









reaction of 56 with 15 to proceed to give an endo adduct.

Also, the adduct of cyclopropene with 56 was reported by
22
LaRochelle and Trost to be endo, based on the similarity

of its 1H nmr spectrum to other endo adducts of cyclo-

propene. Conversely, and also on chemical grounds, the

exo adduct (57a) of 56 and 15 may well be the more thermo-

dynamically stable isomer, despite the steric interactions

mentioned above. The reaction of 56 with 15 was initially




F


Br

F Br
F

57 57a


attempted in CC14 at 550 C, but the reaction was sluggish

at the concentrations used, so that prolonged heating at

55 C proved necessary for complete reaction. Nevertheless,

57 (57a) was isolated, and the spectroscopic and analytical
19
data for it were accumulated, including the 19F nmr chemical

shifts. The technique used previously to firmly establish
19
F nmr assignments, that is, reduction of the methine cyclo-

propyl bromines with tri-n-butyltin hydride, was again applied

to adduct 57 (57a), to give 58 (58a). At this point, we had
19
firmly established 1F chemical shift data for both the adduct

and its debrominated product, as well as 1H nmr data for both

compounds. The chemical shift data alone for these two










compounds do not allow for the unambiguous assignment

of exo or endo stereochemistry, but comparison of these

data to data from the adduct of 15 with cyclopentadiene

of known exo stereochemistry leads to the tentative

assignment of exo stereochemistry in this case (that is,

57a and 58a).

First, measurements of W1/2 for the bridgehead protons

in 57a and 58a gave values of 7 Hz and 6 Hz, respectively,

indicating that any coupling from the methine cyclopropyl

protons to the bridgehead protons in 58a is most likely

small. Also, in a homonuclear decoupling experiment on

58a, when the bridgehead protons were irradiated, the

methine cyclopropyl proton doublet maintained a line width

of 3 Hz, which again is contraindicative of significant

coupling of the type mentioned above. Second, a hetero-

nuclear decoupling experiment on 58a, in addition to con-

firming the assignments of Fa and Fb, revealed an interesting

six bond coupling from one fluorine to only two of the four

apical cyclopropyl protons. When F in 58a was irradiated,
a
the doublet signal for the methine cyclopropyl protons

collapsed to a broad singlet (W1/2 = 3.9 H1z), as expected,

and no change was observed in the complex pattern for the

apical cyclopropyl protons. However, when Fb was irradiated,

the W1/2 for the methine cyclopropyl doublet decreased to 2.4

Hz as expected (note that this again indicated small coupling

to the bridgehead protons), but of more interest was the

change in the spirocyclopropyl proton signals. The upfield









group of three broadened lines, which remained unchanged

when either Fa or Fb was irradiated, were assigned to the

two protons anti to the gem-difluorocyclopropyl group and

situated above the double bond. The downfield group of

six broad lines collapsed to three lines when the F

coupling was removed, and measurement of JF placed a
19 1 b syn
value of 4 Hz on this long range F H coupling. If 58a

were endo (that is, 58), as depicted below, with the

observed JFH outlined, the alternate long range coupling



H H H H H H
H H H H H H






Fa F F
b b a Fb a
58

"observed" JF H alternate, unobserved JFH
b syn

as either J ai or even J H, should at
b anti a anti, or syn
least have been observed in the decoupling experiment.

Similar analysis for the proposed exo structure 58a, as

shown below, reveals that Fb is in much closer proximity to

the syn protons, to which it is coupled, than Fa, which is

H. H H H ,H
H H H H Fb H V H F

F F
a FaF /a


58a

"observed" JF H alternate, unobserved JFH
b syn









situated away from both the syn and anti spirocyclopropyl

protons. All of these observations can be correlated by

the application of an empirically derived rule stemming

from observations of long range F H coupling made by
e 56,57,58
Cross et al.56 8 For example, the observance of five

bond coupling in 6-fluorosteroids is dependent on whether
19
the F atom is a or 8, as shown below. In 59, the -CH3


H
H
H H H H
1 1




6


59 (68-F) 60 (6a-F)

resonance appears as a doublet, whereas in 60, no observable

coupling of this type occurs. Also, in the 5S, 68 -difluoro-

cyclopropyl steroid 61, the methyl resonance is a doublet,

indicating coupling to one, but not both, of the gem-fluorines,

which is rather analagous to the situation seen for the exo

compound 58a. Finally, in the cyclobutane 62, only Fb is

observed to be coupled to the methyl group (which is in accord


H
62









with the previous data if the conformation shown above

is strongly preferred).

All of the above data were condensed into a rule,

useful for predicting long range F II coupling, which
19 1
states that 9F H coupling will be observed only

when a vector directed along the C-F bond and originating

at the carbon atom can converge upon and intersect a

similar vector directed along a C-H bond of the methyl
59
group." In fairness, this rule is not totally applicable

to 58a, since the C-Fb vector bisects the angle formed

by Hsyn-C-Hsyn, and does not directly intersect either

C-H vector. However, since this coupling is most likely

a through-bond effect, the simple convergence of the C-Fb

and C-Hsyn vectors may make the use of the rule justifiable

for 58a. The six bond coupling that we observed in 58a

is, in our opinion, the first example of the type of long

range JFH designated by Jefford60 as intercalatedd". That

is, in the intercalated arrangement the C-F vector bisects

the H-C-H angle (as in 58a), whereas in the "opposed" mode,

the C-F and C-H vectors intersect. The intercalated and

opposed orientations as designated by Jefford6 for 5J

are shown below.


H F HF
H H

H


intercalated


opposed









A third indication of exo stereochemistry in 58a

19
comes from comparison of the 1F nmr chemical shifts for

57a and 58a with the reference system obtained from the

[4 + 2] cycloaddition of 1,2-dibromo-3,3-difluorocyclo-

propene (15) with cyclopentadiene, which at room tem-

perature gives only the exo adduct 63, which can be

converted to 64 (also exo) by the use of tri-n-butyltin

hydride, as shown. (The arguments for exo structures 63




15 + F F
"Br H

Br H
63 64



and 64 will be given later and in relation to data from

other reactions.) The comparative 1F nmr chemical shift

data are shown in Table VIII. What is pertinent is the


Table VIII
19
Comparison of 19F Nmr Chemical Shift Data





F 124.10 F 127.82

F 81.94 F 81.07
a a


57a Br
57a









Table VIII Continued




F 131.72 F 139.32

F 100.30 F 100.12


1 a H
58a 64


similarity in SF for 57a and 63, and 58a and 64, which

in turn indicates the similarity of the environments for

Fa in these compounds. The much larger discrepancies for

6Fb in 57a and 63, and 58a and 64 are due to the differences

in the bridge substituents in the two systems. In summation,

then, 57a and 58a appear to be the most probable structures

for the cycloadduct of 15 and 56, and for the product derived

from the reduction processes, even though on steric grounds

the endo structures (57 and 58), in analogy to the cyclo-

propene adduct of 56, were thought to be the more likely of

the two isomeric possibilities.

As mentioned above, the [4 + 2] cycloadduct 63 of 15

with cyclopentadiene was prepared in CCl4 at room temperature.

At first, the crude reaction mixture was catalytically reduced

to 65 to prevent decomposition, but subsequently it was found

that 63 could be purified by distillation at reduced pressure

and fully characterized. In addition, both 65 and 63 were

treated with tri-n-butyltin hydride producing 66 and 64,

respectively. Finally, the phenyl azide adduct (67) of 63,

was prepared. These transformations are illustrated in Scheme









VI. The exo stereochemistry of 63, 64, 65, 66, and 67


Scheme VI



Fb Fb
H 2'Pd/C (n-Bu)3SnH
a --- ------ a2
0OoC 'Br (t-BuO)2

63 Br 65 r





Fb F
Fb b
(n-Bu)3SnH Fa F
SFa
(t-BuO) /2

64 1 66 1


Fb
N3 F
"'Br


67


was unambiguously established by an authentic synthesis of

66, to be discussed later. The H nmr and 1F nmr spectra

of 63 exhibited some4unusual features worthy of detailed
19
analysis. As expected, in the F nmr spectrum F appeared
a
at lowest field as a doublet (W-/2 = 3.6 Hz; JF F = 145.5
ab
Hz), and in accord with earlier observations was assigned

the position cis to the methine cyclopropyl bromine atoms.

This assignment was confirmed in the usual manner after re-

duction with tri-n-butyltin hydride. On the other hand, the









Fb resonance, at highest field, was a doublet (JF F ) of
ab
quartets of doublets. The quartet coupling was 3.2 Hz

and the doublet coupling was about 1.2 Hz. Coupling of

3 Hz from Fb to the bridgehead protons (H2) agrees with

our earlier data, and an additional (and coincidental)

coupling of 3 Hz from Fb to Hsyn' as shown below, is also

reasonable when the long range coupling discussed earlier

is considered and the "C-F vector- C-IH vector" rule is

recalled. This argument leaves only a 1.2 Hz coupling to




anti syn b 1 = 3.2 Hz
2 F b2 FbHsyn

Br F b H a = 1.2 Hz
L b anti
2 Br

63



Fb to be accounted for, and the most likely mode of coupling

is the five bond coupling JF as shown above. Turning
1 b anti
to the H nmr spectrum of 63, the assignment of the low

field half of the bridge protons' AB system at 62.02 to anti
anti
and the high field half at 61.32 to H is based on the
syn
expected shielding of H by the cyclopropane ring. The
syn
doublet for Hanti had a W1/2 = 4 Hz with J 9.6 Hz.
syn anti
The signal for Hsyn appeared as a doublet of doublets of

triplets. As before, J = 9.6 Hz, and JF Hs = 3.2
syn anti b syn
Hz, leaving only the triplet coupling to be accounted for by

JH H = 1.8 Hz. Also, in a decoupling experiment, when the
syn 2









H2 signal was irradiated, the triplet JH coupling was
syn 2
removed, leaving a doublet (JH H = 9.6 Hz) of doublets
syn anti19
(J = 3 Hz) for the H resonance. The long range F -
FbHsyn syn
H coupling detailed above was also visible throughout the

series 63 67 whenever the signal for H was separated
- syn
from the rest of the spectrum.

These findings are somewhat in contrast to long range
19 1
19F H coupling data reported for the analagous compound

71 by Jefford et al.60 According to their analysis of the
19 1
1F nmr and H nmr spectra of 71, the following coupling

constants were assigned. No mention was made of any coupling



antH Hsyn F JFH = 3.6 Hz
H Jsyn
2 H yn = 3.0 Hz
anti
H JFH = 3.5 Hz
2 1

71


from the fluorine to the bridgehead protons (H2), which is

odd since in our adduct 63, JF H was found to be 3.2 Hz.
Fb 2
Moreoever, the assignment of J = 3.0 Hz in 71 also
FHi
anti
disagrees with our assignment in 63 of J anti = 1.2 Hz.
b anti
Of course, 63 is an unsaturated system, whereas 71, as a

saturated analog, could differ enough in geometry to cause

substantial changes in values for long range JFH'

In summarizing the results of the cycloadditions of

1,2-dibromo-3,3-difluorocyclopropene (15) with cyclic 1,3-

dienes, it becomes necessary to state explicitly what was









merely implicit in the preceding discussion. That is, in

all cases the products that have been characterized represent

isolated, purified substances, which of necessity must

comprise less than the amount of material which would result

from 100% conversion of starting materials. Also, most of

the reactions were run under conditions highly conducive

(as will be discussed shortly) to endo-exo isomerizations.

As a prime example, in the debromination of the 1,3-diphenyl-

isobenzofuran adduct (38a/38), the minor endo component

(38) was either isomerized to the exo compound (38a), or

the endo debrominated species was not isolated during the

workup of the reduction mixture. Therefore, the formation

of minor amounts of endo cycloadducts with 15 is not ruled

out for any of the cycloadductions and in some cases their

actual formation was confirmed (see Chapter II, section III.

Isomerization Studies of Selected [4 + 2] Cycloadducts, p 80).


Carbene Additions to the Bicyclo-
[.22.1-heptyl System


The proof of structure for our Diels-Alder adduct 63,

previously alluded to, consisted of conversion of 63 to 66,

the saturated, debrominated fluorocarbon. It was noted

that this same material, if it were exo, should be accessible

by way of addition of difluorocarbene (:CF2) to norbornene.

This reaction was carried out using the procedure developed

by Seyferth et al.6 for generating difluorocarbene (which

most likely exists as a carbenoid). The material isolated

from the difluorocarbene addition to norbornene had an













63 1 :CF2
_3 -- <---

66


infrared spectrum identical to the infrared spectrum of

66 which was derived from the cycloaddition product of 15

with cyclopentadiene (see Scheme VI).

At this point a brief discussion of carbene additions

to the bicyclo[2.2.1]heptyl system is in order. When a

carbene adds to norbornene, the sole product is the result

of exo addition,6263 due presumably to the steric hindrance

to the endo pathway by the endo-5,6-hydrogens. There have

been reports of halocarbene additions to norbornene, and in

those cases where one or both of the halogens were fluorine,

the thermally stable products (i.e, non ring-opened) were

found to be exclusively exo. For example, fluorochloro-

carbene (:CFC1), produced by the base catalyzed decomposition

of sym-difluorotetrachloroacetone, gave two products, 68

and 69, with 69 arising from the rearrangement of 70.



6 F Cl
:CFCl


H
68 70 69









Similarly, bromofluorocarbene (:CFBr) gave the analagous

products 71 and 72 (with 72 derived from 73.)44 With




:CFBrS
Br -->

H
71 73 72




norbornadiene the steric inhibition to endo carbene addition

is diminished and endo addition products with methylene have

been reported.65'66'67'68'69 Halocarbene additions to

norbornadiene would likewise be expected to give mixtures

of exo and endo products. Two recent papers by Jefford and

coworkers,771 dealing with the results of fluorocarbene

additions to norbornadiene, not only confirmed the possibility

of endo addition in this system, but provided IH nmr data

that proved quite useful in making stereochemical assignments

in related tricyclic systems.
70
In the first paper, exposure of norbornadiene to

difluorocarbene (generated at 800 C) resulted in isolation

of only two products, 74 and 75. Also, when norbornadiene

was reacted with chlorofluorocarbene (:CFC1) at 1400 C, five


7CF F

801c +

74 ~2 75









products were isolated, as shown below. The absence of

any endo-tricyclo[3.2.1.024 ]octyl compounds is not surprising



FF















Cl Cl F
F 1



in view of the stringent reaction conditions (1400 C, 12

hours), as compared to Jefford's later paper,7 which

recounts the results of the reaction of norbornadiene with

difluorocarbene at 200 C.

In a series of experiments performed at 200 C, that

is, under conditions non-conducive to isomerization of any

of the reaction products, Jefford was able to separate and

characterize the difluorocarbene adducts of norbornadiene

and to compare them to the analagous adducts of 7-methyl-

norbornadiene. H and F Nmr chemical shifts and H F

long range coupling data enabled the structures of all

products to be assigned with some degree of certainty.

Norbornadiene and difluorocarbene, at 200 C, form three

1:1 adducts; a homo-1,4-adduct (75), plus exo (74)- and endo









(76)-3,3-difluorotricyclo[3.2.1.02'4 oct-6-ene.





F F
20HC -H

2 F
F

75 74 76



Similarly, 7-methylnorbornadiene forms four adducts

with difluorocarbene; a homo-1,4-adduct (77), as well as

the exo-anti (78)-, endo-anti (79)-, and endo-syn (80)-3,3-

difluoro-8-methyltricyclo[3.2.1.02 4]oct-6-enes, as shown

below. Accurate structural assignments in these tricyclic

H3 .H3 CH- F
CF2



F2

77 78


CH CH





F F F
79 80


adducts were expedited by the presence or absence of long
19 1 5
range 1F coupling, labelled 5JFH by Jefford, amounting

to 8.5 Hz, and present only in those compounds having the









requisite structural features, namely, an endo-gem-

difluorocyclopropane ring and a proton on the bridge

anti with respect to the cyclopropane ring. Similar long
19 1
range 1F H coupling (9.8 Hz) was also observed in the

tetracyclic products 75 and 77, due to the presence of the

same chair cyclohexane 1,4-diequatorial 1F H arrange-

ment, as shown below. Only the endo tricyclic adducts 76

and 80 display long range 1F H coupling of this magnitude.



H H

H

F
F
F



The lack of JFH in 79 is due, of course, to the presence of

the anti methyl group.

If the data presented by Sargeant31 for the cyclo-

addition of 1,3-bis(trifluoromethyl)3,3-cyclopropene (17)

with cyclopentadiene, which was discussed earlier (see

Introduction, section III. Perhalocyclopropenes as Dieno-

philes, p 12 ), is now reexamined with regard to long range

19F 1H coupling, it becomes apparent that the two epimeric

cyclopentadiene adducts of 17 should indeed be assigned the

structures 27a and 28a, as we had suspected earlier. This

reversal of the assignments made by Sargeant is based on the

fact that only 28a (endo) exhibits a JF H of 8.5 Hz, and
af
thus our earlier revision of the exo and endo assignments









was entirely in order.

As a part of this same work,71 Jefford also studied

the thermal behavior of 74 and 76, and found that endo-76

isomerized at 60 80 C to exo-74. Therefore, the fact

that we isolated only the exo adduct 63 of cyclopentadiene

and 15 by distillation is reasonable. Further, as Jefford

points out, the facile isomerization of 76 to 74, plus the

observation of the 8.5 Hz F 1H coupling in 76 only,

leads inevitably to a reassessment of the isomerization work

done by Sargeant31 discussed earlier. Again, as we had

suspected, the reassignment of the stereochemistries of

Sargeant's Diels-Alder adducts to 27a and 28a now makes

their thermal behavior also seem more chemically sound.

Thus, the reaction of 17 with cyclopentadiene and the sub-

sequent isomerizations of the products is most correctly

represented as shown below.
650C

CF F
-78C CF 3 F
CF CF
CF3 FC
3 F CF3
F"
17 28a 27a

(69%) (31%)




C3F2 2000C
C F3

CF
3










Isomerization Studies of Selected
[4 + 2] Cycloadducts


The observation of endo to exo isomerization (76 74)

by Jefford71 under relatively mild conditions (600 800 C)

prompted us to reinvestigate the behavior of 20a under

comparable conditions. Our approach to the problem was

twofold; first, the reaction of 1,2-dibromo-3,3-difluoro-

cyclopropene (15) with excess furan was run at 250, 500

and 750 C. The crude reaction mixtures were then examined

using 1H nmr for completeness and by 19F nmr for the de-

tection of the exo (20a) and endo (20) isomers. The
1 19
structure for endo 20 was evident from the H and 1F nmr

data (see Table IX). The 1H nmr spectra for exo 20a and
19
endo 20 appear to be identical, and the 19F data for endo

20 are consistent only with an unrearranged tricyclic structure

with JFaFb = 143.0 Hz, and JFbH2 = 2.2 Hz. Second, a sample

of 20a, verified by 19F nmr to contain only exo 20a, was

heated at 800 C in the presence of excess furan, and the

19F nmr spectrum of the resulting solution was recorded.

Also, an nmr sample of the exo isobenzofuran adduct (40)

was heated at 800 C for one week and then analyzed by 19F

nmr. The results of these experiments are shown in Scheme VII.

The failure of the isobenzofuran adduct 40 to isomerize is

not too surprising, if the mechanism for exo/endo equili-

bration consists of a retro-Diels-Alder reaction followed by

recombination to give an equilibrium ratio of products. In

order for 40 to undergo such a retro-cycloaddition, the










Scheme VII


250C exo only

500C exo only

750C exo/endo = 2.69/1.0


/ 800C R.T
\XBr > exo/endo = 3.3/1.0 ---> 2.64/1.0

,Br


80c
1 week


exo only


aromaticity of the benzo-moiety in 40 would have to be

disrupted, so that this pathway would seem to be unlikely

to occur with 40.

Second, the likelihood of a retro-Diels-Alder reaction

taking place in the 20/20a system is greater than with 40

due to the small gain in aromaticity if furan were formed


Br
F


Br

15









from either stereoisomer by way of the retro-cycloaddition

pathway. Thus, a possible mechanistic rationale for the

behavior observed for 20a is that this exo isomer, under

prolonged heating, isomerizes partially to the endo

isomer 20 via retro-cycloaddition to furan and 15 followed

by readduction, this process continuing until the 2.7/1.0

exo/endo ratio reflecting the relative thermodynamic

stabilities of 20a and 20 is obtained. The kinetic product

of this cycloaddition appears to be the exo adduct 20a,

since at lower temperatures, 20a was the only product ob-

served in the 19F nmr spectrum.

Since endo-20 is less stable than exo-20a, it is also

reasonable to assume that 20 should undergo a retro-Diels-

Alder reaction more easily than 20a, which helps to account

for the apparent fact that Law and Tobey35 in their original

work did not observe any endo material when they distilled

their crude reaction mixture. The exo adduct, being more

volatile (and also more stable) was the material that they

collected, thus leaving an endo enriched pot mixture, which,

of course, could then have isomerized to the equilibrium

mixture. The net result of these processes would be a net

distillation of only the exo adduct 20a. When we attempted

to isolate the endo material by preparative gas chromatography,

isomerization on the column (at 1000 C) probably occurred,

since we were only able to obtain a sample comprised of

mostly (-60%) endo material. This sample proved to be stable

to further isomerization in the absence of furan and at room









temperature, so that we were able to collect 1H nmr and
19
F nmr data for the endo compound 20.

The isomerizations of some of the other adducts of

15 could be studied by similar techniques, were it not for

the fact that the dienes, once formed in the retro-cyclo-

addition, would tend to dimerize rather than re-form Diels-

Alder adducts with 15. Also, since the isomerizations of

endo adducts to their exo isomers has been shown to occur

under mild heating, the isolation and characterization of

endo products will be difficult.

Therefore, in our proposed syntheses of the epimeric

3,3-difluorotricyclo[3.2.1.02,4]octan-8-ones, the endo

material (55) could well isomerize to the exo isomer (54)

before loss of carbon monoxide could occur, as shown below.

This possibility would make the study of the decarbonylative


9 2





55 2 -k CO /
k k ?
isom -CO
isom -CO ?


reactivity of 55 and compounds derived from them difficult

if the isomerization pathway were dominant.


Synthetic Studies of 3,3-Difluorocyclopropene

One solution to the problem of synthesis of the endo









isomer 55 would be to react 6,6-dimethylfulvene with a

gem-difluorocyclopropene having a greater reactivity than

15, so that a lower reaction temperature (more conducive

to endo adduct formation) could be used in the initial

cycloaddition. The obvious choice for this dienophile is

the parent compound, 3,3-difluorocyclopropene (87), which

has not yet been reported. We have attempted the synthesis

of 87 and one of the more promising synthetic routes we

devised is outlined in Scheme VIII. The reaction of 15


Scheme VIII

Br
Br Br F


+BF
Br
15 81

H F
(n-Bu)3SnH H 2
81



82



H
82 ------> +0



87



with anthracene required prolonged heating at 1300 C, in-

creasing the probability of unwanted side reactions. Instead

of the desired Diels-Alder adduct 81, we obtained the ring









opened isomer 83, which probably arose from the rupture of

one of the peripheral cyclopropane bonds after the initial

adduction of 15 by anthracene had taken place. The H nmr

spectrum of 83 consisted of two singlets for the bridgehead

protons plus a group of complex aromatic absorptions, while

the 19F spectrum consisted of only a singlet at 647.01,

which is consistent with the ring opened structure but

clearly eliminates the original Diels-Alder adduct structure

81. Reduction of the two bromine atoms in 83 could not

produce, of course, the desired compound 82, but instead

gave the ring opened analog 84. The 100 MHz 1H nmr spectrum

of 84 revealed a triplet at 6.1 with J = 56 Ilz, which is

consistent with the presence of a -CF2H group in the mole-

cule. Also, the remainder of the II nmr spectrum, as well

as the 1F nmr spectrum supports structure 84. These trans-

formations, that took place instead of the desired reaction

sequence above, are shown in Scheme IX. Thus, the ring

opening reaction of 81 to give 83 prevented this approach


Scheme IX



0 0 + 15 [81]?-
SBr


83 CF2Br


(n-Bu) 3SnH
83 / H


84 CF2H









from yielding the desired precursor to 3,3-difluorocyclo-

propene (87).

Another promising approach to 87 required the synthesis

of 1,2-bis(trimethylsilyl)-3,3-difluorocyclopropene (86),

by the addition of :CF2 to the alkyne 85, as shown below.

Hydrolysis of the trimethylsilyl substituents should give





Si(CH 3)3
:CF2
2 .
(CH3)3Si-C-C-Si(CH3) ---> F2

Si(CH3)3

85 86


the desired 87. Difluorocarbene addition at 800 C gave

an unstable material in low yield that appeared to be 86,

but this cyclopropene failed to react with any diene,

including isobenzofuran generated in situ. Also, an

attempted hydrolysis of the trimethylsilyl groups, using

a KOH-methanol solution failed to produce 87 or any other

volatile products.










1n

Ln



&-o
a
h
>4














44
0


'-4

0N -
0M

















44
0
0.a
[4







0 o


N O
0 *4
04 0
04 04 0


>0
04043


a

CO CO
[- '-
ID
4 04
N 04
04 n -


14
r4 -. r
m


co
0


















> 0


co Tr



0 -4 4 f
N In
04 10






mm >.






> \>4

= s;
044


04


0 CN
I II


m


1-1 i-i


'0.0




0a 4

o o

v v


+

.0

0l'O '0 '0 1


04
N~m








I o N~ <4 04
[0 <04 ,-4 N F

rN 11n [1 '











CN

Ln
r (N
II II II
.Q N

1-; 1-;


S' n LO (
0m co H o


* 0
0D (n On


II II 11 II



-1 I-h 1) r


( LN

> r 0 (
LOD
r- --I -I N




















0 0







(N Ta
ii- in





(N (N

M+
(1 + 41




(N HVU H-
0 aI
(, qL

UtE


q4

0






co Cn 0)







--I
.L H
WIl
(N
r(


0
In
in ) r- C



-D D D -
II ii II II
.0 H H N
WI ao
04 0 .


(m N l


J 0 '4-
X -O 0







So o to





~m





(


~(N(N (N


a ,Q


4 1O
0 0

0


4J 4i


0 0

'0'0r


NU


I




0
cr tj










o in



Sr-
II


F:
bo


II



c4
F-


-U
4J
44 L
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Full Text

PAGE 1

STRUCTURAL STUDIES OF [4 + 2] PERHALOCYCLOPROPENE CYCLOADDUCTS By ROBERT GILES POSEY A DISSERTATION PRESENTED TO THE GRADUATE COUNCIL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 1975

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To Phyllis and Will

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ACKNOWLEDGEMENTS The author wishes to thank Professor Merle A. Battiste for directing this research, and for his continued interest in and support of a research project which became a learning experience for all concerned. Dr. Battiste is to be commended for displaying the intellectual flexibility so vital in the pursuance of research. The author also wishes to thank the rest of his supervisory committee for their part in the course of this work, and especially for their cooperation during the weeks in which this dissertation was prepared. Appreciation is also expressed to Dr. Wallace Brey and the members of his research group for their help in obtaining some of the data used in this study. Also, partial financial support from the Department of Chemistry in the form of teaching assistantships was appreciated. Finally, the author's family deserve special thanks for providing unfailing support and encouragement throughout this project.

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TABLE OF CONTENTS Page ACKNOWLEDGEMENTS iii LIST OF TABLES v ABSTRACT vi CHAPTER I INTRODUCTION 1 Diels-Alder Reactions General 1 Alkyland Aryl-Cyclopropenes as Dienophiles 5 Halocyclopropenes as Dienophiles 12 Objectives of This Work 31 CHAPTER II RESULTS AJ^D DISCUSSION 3 4 Stereochemical Studies of Perhalocyclopropene [4+2] Cycloadducts . . . . 34 Carbene Additions to the Bicyclo[2. 2, l]-heptyl System 73 Isomerization Studies of Selected [4+2] Cycloadducts 80 Synthetic Studies of 3 , 3-Dif luorocyclopropene 83 CHAPTER III EXPERIMENTAL 98 General 98 REFERENCES 142 BIOGRAPHICAL SKETCH I47

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LIST OF TABLES Table p^ge 1 19 I H and F nmr Data for 2J^ and 22^ 18 1 19 II H and F nmr Data for 21a 20 1 19 III H and F nmr Data for 22a 21 1 19 IV H and F nmr Data for 26_, 2_7, and 28_ 24 1 19 V H and F nmr Data for 27a and 28a 28 VI Comparison of Eu(FOD) nmr Shift Results for 34 and 41_ : 49 19 VII Comparison of F nmr Chemical Shift Data 59 19 VIII Comparison of F nmr Chemical Shift Data 68 1 19 IX H nmr and F nmr Data 87

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Abstract of Dissertation Presented to the Graduate Council of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy STRUCTURAL STUDIES OF [4 + 2] PERHALOCYCLOPROPENE CYCLOADDUCTS By Robert Giles Posey December, 1975 Chairman: Dr. Merle A. Battiste Major Department: Chemistry Previous literature reports of exclusive formation of endo [4+2] cycloadducts of perhalocyclopropenes with furan were shown to be in error by a single crystal X-ray structural analysis of the phenyl azide adduct 3_2 of 2 , 4-dibromo~3 , 3difluoro-8-oxatricyclo[3.2.1.0 ' ]Oct-6-ene ( 20a ) , which revealed the exo stereochemistry of the gem-dif luorocyclopropane ring in 32_, and thus in 20a . Using exo-20a as a model compound, a series of chemical transformations were carried out in order to establish H nmr and F nmr parameters to be used for the determination of stereochemistry in unknown systems. In addition, heteronuclear decoupling, measurements of line widths at half-height (W. ,^) / and Eu(F0D)3 nmr shift experiments were carried out on 20a and

PAGE 7

the series of compounds derived from 20a , of which all were known to possess exo stereochemistry. New [4+2] cycloadducts of 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15) were prepared with 1 , 3-diphenylisobenzofuran, isobenzof uran , 6 , 6-diphenylf ulvene , 6 , 6-dimethylfulvene, spiro[4.2 heptadiene, cyclopentadiene, and the acyclic diene 1-methoxy-l, 3-butadiene . By the application of chemical transformations as well as the spectroscopic techniques previously mentioned, it was shown that under the reaction conditions used, the cyclic dienes formed exclusively exo [4+2] adducts with ^ as isolated products. In the adducts of 15_ with cyclopentadiene and spiro[4. 2] heptadiene (63_ and 52a), substantial long range "^^F ^H coupling was observed in the ^H and "'"^F nmr spectra, and this phenomenon was part of the evidence used for the assignment of exo stereochemistry in these compounds. This 5 6 Jpj^ and Jpji coupling was compared with previous literature reports, and in the case of the spiro [ 4 . 2 ] heptadiene adduct (57a.) constitutes the first example of the intercalated mode of long range ""-^F -""H coupling. Having established the exo stereochemistry for the [4 + 2] cycloadducts of 15^ formed at relatively high temperatures (80° 115° C) , the behavior of adduct 2_0a was examined at various temperatures. As a result, it was found that only exo 20a was formed at lower temperatures, but that at 75 80 C, an equilibrium mixture of exo 20a and endo-20 19 could be detected by F nmr. The adduct of 15 with iso-

PAGE 8

benzofuran was found by 'F nmr to retain the original exo orientation after prolonged heating at 80° C. As part of the attempted synthesis of the epimeric exo (5_4)and endo (55^) -3 , 3-dif luorotricyclo [ 3 . 2 . 1 . 0^ ' '^ ]octan-8-ones, the synthesis of the previously unknown 3,3-difluorocyclopropene {81) was attempted. In one such attempt, the product of the reaction of 1_5 with anthracene at 130 C was shown to be a ring opened species. In another attempt at the preparation of 81_, the unstable 1,2-bis(trimethylsilyl) 3, 3-dif luorocyclopropene (8_6) was prepared, but the attempted conversion of 8_6 to 87 by hydrolysis failed to give any volatile products.

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CHAPTER I INTRODUCTION Diels-Alder Reactions General Reactions between conjugated dienes and olefins have been thoroughly investigated and have become quite important synthetic tools in organic chemistry.-'The reaction products are either mono-, bi-, or tri-cyclic, depending on whether the diene and/or dienophile are cyclic or acyclic, as shown below. Such reactions were first extensively utilized by Diels 2 and Alder, beginning in 1928, and since then the mechanistic aspects of the Diels-Alder reaction have been probed by a number of workers. Various effects of substituents ,

PAGE 10

catalysts, and solvents as v/ell as steric and electronic factors were reviewed by Seltzer. Of course, the DielsAlder reaction may be viewed in terms of the Woodward4 Hoffmann orbital symmetry treatment. As illustrated in the following correlation diagram, Diels-Alder cycloadditions are thermally allowed processes, with the likelihood of reaction and structure of products controlled by substituents on both the diene and the dienophile. <^a3^c + + — A^ \i°^^" In those Diels-Alder reactions where the possibility of stereoisomerism exists, predetermination of reaction product stereochemistry is not always as simple as merely applying the Alder endo rule. This rule states that the reacting species, when arranged in parallel planes, will react via the orientation which has the "maximum accumulation" of double bonds, which includes all double bonds in

PAGE 11

both the diene and the dienophile. The endo -addition rule is illustrated below for the reaction of maleic anhydride with cyclopentadiene , which proceeds to give > 98.5% endoadduct and <1.5% exo -adduct . Indeed, the majority of <1.5% >98.5% cycloadditions betv;een cyclic dienes and cyclic dienophiles obey the endo -addition rule. However, the endo -addition rule is applicable to kinetically controlled phenomena, and does not necessarily reflect the relative thermodynamic stabilities of stereoisomeric products. In the example shown below, the endo-adduct of furan and succinimide isomerizes upon v^arming to the more thermodynamically stable exo isomer. Analagous behavior, i.e., facile cycloreversion 25° 90° of the endo isomer followed by addition to give the

PAGE 12

thermodynamically preferred exo isomer has also been reg ported for adducts of fulvenes . The question of mechanistic pathways for endo/exo isomerizations of Diels-Alder adducts has been examined in a variety of diene/dienophile systems, and several possible mechanisms have been proposed for observed endo to exo isomerizations. The first of these possibilities, and the one most universally applicable is a retro-DielsAlder reaction followed by subsequent recombination to form 9 the thermodynamically more stable product. However, in some systems intramolecular endo to exo isomerizations can 9 occur by a one bond cleavage-hydrogen shift mechanism. A third mechanism formulated by Berson et al., for the isomerization depicted above is a process involving dissociation of the endo adduct to the endo-addition complex, which through rotation isomerizes to the exo -addition complex, followed by rapid recombination to give a net "internal" isomerization. However, this mechanism has not been firmly established, and has been challenged by other authors. Also, Berson and his co-workers attempted to

PAGE 13

obtain evidence for their internal isomerization mechanism in two other systems , "^^ ' "^-^ '^'^ but the data obtained best support the retro-Diels-Alder-recyclization mechanism. Alkyland Aryl-Cyclopropenes as Dienophiles A special case of the Diels-Alder reaction involves utilization of cyclopropenes as dienophiles. Cyclopropene itself reacts at C with cyclopentadiene to form only endo-tricyclo[3.2.1.02,4]^^^_g_^^^_15 ^^^ corresponding exo -alkene had been prepared from bicycle [ 2 . 2 . l] hepta-2 , 6diene by Simmons and Smith using methylene iodide in the presence of zinc/copper couple. ""-^ Cyclopropene also reacts with 6 ,6-dimethylfulvene to form only an endo Diels-Alder 17 adduct, and this cycloaddition offers a convenient synthetic pathv/ay into the endo-tricyclo [ 3 , 2 . 1 . 0^ ' "^ ] octyl ring system. Subsequently, the reaction of 6 , 6-dimethyl(or 6 , 6-diphenyl) fulvene with 1 , 2 , 3-triphenylcyclopropene was reported by Martin to give a 1:1 adduct. However, careful "'"H nmr analysis indicated that the adduct had the exo structure. Cyclopentadiene also forms endo syn -3-methyltricyclo[3.2.1. 0^''^]oct-6-ene with 3-methylcyclopropene. "^'' ' ^"^ Semi21 larly, 1 , 2-diphenylcyclopropene , 1 , 2 , 3-triphenylcyclo21 91 propene, 1 , 2-dxphenylcyclopropene-3-carboxylic acid, and 1 ,2-diphenylcyclopropene-3-carboxylic acid methyl ester'^"'" all form endo 1:1 adducts with cyclopentadiene at room temperature . Curiously, 3 , 3-dimethylcyclopropene does not react with cyclopentadiene even at 100° C,^° presumably due

PAGE 14

to large steric interactions of the geminal methyl groups with the cyclopentadiene molecule in the transition state. It is evident that such interactions are sufficient to inhibit adduction in either the exo or the endo mode. If, however, forcing conditions are used, sterically inhibited reactions can be carried out, as in the case of the reaction of cyclopentadiene with 3-acetyl-3-methylcyclopropene ethyleneketal (1) at 140° C for 12 hours. ^^ The adduct so obtained was shown, by chemical conversion to a known compound, to have an exo structure. Even more anomalous was the behavior of the ketone, 3-acetyl-3-methylcyclopropene (2), which at 140 C apparently rearranges to l-methyl-3-acetylcyclopropene (3_) before adduction with cyclopentadiene to give endo-anti-2-methyl-3-acetyl-tricyclo[3. 2 . 1 . 0^ ' "^ ]oct-6ene, as shown below. CH 3 -CH. o A -> CH 3^CH3 CH. -CH, A 1 9 I A -> CH H 33 A -> jj. COCH^

PAGE 15

The use of dienes other than cyclopentadiene in DielsAlder reactions of cyclopropenes has produced some strikingly different results from the standpoint of the stereochemistry of [4 + 2] adducts. Indeed, the predominant stereochemistry of adducts produced in reactions of alkyland aryl-cyclopropenes with furan is exo . Cyclopropene reacts with furan to give a 1:1 mixture of exoand endo-8-exatricyclo [ 2 . 2 . 1 . 0^ ' '^ 22 23 oct-6-ene. ' When 1 , 3-diphenylisobenzof uran is the diene component, exo products are obtained with cyclopropene, 1methylcyclopropene, 1 , 2-diphenylcyclopropene, and 1,2,321 triphenylcyclopropene. After 3 days in refluxing xylene, tetraphenylcyclopropene and 1 , 3-diphenylisobenzof uran showed 21 no signs of reacting, but 3-methyl-l , 2 , 3-triphenylcyclopropene under the same conditions gave after 3 days 3-methyl1,2,3,4, 5-pentaphenyl[6,7] -benzo-8-oxatricyclo [3,2.1.0^'^]21 24 oct-6-ene ' (albeit in only 8% yield) . This behavior by a tetra-substituted cyclopropene is in sharp contrast to the findings using cyclopentadiene, which were discussed above. Clearly then, the steric and electronic factors controlling the stereochemistry of addition as well as the reactivity on Diels-Alder reactions of cyclopropenes vary considerably between cyclopentadiene and furan or 1 , 3-diphenylisobenzof uran. It is instructive to examine the evidence used by the various investigators to evoke either exo or endo stereochemistry for [4+2] cycloadducts of alkyland aryl-cyclopropenes. In some cases stereochemical assignments are based on comparisons to known compounds ' ' ' ^^^ ^^ others H

PAGE 16

nmr data are used to make the assignments . ^"'' ' ^^ ' ^"^ ' ^'* ' ^^ The adducts of cyclopentadiene with 1 , 2 , 3-triphenylcyclopropene and 1 , 2-diphenylcyclopropene-3-carboxylic acid were ascribed endo configurations based on the chemical shift of the lone cyclopropyl proton, which in either case appears at higher field than expected due to shielding by the C=C double bond. When both adducts v/ere reduced to the saturated compounds with diimide, the cyclopropyl proton signal is shifted downfield by approximately 0.5 ppm, as shov/n below. T 7.5 3 I[N^H^] ^ T 7.0 3 I CO^H T 7.7 2 H[N^H^: > T 7.27 H 1 8 An analagous argument was used by Martin to settle the question of stereochemistry in the 6 , 6-dimethylf ulvene adduct (_4) of 1 , 2 , 3-triphenylcyclopropene . Comparison of the chemical shift values of the cyclopropyl benzylic proton in this adduct with the same proton in the exo-anti-

PAGE 17

(5) and the endo anti (6) -2, 3 , 4-triphenyltricvclo [ 3. 2 . 1 . 0^'^]oct-6-enes pointed to the exo structure of the fulvene adduct, as shown below. H)63.27 3.75 22 2 3 Turning to the adducts of furan ' and 1 , 3-diphenyl24 25 1 isobenzofuran, ' H nmr prarmeters have once again been used to elucidate stereochemistry. The reaction of cyclopropene with furan produces a 1:1 mixture of the exo(7)and endo (8) adducts. In the exo case, no significant coupling is observed between the bridgehead protons IL and b the cyclopropyl methine protons H . However, in the endo adduct, the H nmr spectrum indicates substantial H, -H b X 24 coupling. The cyclopropene adduct (9_) and the 1 , 2-diphenyl5.95 4.55 ^bx-^ HZ 1.0 ;i.75 i4.77 J, 7^ Hz bx

PAGE 18

10 25 cyclopropene adduct (1_0) of 1 , 3-diphenylisobenzofuran were both assigned exo structures based on the observed chemical shifts of their cyclopropyl protons syn to the oxygen bridge in either case. This type of proton is subject to steric deshielding by the lone electron pairs on the oxygen. Shown below are the chemical shifts, multiplicities, and observed coupling constants for 9 and 10. (mult) J (Hz) H 1.84 J = 5.2 a /^ -c .\ ab (d of t) H, 0.84 b J = 3.7 ax H 1.62 (d of d) J, = 6.74 X ' bx 10 (mult) J (Hz) H 2.94 (d] a H^ 1.8 b Id) J , = 4.7 ab Thus, it would seem that by careful consideration of H nmr data obtained for Diels-Alder adducts of alkyland aryl-cyclopropenes, it is possible to make definitive exo of endo structural assignments with a reasonable degree of certainty.

PAGE 19

11 The task of rationalizing why these cycloadditions of furan and 1 , 3-diphenylisobenzof uran give exo products in variance to the Alder rule is no less difficult than ascertaining the correct stereochemistry of the adducts. 22 LaRochelle and Trost advanced such an explanation based on the transition state structures for exo and endo adduction. They envisaged an exo transition state as being distinctly like a boat cyclohexane (as shown below) , and thus subject to destabilization by 1,3 "flagpole" interactions, which could be substantial in those cases where the diene is cyclopentadiene. When the -CH of cyclopentadiene is replaced by -0(furan or 1 , 3-diphenylisobenzofuran) , the 1,4 steric interactions in the exo transition state are evidently reduced enough to enable the reaction to proceed to give exo products. However, it must VS be pointed out that although this transition state argument seems to adequately explain the results of the Diels-Alder reactions of alkyland aryl-cyclopropenes , it obviously does not take into consideration electronic factors and other steric interactions in the transition state which may

PAGE 20

12 also be substantial enough to affect the exo/endo ratio of products. Halocyclopropenes as Dienophiles Armed with the knowledge that alkyland aryl-cyclopropenes undergo Diels-Alder reactions with acyclic and cyclic 1,3-dienes, several authors undertook investigations directed towards the synthesis of and Diels-Alder reactions of halogenated cyclopropenes . Since 1963, several thermally stable halogenated cyclopropenes have been synthesized. In that year, Tobey and West reported the dehydrohalogenation of pentachlorocyclopropane in 18M aqueous KOH to give tetrachlorocyclopropene (1_1) , ' which these same authors subsequently employed as the starting material for tetrabromocyclopropene (12_) , 3-f luoro-1 , 2 , 3-trichlorocyclopropene (13), 1, 2-dichloro-3, 3-difluorocyclopropene (14_) , and 1,2-dibromo2 8 3, 3-difluorocyclopropene (15^). Reduction of 1]^ with tri2 Q n-butyltin hydride as reported by Breslow et al. affords a mixture of 3-chlorocyclopropene (59%), 3 , 3-dichlorocyclopropene (14%), and 1 , 3-dichlorocyclopropene (27%). In 1969, CI CI CI ^ CI fcl CI CI H 11 Sargeant and Krespan reported the successful synthesis of 30 perf luorocyclopropene (1^) , as well as the duplication of

PAGE 21

13 the synthesis previously reported of 1, 2-bis (trif luoro31 32 methyl) -3, 3-difluorocyclopropene (17_) . ' Other reported gem -dif luorocyclopropenes include some 1(perf luoroalkyl) 33 3, 3-dif luorocyclopropenes and some steroid derivatives incorporating a gem -dif luorocyclopropene moiety. Since many of the cyclopropenes mentioned above are thermally stable and relatively high boiling, several authors have taken advantage of these properties to prepare [4+2] cycloadducts with a variety of cyclic and acyclic dienes. Since the structural assignments of these adducts rests on conclusions drawn from spectral data, these data will be closely examined. Also, due to the subtle differences observed in the spectra for pairs of stereoisomers, such differences will be discussed in terms of their relevance to making structural assignments. The most widely reported perhalocyclopropene to be used as a dienophile is tetrachlorocyclopropene (1_1) , which forms 1:1 adducts with furan, ' 13 , 14-dioxatricyclo[8.2.1.1'^' ]tetradec-4,6,10,12-tetraene,^'^, 1 , 3-diphenylisoK ^ 24,38 , ^ ^. 35 , , , . . . benzofuran, cyclopentadxene , and the acyclic dienes 35 39 1, 3-butadiene, and trans , trans -1 , 4-diphenyl-l , 3-butadiene. The observed ring opened product of lA with furan was envisaged by Law and Tobey to arise through an initially formed endo tricyclic adduct, which at the reaction temperature (80 -C) undergoes facile ring opening to 2 , 3 , 4 , 4-tetrachloro8-oxabicyclo [ 3 . 2 . 1 ]-octa-2 , 6-diene. Completely analagous behavior was observed for tetrabromocyclopropene (12), as

PAGE 22

14 shown below. These authors based their conclusion that the CCl n X = CI 12 X = Br 80°C ^ initially formed [4+2] adduct was endo on transition state calculations carried out by Herndon and Hall on the cyclopentadiene dimerization, and transition state steric arguments for the system shown above. An interesting alternative mechanism for the above reaction was considered by Magid and Wilson, which involved ionization of a labile methylene CI in ]^ to form the trichlorocyclopropenium cation, v/hich subsequently formed an ionic cycloadduct with furan, followed by rapid ring opening and capture by Cl~ to yield the observed product. However, their kinetic data obtained from the reaction using cyclopentadiene as the diene instead of furan, as well as stereochemical studies, precluded adoption of this ionic mechanism in that the data were more consistent with the direct cycloaddition mechanism. A contrasting opinion of the stereochemical mode of tetrachlorocyclopropene [lA) cycloadditions was advanced in 37 1971 by Battiste et al., who suggested that the initial reaction of ]J^ with the [2,2] (2 , 5) -furanophane shown below occurs to give the exo adduct, which undergoes further

PAGE 23

15 reactions. These authors cited the analagous reactions of 11 + o o on furan and 1 , 3-diphenylisobenzof uran discussed above ' as the basis for their supposition. Since it is impossible to obtain absolutely reliable stereochemical information from spectroscopy alone for adducts of tetrachlorocyclopropene (11) / other means must be sought for accurate structure determinations. In this vein, Bordner and Hov/ard, in collaboration with Magid and Wilson, have recently conducted a single crystal X-ray analysis of the adduct of 11 with 1, 3-diphenylisobenzofuran, which revealed that the adduct is unquestionably exo, thus lending support to the contention that perhalocyclopropene Diels-Alder reactions may in fact proceed in the exo , or "anti-Alder" manner. When one or both of the geminal positions of a perhalocyclopropene are substituted with fluorine, the monoor gem -di-f luorocyclopropenes , when reacted with a diene, form the corresponding fluorinated cyclopropanes , which in many cases are stable to ring opening at the reaction temperature due to the inherent strength of the C-F bond. The fluorinated cyclopropenes that have been studied as dienophiles have been

PAGE 24

16 synthesized principally by Tobey et al , , ' and Sargeant. ' Tetrachlorocyclopropene (1]^) , when treated with SbF^, forms a separable mixture of 1 , 2 , 3-trichloro3-f luorocyclopropene (1^) and 1 , 2-dichloro-3 , 3-dif luorocyclopropene (1_4) . Tetrabromocyclopropene (12_) , when subjected to treatment with SbF at somewhat higher temperatures forms a single product, 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15^) , Diels-Alder adducts with furan for all CI CI CI 13 CI CI 14 ^ 126.7) (138.4: H, (5.30) b 19 15 -> Br

PAGE 25

17 three of these f luorocyclopropenes were first prepared in 35 1968 by Law and Tobey and were assigned the structures shown above. The H nmr chemical shifts are in 6 relative 19 to TMS, and the F nmr chemical shifts are in 6 upfield from CFCl^. All shift values shown are as reported by Law and Tobey, and the assignments are their own. Close inspection of the nmr data for the tricyclic compounds 1^, 19_, and 2_0 reveals some interesting features. First, a fluorine cis to either Br or CI has a signal at lower field than a trans fluorine. Note that in the monofluorinated compound (1_8) , the single ^F resonance may be assigned with reasonable certainty to a fluorine trans to the two bridgehead CI atoms. Also, the 6 values indicate more efficient deshielding by a cis Br than a cis CI, as expected. Second, in both of the gem -difluoro compounds, (19) and (2_0) , only one fluorine, the fluorine trans to either Br or CI and at highest field, is coupled to H (J = 2 Hz) . The single fluorine resonance of the monofluoro compound (1^) also appears as a triplet (J = 2.5 Hz), thus supporting the other assignments. Tobey and Law in 1968, with Magid and Wilson concurring in 1971, therefore assigned the endo structures to 18_, 19_, and 2_0 as shown above. However, if all three structures are considered to be exo, the H,. F(136.5) (92.0) Hj^(5.29) H^(6.81) "20a'

PAGE 26

nmr data can be made to "fit" equally well, as shown above taking 2_0 as an example. In accordance with the criteria established above, in the now exo 20a , the lowest field fluorine is cis to the two Br atoms, and the higher field fluorine is coupled to H and appears as a doublet of triplets (Jpp = 144 Hz, J^^ = 2 Hz). Tobey and Law argued b that in 2_0, the high field fluorine is shielded by the C=C double bond since this adduct was thought to be endo . This argument is not justified, since the same shielding argunts that are well established for H nmr cannot be applied me 19„ 41 , . . to F nmr. This is particularly so in the compounds in question, due to the lack of data for suitable model compounds. Two other furan adducts of gem -dif luorocyclopro3 1 penes have been reported by Sargeant. Tetraf luorocyclopropene (1_6) and 1,2 bis (trif luoromethyl) 3, 3-dif luorocyclopropene (1/7) form 1:1 furan adducts, 2A and 2^, respectively, at room temperature, both of which are shown in Table I with the structural and nmr spectral assignments as made by Sargeant. Table I 1 19 H and F nmr Data for 2J^ and 22 6ppm mult. splittings, Hz assign. J, Hz 6H 6.32 M W, ~4 c,d FF = i^ a b 4.60 2 X M 3.4, W^ ~ 8 a,b 175 6F F^F b c „, 129.9 2 0.3 F^ 0.0 21 b 139.3 3X323.3,3.2 F 23.4 3. 227.8 2 23.4 F H ^F =3.2 c a ,b a

PAGE 27

19 22 Table I Continued 6ppm mult. splittings, Hz assign. J, Hz 6H 6.62 1 5.17 1 6F W^/2-3.8

PAGE 28

20 1 19 withm the H and F nmr data require that the alternate exo structure 21a be considered. To this end, 21a, the revised exo structure, accompanied by the reassignments 1 19 for the H and F nmr spectra, are illustrated in Table II. Even though this structure eliminates the problem of Table II 1 19 H and F nmr Data for 21a 21a b c,d a,b ^Ppn^ mult. splittings, Hz assign. J, Hz 6H 6.32 M 4. 60 2 X M 3.4, W, ~ b 6F 129. 9 2 0.3 139.3 3X3 23.3, 3.2 227.8 2 23.4 F F, = a b 175 F, F = b c 0.0 F F = a c 23.4 F H , ( ? ) a a,b 3.2 no observed J^^ ^ (since bridgehead-H/ endo -H coupling a,b c ^2 is usually negligible) , the chemical shift values as assigned here do not agree with the previously observed"^^ appearance of the geminal fluorine cis to C21C cyclopropyl halogens at lower field than the trans geminal fluorine. Thus, it would seem that in the absence of other data to resolve the paradox, such as heteronuclear decoupling results, the assertion by Sargeant that "the stereochemistry [of 2_1] cannot be assigned with certainty" must remain unchanged.

PAGE 29

21 Re-evaluation of the structure of the l,2-bis(trifluoromethyl) -3,3-difluorocyclopropene adduct 2_2 in the same fashion (that is, as the exo adduct 22a ) , may prove more productive than in the case of 2]^. Once again, 1 19 fitting the observed H and F nmr data to 22a, one obtains the results shown in Table III. Of interest here Table III 1 19 H and F nmr Data for 22a >PPn^ mult. splittings, Hz assign. J, Hz 22a 6H

PAGE 30

22 Thus, if the structure of one of these furan Diels-Alder adducts could be established concretely, the development of diagnostic techniques applicable to other compounds of this type might be in the offing. The problem of correctly assigning stereochemistry in halocyclopropene adducts is further confounded by the existence of a body of data for cyclopentadiene adducts of other halocyclopropenes . One such study by Magid and Wilson dealt with cyclopentadiene adducts formed by reaction of excess cyclopentadiene with a mixture of 3chlorocyclopropene, 3 , 3-dichlorocyclopropene, and 1,3dichlorocyclopropene. ' Curiously, these authors did not report formation of an adduct from the 3 , 3-dichlorocyclopropene. However, the remaining cyclopropenes afford 1:1 adducts ^ and 2_4, both of which appear to be exclusively endo, as shown below with the appropriate H nmr data. Other evidence for structures 23 and 24 was obtained from the H61.7 H61.81 1.5Hz) i6.01 2.5Hz 23 24 reaction of norbornadiene with chlorocarbenoid, which yielded

PAGE 31

the monochloro fpdx)-anti compound 2_3 as well as the exoanti isomer 2_5 shown below with its H nmr data. (That CH2CI2 CH^Li -> 23 + 10.8 61.1 25 H63.68 (J = 1.5Hz : 23 26% 74% carbene additions to bicyclic systems such as norbornadiene proceed to give preferentially exo addition products has 43 44 been well documented, ' and will be discussed later.) Finally, reduction of 23 by sodium in tert-butyl alcohol produced only the known endo-tricyclo [ 3 . 2 . 1 . 0^ ' '^ ]oct-6-ene. Other than the ring opened adducts of tetrabromocyclopropene (12^) and tetrachlorocyclopropene (11_) prepared by 35 Law and Tobey, only tv;o other halogenated cyclopropenes have been treated with cyclopentadiene, namely l,2-bis(trifluoromethyl)-3,3-difluorocyclopropene (1_7) and tetra3 1 fluorocyclopropene (1^) , as reported by Sargeant. Cyclopentadiene when reacted at room temperature for 24 hours with 1^ gave only 2 , 3 , 3 , 4-tetraf luorotricyclo [ 3 . 2 . 1 . 0^ ' "^ ] oct-6-ene (2_6) , but the bis (trif luoromethyl) compound 11_ gave two products, 21_ and 28^, in 90% yield in a 69:31 ratio. Once again/ all three of these compounds with the nmr data

PAGE 32

24 as reported and assigned by Sargeant are shown in Table IV. Table IV 1 19 H and F nrar Data for 26, 27, and 2!

PAGE 33

25 Table IV Continued 5ppm mult. splittings, Hz assign. J, Hz •SH H H.=8,4 e f c,d CF^F =19.0 3 a 3.57 1 W^^2~6.5 a,b CF^F =2.6 2.36 1 W, /^ ~ 5 e F F^=177 1/2 a b 1.84 1 W, /„ ~ 7 f H^F =8.5 28_ ^/^ ? a 6F 61.7 2X2 19.0, 2.6 CF 109.4 7 X 2 19.0, 8.5 F a 136.0 7 2.6 F, b The assignments of stereochemistry in 21_ and 28 as well as some of the nmr chemical shift assignments are somewhat suspect, and it becomes necessary at this point to indicate several anomalies in Sargeant's proposed structures. First, on chemical grounds, one would expect both tetrafluorocyclopropene (16^) as well as 1,2-bis(trif luoromethyl)-3, 3-difluorocyclopropene (17_) , when reacted with cyclopentadiene, to imitate the propensity of other cyclopropenes towards preferential, if not exclusive, endo addition. / ^ » however, Sargeant proposed the exo compound 2_8 as the major reaction product. Also, cyclopentadiene adducts of this general type are believed as a rule to be more thermodynamically stable when 1 45 in the exo form, ' in spite of any steric interaction

PAGE 34

26 between a syn bridge hydrogen and a cyclopropyl methylene substituent. Thus, the isomerization of 2_8 to 27 envisaged by Sargeant would not be anticipated based on the relative thermodynamic stabilities of the two isomers. In addition, the assertion by Sargeant that exo 28 isomerizes to endo 27 , which further rearranges to the tetracyclic system 2_9 as shov^?n below seems curious in that conversions of the type that give tetracyclic products such as 2_9 are believed to take place from the exo stereoisomer. 28 27 200°C CF CF. Further examination of the nmr data for 22 and 28 also suggests that their structural assignments are reversed. 46 1 Recent analysis of the H nmr spectrum of endo -1, 5,6,72 4 tetrachlorotricyclo[3.2.1. ' ]oct-6-ene (30) has shown that substantial long range coupling amount to 2.5 Hz exists between the anti bridge proton H^ and the outside cyclopropyl

PAGE 35

27 methylene proton H^. Since H "^^F long range couplings are usually. larger in magnitude than the corresponding H H couplings, the H and F spectra of the adduct thought by Sargeant to be endo ( 27 ) should contain evidence 19 1 of long range F H coupling from anti proton H to the outside fluorine F^. According to the assignments made by Sargeant, though, F^ appears as a clean septet coupled only to the CF^ groups (J = 19.0 Hz). There is also an unassigned coupling to F of 2,8 Hz. However, in 3_0, J is only 0.30 Hz, so that the coupling F H could possibly be 2.8 Hz, but no data pertinent to this question are available at the present time. Turning to 2_8, claimed to be exo by Sargeant, there is a large coupling to F^ ( cis to the CF groups), amounting to 8.5 Hz, which Sargeant left unassigned. Noteworthy also is that of the two bridge protons H and H^, only H , at 61.84, has a W^^ ^2 (~'7 ^z) sufficient to possibly accommodate an 8.5 Hz long range fluorine coupling. In view of the contradictions manifested by 2_7 and 2_8 in their chemical behavior as well as the anomalies present in their nm.r spectra, it is instructive to reverse their stereochemical assignments. That is, assuming 2_7 to be exo (27a) and 28 to be endo ( 28a ) , it is possible to analyze and assign the observed nmr data more satisfactori. ly . The revised exo/ endo assignments are presented in Table V with the appropriate nmr data. Examination of the revised assignments in Table V leads to a more satisfying fit with empirically determined

PAGE 36

28 Table V 1 19 H and F nmr Data for 27a and 28a oppm mult. splittings, Hz assign. J, Hz 6h 3 2.01 1 27a V2~^-^ V2 ~ ' W 1/2 1.15 1 6f 59.9 2X2 19.0, 2.6 113.7 7 19. 129.9 2X7 2.8,2.6 c,d a,b f CF. H H^=8.6 e f F CF^=19.0 a 3 F, CF= 2.6 b 3 F F^=178 a b F, H_ = 2.8 b ? 28a 6H 6.27 2X3 3.0 3.57 1 2. 36 1 184 1 OF 61.7 2X2 19.0,2.6 109.4 7X2 19. 0, 8. 5 136.0 7 2.6

PAGE 37

29 trends in the nmr spectra of tricyclic compounds of this type. First, the appearance of H at higher field than H^ is consistent with shielding of H by the exo cyclopropane ring. Note that 6H in endo 28a is greater than 6h^ in 27a , supporting this mode of shielding for the exo compound. Second, a tentative assignment of J 19 1 b ^'^ m 27a can be made, since 4-bond F H coupling of the order of 2.8 Hz is not unusual. ' Lastly, the most telling argument for the structural assignments above is the assignment of the large (8.5 Hz) long range F H coupling of F^ to H^, which in 28a should be much larger 19 1 than any long range F H coupling in 27a . If 27a and 28a are indeed the correct structures for Sargeant's adducts, the isomerization data he reported adhere more closely to the known thermal behavior ob1 4 8 served in other exo and endo tricyclic compounds. ' In addition to the fact that the preferred endo adduct 28a now becomes the major reaction product, the isomerization at room temperature of the less stable 28a to the more 1 4 8 stable exo isomer ( 27a ) now parallels existing data. ' Also, the quadricyclic product 29^ as depicted below is now seen as arising from 27a upon heating at 200° C instead of from 28a , again in conjuction with previous data. ' ' To conclude, then, that 27a and 28a are the correct structures for the Diels-Alder adducts synthesized by Sargeant seems quite reasonable, in terms of both their chemical behavior as well as the nmr spectral data reported.

PAGE 38

30 R.T, CF. CF. 17 200°C V CFCF. 29 49 Recent work by Jefford et al. involving dif luorocarbene addition reactions (which will be discussed later) has, in fact, given strong indications that our reassessments of the structures of 27 and 28_ and their spectra are most probably correct. Unfortunately, there are several inconsistencies in 31 the data reported for the cyclopentadiene adduct 2 6 of perf luorocyclopropene (16) , which make the unambiguous assignment of stereochemistry impossible. For example, F appears at higher field than F^^, in contrast to previously 35 reported data for other gem -dif luorocyclopropene adducts. Also, a coupling of 2.3 Hz is assigned to J , whereas c a, b this type of coupling should probably be on the order of 3.5 4.0 HZ. 20' 21, 42, 43

PAGE 39

31 Objectives of This Work Given the number of Diels-Alder adducts of perhalocyclopropenes that have been prepared and the paucity of definitive structural information about these compounds, there was an obvious need for reinvestigation of many of the reactions in question with an eye towards establishing reliable criteria for making structural assignments in these systems, as well as correcting any erroneous structural assignments. To develop the synthetic potential^^ of cyclopropene Diels-Alder reactions to the utmost, those who utilize these cycloadditions must have at their disposal the means by which exo / endo assignments can be made with certainty. Several methods by which such assignments may be made lend themselves to the work in question. The most likely methods to be used are the spectroscopic techniques, 19 1 especially F and H nmr. But for these to acquire the reliability sought, a great many more data must be compiled for a variety of structural types. However, the method that is possibly the most unassailable, and a technique which is coming more and more into prominence in organic structural studies, is single crystal X-ray analysis. This method has the advantage of requiring a minimal amount of material, and since the output is usually in the form of computer drawn structures, relatively subtle differences in bonding or stereochemistry, which might be undetectable otherwise, can be clearly ascertained. Our objective was to establish the structure of one of

PAGE 40

32 the previously reported fluorinated cyclopropene adducts by X-ray crystallography, and then using the "^H and "'"^F nmr parameters for this "known" system, to develop nmr spectral criteria for making structural assignments in related systems. Included in this endeavor was the synthesis not only of the cyclopropenes and the Diels-Alder adducts thereof, but chemical conversions of most of these adducts to new compounds so that the methodology used might be expanded to include more structural types. Specifically, these transformations consisted of reducing the C=C double bonds in some adducts and/or treatment of these vic-dihalogem-difluorocyclopropanes with tri -n-butyltin hydride to obtain the corresponding gem -dif luorocyclopropanes . The characterization of these compounds was expedited by the distinctive H and F nmr spectra of the general structure shown below. (n-Bu) 3SnH -> \ F H X = CI, Br It is interesting to note that the synthetic step depicted above is equivalent with res.pect to the overall structures involved to (i) performing the original DielsAlder reaction using 3 , 3-dif luorocyclopropene as the dienophile, or (ii) addition of the dif luorocarbene (:CF^) moiety

PAGE 41

33 to a cyclic or bicyclic olefin. What may not be as analogous is the stereochemistry of the products so obtained. For example, while some of the [4+2] cycloadditions might yield endo products, their exo analogs should be obtainable via the dif luorocarbene sequence. The discussion of the details of our synthetic investigations of 3 , 3-dif luorocyclopropene as well as discussion of dif luorocarbene additions will be deferred until the appropriate time in Chapter II, in order to avoid redundancy,

PAGE 42

CHAPTER II RESULTS AND DISCUSSION Stereochemical Studies of Perhalocyclopropene [4+2] Cycloadducts " As discussed earlier, in light of the imprecise nature of assigning stereochemistry to Diels-Alder adducts of perhalocyclopropenes, it was our belief that a means should be found to unambiguously assign an exo or endo structure to one such compound, and then apply the spectral parameters observed for that compound to other similar adducts of unproven structure. We selected as our model system 2,4dibromo-3,3-difluoro-8-oxatricyclo[3.2.1.0^''^]oct-6-ene (20) , first prepared by Law and Tobey in 1968^5 f^Q^i 1,2-dibromo3,3-difluorocyclopropene (1_5) and furan, and assigned the ^"do structure shown. This compound is one of the "stable" Br \ Br 15 CCl 80°C ^ adducts of this general type that have been prepared, meaning that 2_0 appears to be thermally stable to ring opening 34

PAGE 43

35 reactions at 100 C, the pot temperature used by Lav; and Tobey in their distillation of 2^. As elaborated earlier, nmr spectroscopy did not provide a suitable proof for the stereochemistry of 20^. To this end, it was deemed essential that a single crystal X-ray analysis should be carried out on the same material that was reported by Lav; and Tobey. Synthesis of 20_ naturally required 1_5 as a precursor, and the reaction sequence developed by Tobey and West^^ ' ^"^ ' ^* was repeated, as shown in Scheme I (for specifics concerning yields, etc., see Experimental). The Diels-Alder reaction Scheme I CI CI 11 12 BBr. ^ SbF. A -> -> Cl2C=CHCl + Na"^ O^CCCl CI Cl^ CI "\ glyme Cl CI 11 12 15 Cl Cl-/ Cl ^ ClCl was carried out as described by Law and Tobey. Instead of using only a short path distillation, however, our crude reaction mixture was passed through florex with pentane.

PAGE 44

36 the solvent was removed, and the residue was sublimed to give a material which had all spectral properties identical to the literature report. "^^ Oddly, the melting point of the sublimed adduct was 36° lower than the literature value, so that the state of purity of the material from our sublimation required closer examination. Analysis by gas chromatography as well as reexamination of the ^^F nmr spectrum of this material indicated that only one adduct was present, and that it was indeed identical to the compound reported as 20. Having established the authenticity of our furan adduct, the next step in the structural determination was the reaction of 2_0 ( 20a ) with phenyl azide (31) to form a 1:1 adduct, 3_2. There were two major reasons for preparing 32. 20 ^ 32 First, 20^ ( 20a ) proved to be far too volatile at room temperature to permit analysis by X-ray diffraction, and second, although _20_ ( 20a ) was a solid, 32_ formed crystals that were more amenable to the shaping and mounting procedures required for single crystal X-ray studies (see Experimental) . The results of the X-ray structural determination are shown in

PAGE 45

37 4-1 o 0) H > QJ M 0)

PAGE 46

38 Figure 1, which is a stereoview of the complete structure 51 of 32_. As anticipated, the phenyl azide moiety added to 2_0 ( 20a ) in a 1,3-dipolar fashion, resulting in the formation of the exo 5-membered ring. Of paramount importance, however, as Figure 1 unmistakably shows, the gem-difluorocyclopropane ring also has the exo stereochemistry. One consequence of this finding is that the structure of the original Diels-Alder adduct (from which 32 was synthesized) had to be 20a, the exo structure discussed earlier, and not 20 , the endo isomer originally proposed by Law and Tobey. The immediate impact of this single result was that the stereochemistries assigned to the other furan adducts prepared by Law and Tobey as well as those prepared by Sargeant , ^"'" required reevaluation. Using 20a , now known to be exo , as starting material, three other compounds were synthesized from it that retained the gem -difluorocyclopropane ring. These chemical transformations are shown in Scheme II. It should be noted that Scheme II (n-Bu) ^SnH (t-BuO; A ->

PAGE 47

39 of the reactions used in Scheme II, none are currently suspected of causing exo to endo isomerizations , either by a retro-Diels-Alder type mechanism, or by inversions at individual carbon centers. In support of our contention that all of the compounds in Scheme II have the exo structures shown, is the -""^F chemical shift of F, , which for the brominated compounds 20a and 33_ has values of 136.5 ppm and 135.5 ppm, respectively (also, as further proof, in the phenyl azide adduct 32^, 6F, is 134.2 ppm), indicating that F^ in each case resides in approximately the same environment. When the bridgehead Br atoms are reduced to hydrogen atoms, as in 3_^, 35_, and 3_6, F, now appears at 145.9 ppm, 143.4 ppm, and 144.9 ppm, respectively, again indicative of equivalent environments in these compounds, as well (for complete -""H and ""-^F nmr data, see Table IX, p 87 ) . Of course, correct assignments of F^ T • 19 and Fj3 are crucial if the observed trends in F nmr chemical shift values are to be of any use. In 34, 35, and 36_ (and hence in their precursors in Scheme II) this task is made trivial by observation in the "'"^F spectra of the large (12-13 Hz) triplet coupling of F to the cyclopropyl protons. This cis vicinal "'"^F -""H coupling is much larger 19 1 than the trans vicinal F H coupling, which is 1,5 2.5 Hz. Therefore, in principle, if a gem -dif luoro-1 , 2-dihalocyclopropane can be successfully reduced in the manner shown above, F nmr assignments should be rather straightforward. In conjunction with the above technique, correct assignment of stereochemistry in analagous compounds can now be

PAGE 48

40 made by conversion of one of the compounds of known stereochemistry to a compound which can also be derived from an adduct of unknown structure. In lieu of this direct method, since such conversions are not always possible, we have made use of three other spectroscopic techniques for determination of stereochemistry. The first of these techniques involves measurements in H nmr spectra of line widths at half height (^^^2^' which gives a measure of the maximum value that can be attributed to all couplings to the particular nucleus under scrutiny. For example, in the H nmr spectrum of 35_, W .^ for the cyclopropyl protons (H-, ) is 0.75 Hz, indicating that J must be no greater than 12 this ceiling value. If 35 were endo, J„ „ , and hence W-, ,^ for H-j^ would be expected to be much larger, as discussed 41 42 previously. ' Measurements of W ,„ will henceforth be quoted when they are relevant to structural assignments. Secondly, and as a further refinement of the W , technique, we employed heteronuclear decoupling to provide another means of estimating coupling constants such as J . In a typical 19 12 experiment, each F nucleus was irradiated in turn and the resulting H nmr spectrum was recorded. Also, due to the 1 19 A6 between H and F nuclei, both F and F, could be simula b taneously irradiated, giving a fully decoupled H nmr spectrum, This method, therefore, provided a way of obtaining W-, ,^ data 19 from F decoupled spectra, which, when considered with the undecoupled spectra, usually allowed for more certain exo /endo assignments. Heteronuclear decoupling proved to be quite

PAGE 49

41 useful for furan adduct assignments as well as for adducts of some cyclopentadienes , which will be discussed later. Finally, in those cases where an oxygen atom formed a bridge in an adduct (of furan and related dienes), we had hoped that the use of Eu(FOD) as a shift reagent might give rise to a correlation between stereochemistry and the observed rate of shift for the H resonances. The results we obtained using 34_ as a reference compound will be discussed, at the appropriate time, and although they were not as quantitative as we had hoped, some interesting trends were observed from which tentative inferences regarding the nature of Eu(FOD)-, complexation can be drawn. 35 Since 20a , as prepared by Tobey and Law, had the exo structure as shown by X-ray analysis, the prospect of detecting additional incorrect assignments became much more likely. These suspicions were well founded, since the furan adduct (19^) of 1, 2-dichloro-3 , 3-dif luorocyclopropene (14) , considered to be the endo isomer by Tobey and Law, also proved to have exo stereochemistry. Our proof of structure consisted of duplicating the original synthesis of "19", followed by saturation of the double bond to give 3^ ^""^ reduction of the methine CI atoms, as shown in Scheme III. The resulting saturated, dechlorinated material had an infrared spectrum identical to the infrared spectrum previously recorded for 34^, prepared from authentic exo 20a. In retrospect, since the chemical shifts of F in 20a , 19a , 19 and the lone F in 18 (see Table I) fall within 2.0 ppm of

PAGE 50

42 Na,THF t-BuOH -> 34 20a -> A each other, the preliminary conclusion that all three of these fluorocyclopropene adducts are exo has now been firmly established for 20a and 19a , and a strong case can now be made for exo stereochemistry of the monof luorocompound 18 (as 18a ) as well. Noteworthy also, is the similarity of Fj^ (136.5) Fj^ (136.7) b 2 Fj^ (138.4) Vh=2.5 b 2 20a 19a 18a Jp ^ in all three compounds, which also points up the b 2 resemblance in the structural environments for F, in 18a, b — — 19a, and 20a. Bearing in mind the values for 6F, cited above, the previous discussion of the furan adducts 2^ and 2_2, reported 31 by Sargeant to be endo, becomes more germane. If these

PAGE 51

compounds are now taken to be exo , as mentioned previously, the correlation between 6Fj^, J^ ^ , and exo stereochemistry b 2 can be extended to 22a . The case of 21a has not yet been 43 Fj^ (139.3) tF^ J^ „ =1.2 CF3 22a resolved, since Sargeant quoted no values for J or J b 2 ^c 2 and there is still his reported J^ ,, = 3.2 Hz to be conr n „ a 2 sidered in terms of making a satisfactory structural assignment. Thus, no definite choice between endo 21 and exo 21a can be made at this point. Thus, having made the necessary corrections to the structures erroneously designated as endo [4+2] adducts of furan and some fluorinated cyclopropenes , attention was turned to the synthesis of new perhalocyclopropene-furan adducts, and then using the criteria discussed in relation to 20a , to extend the number of unambiguous structural assignments in this system. For several reasons, 1 , 2-bromo-3 , 3difluorocyclopropene (15^) was the dienophile of choice, even though its preparation involved four steps (see Scheme I) with an average overall yield of about 3%. First, 15^ was used in the initial work in the X-ray analysis, and to change the nature of the dienophile in use would have added another

PAGE 52

44 variable to a mechanistic scheme already laced with uncertainties. Second, from a more practical standpoint, of the gem -difluorocyclopropenes previously discussed, 15 had the advantages of being thermally stable, non-volatile, and most important, of possessing moderate relative re35 activity towards dienes. A choice of some other gemdifluorocyclopropene would have meant compromising some or all of the advantages of 15. The first diene we chose to react with 15 was 1,3diphenylisobenzofuran, which is also thermally stable yet fairly reactive towards dienophiles, due to the incipient aromaticity of the benzomoiety in the transition state for adduction. When this reaction was carried out at 80° C for 12 hours, the product consisted of 89.9% exo-2 , 4-dibromo3, 3-dif luoro-l,5-diphenyl[6, 7 ] benzo-8-oxatricyclo [ 3.2.1.0^''^]' oct-6-ene ( 38a ) contaminated with 10.1% of the endo isomer 38 . These assignments can be advanced on the basis of the 3 p X-ray study done by Bordner and Howard which proved that tetrachlorocyclopropene (11_) also gives an exo adduct with 1, 3-diphenylisobenzofuran. Also, on chemical grounds, the product predicted to be the most stable isomer would be exo ( 38a ) , and thus at 80 C should also be the major product. The evidence to support the endo structure 38_ consists of 1 19 the lack of signals in the H and F nmr spectra which could correspond to another type of structural isomer. That 38 is a structural isomer of 38a was borne out by the fact that the mixture gave a correct elemental analysis for the form.ula of

PAGE 53

45 19 38a /38. Also, the F nmr spectrum of 3_8 was completely analagous to that of 38a , consisting of a doublet of doublets with J^ ^ = 144.0 Hz. The intriguing question a b of exo / endo isomerism will be discussed later in relation to the 20/ 20a system, which was studied more extensively. Also, when 38a ( + 38_) was treated with tri -n-butyltin hydride at 100 C, only one product was formed, and was 19 assigned the exo structure 39 shown below. The F nmr ^ 93.3 [92.6] Fj^ 129.5 [136.2] 142.6 143.4] chemical shift data for 38a and 3_9, as compared to the analagous data for 20a and 3_5 (from the furan series, see Scheme II), shown in brackets above, speak favorably for both 38a and 3_9 to be exo . Law and Tobey "^ observed considerable internal consistency in their data, and used this as an argument for like stereochemistries in their compounds Even though their assignments appear to be reversed, the 19 trends in the data are still useful. Similarity of F nmr chemical shifts can be quite valuable in settling questions of stereochemistry, but in order to be of any value, the

PAGE 54

46 . . 19 individual F resonances must be assigned to the proper 19 F atoms in the proposed structure. Therein lies another advantage of converting the methine cyclopropyl Br atoms in adducts such as 20a or 38a to hydrogen atoms as in their reduced counterparts 35. and 3_9Assignment of the "'"^F cisvicinal coupling constant to these protons is simply a 19 matter of finding the F resonance with a large (10 15 19 Hz) Jp^ cis vic . The F trans vicinal coupling is small (1 2 Hz) but also measurable in the F nmr spectrum. This general method of confirming F nmr assignments was used throughout this work, and as a result, the F nmr assignments in Table IX should be accurate. If the phenyl groups in 3_9 were replaced by hydrogens the resulting compound would provide an opportunity for measuring coupling between the bridgehead protons and the methine cyclopropyl protons, which would be useful in making stereochemical assignments. This system would have a simple H nmr spectrum, showing only three well separated signals, and thus would also lend itself to facile W, ,^ measurements 19 m both the normal spectrum and the F decoupled spectrum. Of course, this hypothetical system corresponds to the [4+2] cycloadduct of 15_ with the parent isobenzof uran. The method of choice for generating isobenzof uran in_ situ and the one 5 2 that we employed in our reaction with 15 was that of Warrener, as shown in Scheme IV. The [4 + 2] adduct 40^ was immediately 19 suspected of being exo on the basis of the F nmr chemical shifts when they were compared to other "known" compounds, as

PAGE 55

Scheme I^' 47 + 15 CH2CI2 -> 0°C -> 40 discussed previously. Once again, reduction of 40 to 41 with tri -n-butyltin hydride allowed confirmation of the 19 F nmr assignments and thus lent support to the exo structures shown for A0_ and 41 . Additional evidence for structure 4_1 was obtained from its H nmr spectrum, which consisted of an aromatic AA'BB' multiplet, a doublet for the bridgehead protons (H^), and a doublet of doublets for the methine cyclopropyl protons (H-, ) . Since the signals for H„ and H, were widely separated.

PAGE 56

48 ^1/2 ^°^" them was easily obtained. In the undecoupled spectrum of 41_ W^ ^2 f°^ each half of the H2 doublet was 1.0 Hz, in agreement with the expected small value for J if 41 were exo . When F, was irradiated, the H^ H-,H2 — b 2 doublet collapsed to a sharp singlet, and the doublet of doublets for H became a doublet, retaining only the larger cis-vic coupling (J^ „ ) . Conversely, when F a 1 was irradiated, the H^ doublet was unchanged, and the remaining doublet for H, showed only the small trans-vie J . This experiment demonstrated the utility of hetero^ 2 19 nuclear decoupling in confirming F nmr assignments as well as determining the extent and nature of long range 19 1 F H couplings, and by performing such an experiment on 4_1, we confirmed that our W-, ,„ measurement of 1.0 Hz for J,, ,, was a maximum value. "1^2 The use of nmr shift reagents with compounds in the general class we were studying seemed to be appropriate, since, as a rule, the rate of shift of a given H resonance is inversely proportional to the distance between the lanthanide metal atom and the proton in question. In compounds such as 4j^, with two possible stereoisomers, it was hoped that the rates of shift for exo vs endo protons could be correlated, once the corresponding rates for a compound of known stereochemistry had been ascertained. As our reference compound, 3_4 was used since it had the prerequisite oxygen bridge (for a Eu(FOD) metal coordination site) as well as protons on the cyclopropane ring that were known to

PAGE 57

49 be endo (for details of the method, see Experimental) , A comparison of the rates of shift (k) for protons in 34 and 4^ is given in Table II. The overall trends 'in the Table VI Comparison of Eu (FOP) nmr shift results for 34^ and 4_1 avg 0.774 1.74 0.603 0.645 avg 0.436 3.97 0.00 0.0064 data of Table II are in agreement for exo structures 34 and £1, in that the signal for H„ in both compounds exhibits the highest rate of shift. Also, k for 3_4_ and for 41 is 1 much smaller than k^^ , but if the k /k ratio is calculated, it has values of 2.25 for 3^ and 9.11 for £L. In quantitative comparisons of this type, a closer correlation V70uld be desirable and necessary if the method is to be more generally applicable. The discrepancy in k /k for 34_ and 4j^ is most probably 2 1

PAGE 58

50 due to a difference in the geometry of complexation of Eu(FOD) by the two compounds. It is known that Eu (FOD) ^ 1 9 will weakly coordinate to F (and produce contact shifts 19 53 m the F nmr spectrum) , so that weak secondary coordi19 nation with F m 21 and 41_, as shown below, might cause a slight off-centering of the Eu atom with respect to the Eu(FOD) Eu(FOD) 41 oxygen bridge, with the Eu atom residing more of the time syn to the cyclopropane ring. If this is the case, the similarity of k and k in 3^ comes as no surprise, nor 3 ^^4 do the negligible values for k^ and k.^ in 41 seem unusual. H3 H4 — Speculations of this type may provide satisfying explanations in individual cases such as the ones above, but these same rationalizations undermine the generality of the method. However, the other evidence obtained from W, ,„ measurements and heteronuclear decoupling experiments plus the chemical analogy between 40^, 4_1, and similar compounds known to be exo leaves little doubt that 4_0 is the exo adduct of 15 and isobenzofuran . As an interesting sidelight, 4]^ can also be recognized as a precursor to 1 , 1-dif luoronaphthocyclopropene (42^) , with the proposed conversion formally

PAGE 59

51 considered as an overall loss of water from 41. Vogel 54 et al., had previously prepared 1 , 1-dif luorobenzocyclopropene (4_3) , so that 42_ would be an interesting extension 43 of these authors' investigation into the question of bond fixation in benzo-annelated cyclopropenes . The actual conversion of 4]^ to 42_ was thought possible in light of 55 . recent work m which 1 , 2 , 3 , 4-tetrahydronaphthalene-l , 4endoxide was converted to naphthalene with triphenylphosphine dibromide via an intermediate dibromo compound, as shown below. Under the conditions of the reaction of 41 with SiO triphenylphosphine dibromide and subsequent silica gel

PAGE 60

52 chromatography, the oxygen bridge was indeed cleaved, but with concomitant ring opening, so that the only isolated product derived from 4_1_ was not 42_, but 6-bromodif luoromethyl) naphthalene {44). That the gem -dif luorocyclopropane -^(-> il 41 44 ring was opened (apparently by Br ) under prolonged heating was not too surprising due to the probable susceptibility of the gem -dif luoro carbon atom to nucleophilic attack. Turning to reactions of 1^ with acyclic dienes. Law and Tobey had prepared the adduct _45_ of 1_5 with 1,3butadiene, which was converted to 1 , 1-dif luorobenzocyclo54 propene by Vogel and coworkers. Due to the lack of substituents on the butadiene moiety in ^, the stereochemistry of addition is irrelevant, but there still exists the possibility of conformational isomerism. Law and Tobey 19 represented 4_5 as 45b only, based on the F couplings to 35 45a the methylene protons (see Table I>5 . According to these

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53 authors, 4 5b has fewer steric interactions than 45a and is thus the preferred conformation. Of relevance to our work is their comment that the J _ data seem to F H indicate that ^ exists in a "flip form opposite..." to the conformation of this structure if an oxobridge were present. That is, the bicyclic moiety in £5 appeared to them to be opposite in structure to this same group in the furan adduct of 15_. However, since the furan adduct (20a) is in fact exo , their analysis would lead to a prediction of the less stable conformer 45a as the species most consistent with the nmr data. In order to resolve this question of stereochemistry, if possible, and to investigate a cycloaddition of ]^ to an acyclic, unsymmetric 1 , 3-butadiene for comparison to the furan series, we elected to use 1-methoxy-l , 3-butadiene in a reaction with 1_5. The presence of the methoxy substituent introduces the possibility of stereoisomerism in the adduct 46_, in addition to the previously existing possibility of conformational isomerism in each stereoisomer, The resulting four possible structures for 4_6(a-d) are shown below, and are classified as exo or endo with respect to the endo methoxy 46c

PAGE 62

54 OCH exo methoxy 46b 46a 46c 46b 46d Br endo methoxy 46d placement of the methoxy group. Due to steric repulsions, the folded forms 46a and 46c would be expected to be less stable than 46b and 46d . Therefore the choice of which isomer was actually produced in the reaction was narrowed 19 to one of the latter two structures. The F nmr spectrum made it possible to assign 46b as the correct structure, since F (at lowest field) appeared as a doublet of triplets (Jp F^ = 155 «^' ^F H = ^F H a b a a ax b b = 3.2 Hz) and F appeared as 2.4 Hz), as shown below with a doublet of doublets (J 19 the observed F chemical shifts. The analogy between J b b 138.51 (d of d) 113.92 (d of t) 46b in 46b (2.4 Hz) and F in 20a (2.1 Hz), shown by the b 2 darkened lines below, and the larger value for the triplet coupling J (3.2 Hz), which was not possible in 20a, a x ,a ~

PAGE 63

55 46b 19 of course, argued for structure 46b . The F nmr assignments in 46b were confirmed by reduction of the methine cyclopropyl bromines with tri -n-butyltin hydride, which produced the dihydro compound 47 which had the characteris19 tic triplet for F m the F nmr with cis -vic coupling 19 J . of 14.0 Hz. Unfortunately, the remainder of the F a c 46b (n-Bu) ^SnH (t-BuO) 2 , A -> nmr spectrum, as well as the H nmr spectrum, proved to be too complex to allow further evaluation of other coupling constants. Interestingly, a minor artifact of the reduction was a monobromo product, which could be identified as 48 1 19 1 using H nmr chemical shifts and FH coupling constants. The chemical shift of H (64.16) in 48_ was quite close to that of H in 47 (63.91). However, H , in 48 appeared at X — a, b — "^"^ 62.87, shifted downfield more than 0.5 ppm by the vicinal cyclopropyl bromine atom, relative to H , in 47, which a , b —

PAGE 64

56 46b > 47 a b Jp H = 15-0 a c Jp jj =3.35 a X ,a 19 appeared at 62.33. Also, F in the F nmr spectrum of 48 appeared as a doublet (J^ „ = 161,0 Hz) of doublets — r r a b (Jp ^ = 15.0 Hz) of triplets (J^ ^ = 3.35 Hz), and a c 1 Q a X, a was the F at lowest field (697.74). The monobromo product which best fits these data is 4_8. Therefore, the results obtained for the reaction of 15_ with 1-methoxy-l , 3butadiene correspond to an exo cycloaddition , assuming that 1-methoxy-l , 3-butadiene is trans . Also, this reaction demonstrates that information regarding stereochemistry of [4+2] additions of perhalocyclopropenes to acyclic 1,3dienes can be obtained if the diene has a nonsymmetric substitution pattern. Correct deduction of the product structure will give an indication of relative conformational stabilities and may provide clues as to the structure of the transition state leading to the observed product. But quantitative evaluation of all of the steric and electronic factors in a [4+2] cycloaddition reaction such as the one above is a complex undertaking, so that care must be taken not to attribute total control of the transition state geometry to any single factor, excluding other subtler influences

PAGE 65

57 which may be the real controlling factors. As outlined in the Introduction, alkyland arylcyclopropenes have been known to react with fulvenes in 17 18 a [4+2] manner, ' and the resulting adducts can be further modified to give materials that are useful in structure-reactivity studies such as solvolysis of alcohol derivatives and ketone decarbonylation. Specifically, 17 Tanida, using a 6 , 6-dimethylf ulvene and cyclopropene , synthesized endo -tricyclo [3.2.1.0 ' ]octan-8-one (5^) by way of oxonolysis of the 8(dimethylmethylene) compound 49, 1) 0. ^ 2) Zn, H + Since we had previously demonstrated that the methine cyclopropyl bromines in some of the furan adducts we had prepared could be reduced with tri -n-butyltin hydride, the application of the technique could be used in the synthesis of a 3,3difluoro derivative of 5j0, as shown in Scheme V. it should be noted that even though 5_0, derived from cyclopropene and 6 , 6-dimethylf ulvene, was proven to be endo by Tanida, the assignment of stereochemistry to 51a and 51b must be based on more than analogy to the hydrocarbon system. Also, our reactions to form 51a and 51b were run at 115° C, in contrast

PAGE 66

Scheme V 15 + R R R = 0, CH. -> 52a 52b to Tanida's work, which was done at room temperature or lower. This fact combined with the much greater ground 35 state stability of 1^ over cyclopropene means that our adducts were formed under conditions that may have been conducive to reversible formation of the more stable exo adducts . Since adducts 51a and 51b are the first reported products arising from a [4+2] reaction of a fulvene with a perhalocyclopropene, stereochemical assignments cannot be 19 based on F chemical shifts observed in these compounds without reference data for model systems of known stereochemistry. However, since these adducts were treated with

PAGE 67

59 the same reagents as was 20a, and since certain trends in 19 the changes in the F nmr spectra of products derived from 20a were noted earlier, some internal comparisons can be made in the sequence 51a, b : 52a, b : 5Ba,b . As shown in Table Vii, the chemical shifts for F in 52a and 52b are virtually identical, as are the analagous values for 6F a in 53a and 53b . This indicates the similarity in the Table vll 19 Comparison of F Nmr Chemical Shift Data 51a 6F 94. 4S a )F, 131.96 b 132.65 142.77 CHj?^r— CH 51b 6F --CH.

PAGE 68

60 environments for F in each of the pairs of compounds. Turning to the values for (""F , if both 51a and 51b were endo, the differences in the changes in chemical shift for F, should also be small, but what was observed proved to be substantial differences in the values for 6F, , when comparisons were made for 52a and 52b , or 53a and 53b. This indicates rather dissimilar environments for F, in b these compounds, whereas the environments for F in the same compounds were shown to be quite comparable. If both adducts were endo, the values of 6F and 6F, ought to be a b ^ almost identical for 53a and 53b, as shown below, instead 53a (as endo) 53b (as endo) of exhibiting the differences shown in Table III. Therefore, 19 based on these internal comparisons of F chemical shift values, adducts 51a and 51b appear to be exo . The other criteria useful in specifying stereochemistry are not as applicable in these two cases. First, the observance of or the lack of coupling between bridgehead protons and methine cyclopropyl protons in 53a and 53b is obscured by the fact that the bridgehead protons in 52a and 52b , and 53a and 53b , all appear as broad multiplets. All that can be said is that

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61 W^,^ f°^ 52a and 53a are both 6 Hz, and that W , for 52b and 53b are both 5 Hz. While these W , values for 53a and 53b could accommodate a coupling of 3-4 Hz for bridgehead proton-methine cyclopropyl proton coupling, the fact that the values do not change upon debromination is supportive of the proposed exo structures. Also, the complexity of the H nmr spectra and the extensive H H couplings in these compounds renders heteronuclear decoupling almost useless, since the values for W, ,_ would not change 19 1 much even if all F H couplings were eliminated. While a Eu (FOD) ^ experiment might be of some help in assigning stereochemistry in the ketone 5^, it must be mentioned that no Eu (FOD) shift data are available for the known epimeric ketones in the non-f luorinated series for comparison, so that this technique is of limited utility. Until such data are amassed, both for model systems (for example, exo and endo 2 4 tricyclo [ 3 . 2 . 1. ' ] octan-8-one) and for ketone 5_4 (as of this writing, 5_^ has not yet been characterized) , the only indications that both 51a and 51b are exo adducts are chemical intuition (in light of the severe reaction conditions) and 19 more importantly the F nmr chemical shift behavior discussed above. If 5_4 does, indeed, prove to be exo, the synthesis 2 4 of the epimer, endo -3 , 3-dif luorotricyclo [3.2.1.0 ' ]octan8-one (5_5) , required for investigations into the effect of 2 4 fluorine substituents on reactivity in the tricyclo [ 3 . 2 , 1 . ' ]octyl system, becomes much more difficult, since the exo isomer (54) should be obtainable by alternate routes. Also, as will

PAGE 70

62 be discussed later, endo 55 may easily isomerize to exo 54 at moderate temperatures. At this time, and taking into consideration the results discussed above for the reactions of 15_ with 6 , 6-diphenyland 6 , 6-dimethylfulvene , the next logical step in our stereochemical studies of the [4 + 2] reactions of 15^ seemed to be an attempt to force this cyclopropene into reacting with a diene so as to produce an endo adduct. The diene we chose was spiro 4.2 heptadiene (5_6) , since the spiro methylene groups would appear to place severe steric restrictions on any cyclopropene reacting via the exo mode (see below) . + a -> 56 Substantial non-bonded interactions should develop between the cyclopropene methylene substituent and the apical cyclopropane hydrogens syn to the reacting cyclopropene molecule. On steric grounds, then, an argument might be made for the

PAGE 71

63 reaction of 5_6 with 1^ to proceed to give an endo adduct. Also, the adduct of cyclopropene with _56 was reported by 22 LaRochelle and Trost to be endo , based on the similarity of its H nmr spectrum to other endo adducts of cyclopropene. Conversely, and also on chemical grounds, the exo adduct ( 57a ) of 5_6 and 1_5 may well be the more thermodynamically stable isomer, despite the steric interactions mentioned above. The reaction of 5_6 with 15^ was initially 57 57a attempted in CCl. at 55 C, but the reaction was sluggish at the concentrations used, so that prolonged heating at 55 C proved necessary for complete reaction. Nevertheless, 57 (57a) was isolated, and the spectroscopic and analytical 19 data for it were accumulated, including the F nmr chemical shifts. The technique used previously to firmly establish 19 F nmr assignments, that is, reduction of the methine cyclopropyl bromines with tri -n-butyltin hydride, was again applied to adduct _57 ( 57a ) , to give 58_ (58a) . At this point, we had 19 firmly established F chemical shift data for both the adduct and its debrominated product, as well as H nmr data for both compounds. The chemical shift data alone for these two

PAGE 72

64 compounds do not allov-/ for the unambiguous assignment of exo or endo stereochemistry, but comparison of these data to data from the adduct of 1^ with cyclopentadiene of known exo stereochemistry leads to the tentative assignment of exo stereochemistry in this case (that is, 57a and 58a ) . First, measurements of W , for the bridgehead protons in 57a and 58a gave values of 7 Hz and 6 Hz, respectively, indicating that any coupling from the methine cyclopropyl protons to the bridgehead protons in 58a is most likely small. Also, in a homonuclear decoupling experiment on 58a , when the bridgehead protons were irradiated, the methine cyclopropyl proton doublet maintained a line width of 3 Hz, which again is contraindicative of significant coupling of the type mentioned above. Second, a heteronuclear decoupling experiment on 58a , in addition to confirming the assignments of F and F , revealed an interesting six bond coupling from one fluorine to only two of the four apical cyclopropyl protons. When F in 58a was irradiated, the doublet signal for the methine cyclopropyl protons collapsed to a broad singlet (W, ,^ =3.9 Hz), as expected, and no change was observed in the complex pattern for the apical cyclopropyl protons. However, when F, was irradiated, the W, ,2 fo^ the methine cyclopropyl doublet decreased to 2,4 Hz as expected (note that this again indicated small coupling to the bridgehead protons), but of more interest was the change in the spirocyclopropyl proton signals. The upfield

PAGE 73

65 group of three broadened lines, which remained unchanged when either F or F was irradiated, were assigned to the a D two protons anti to the gem -dif luo rocy clop ropy 1 group and situated above the double bond. The downfield group of six broad lines collapsed to three lines when the F, b coupling was removed, and measurement of J_ placed a 19 1 b syn value of 4 Hz on this long range F H coupling. If 58a were endo (that is, 58_) , as depicted below, with the observed J outlined, the alternate long range coupling b syn alternate, unobserved J FH as either J„ .. or even J„ „ , should at t , rl , r n . . b anti a anti, or syn least have been observed in the decoupling experiment. Similar analysis for the proposed exo structure 58a, as shown below, reveals that F, is in much closer proximity to the syn protons, to which it is coupled, than F , which is "s.

PAGE 74

66 situated away from both the syn and anti spirocyclopropyl protons. All of these observations can be correlated by the application of an empirically derived rule stemming 19 1 from observations of long range F H coupling made by 5 6 "S 7 S 8 Cross et al. ' ' For example, the observance of five bond coupling in 6-f luorosteroids is dependent on whether 19 the F atom is a or 3, as shown below. In 59, the -CH 19 59_ (6B-F) £0 (6a-F) resonance appears as a doublet, whereas in 6_0, no observable coupling of this type occurs. Also, in the 56, 66 -difluorocyclopropyl steroid 6_1, the methyl resonance is a doublet, indicating coupling to one, but not both, of the gem -fluorines, which is rather analagous to the situation seen for the exo compound 58a . Finally, in the cyclobutane 6_2, only F is observed to be coupled to the methyl group (which is in accord

PAGE 75

67 with the previous data if the conformation shown above is strongly preferred) , All of the above data v/ere condensed into a rule, useful for predicting long range F H coupling, which 19 1 states that " F H coupling will be observed only when a vector directed along the C-F bond and originating at the carbon atom can converge upon and intersect a similar vector directed along a C-H bond of the methyl ,.59 group, In fairness, this rule is not totally applicable to 58a , since the C-F vector bisects the angle formed by Hg -C-H^ , and does not directly intersect either C-H vector. However, since this coupling is most likely a through-bond effect, the simple convergence of the C-F b and C-Hg vectors may make the use of the rule justifiable for 58a . The six bond coupling that we observed in 58a is, in our opinion, the first example of the type of long range J^^ designated by Jefford as "intercalated". That is, in the intercalated arrangement the C-F vector bisects the H-C-H angle (as in 58a ) , whereas in the "opposed" mode. the C-F and C-H vectors intersect. The intercalated and ^FH opposed orientations as designated by Jefford for J are shov/n below H F 1*H opposed intercalated

PAGE 76

A third indication of exo stereocheraistry in 58a comes from comparison of the F nmr chemical shifts for 57a and 58a with the reference system obtained from the [4+2] cycloaddition of 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15_) with cyclopentadiene, which at room temperature gives only the exo adduct 63^, which can be converted to 64_ (also exo) by the use of tri -n-butyltin hydride, as shown. (The arguments for exo structures 63 15 + -> ^ 63 and _6£ will be given later and in relation to data from 19 other reactions.) The comparative F nmr chemical shift data are shown in Table VIII. What is pertinent is the Table VIII Comparison of F Nmr Chemical Shift Data 124.10 il.94 57a F, 127.82 b !1.07

PAGE 77

Table VIII Continued 69 F 131.72 b F 100.30 a 139.32 F 100.12 a 58a 64 similarity in 6F for 57a and 6_3, and 58a and 64, which in turn indicates the similarity of the environments for ^a """" these compounds. The much larger discrepancies for 6Fj_^ in 57a and 62, and 58a and G4_ are due to the differences in the bridge substituents in the two systems. In summation, then, 57a and 58a appear to be the most probable structures for the cycloadduct of 15_ and 5^, and for the product derived from the reduction processes, even though on steric grounds the endo structures (S^ and 58.) f in analogy to the cyclopropene adduct of 56., were thought to be the more likely of the two isomeric possibilities. As mentioned above, the [4+2] cycloadduct 63 of 15 with cyclopentadiene was prepared in CCl at room temperature. At first, the crude reaction mixture was catalytically reduced to 6^ to prevent decomposition, but subsequently it was found that 63_ could be purified by distillation at reduced pressure and fully characterized. In addition, both 6^ and 63 were treated with tri -n-butyltin hydride producing 6^ and 64, respectively. Finally, the phenyl azide adduct (6_7) of 63, was prepared. These transformations are illustrated in Scheme

PAGE 78

VI. The exo stereochemistry of 63, 64, 65, 66, and 67 Scheme VI 70 P (n-Bu) ^SnH a (t-BuO; 66 ^i. was unambiguously established by an authentic synthesis of 66 , to be discussed later. The H nmr and F nmr spectra of 6_3 exhibited some-tunusual features worthy of detailed 19 analysis. As expected, in the F nmr spectrum F appeared at lowest field as a doublet (W, , = 3.6 Hz; J^ ^ = 145.5 1/ ^ F F, a b Hz) , and in accord with earlier observations was assigned the position cis to the methine cyclopropyl bromine atoms. This assignment was confirmed in the usual manner after reduction with tri -n-butyltin hydride. On the other hand, the

PAGE 79

71 Fj_^ resonance, at highest field, was a doublet ( J ^ , ) of 'a 'b quartets of doublets. The quartet coupling was 3.2 Hz and the doublet coupling was about 1.2 Hz, Coupling of 3 Hz from F to the bridgehead protons (H ) agrees with our earlier data, and an additional (and coincidental) coupling of 3 Hz from F to H , as shown below, is also reasonable when the long range coupling discussed earlier is considered and the "C-F vectorC-H vector" rule is recalled. This argument leaves only a 1.2 Hz coupling to anti ^b"2 b anti J = 3.2 HZ b syn = 1.2 Hz Fj_^ to be accounted for, and the most likely mode of coupling is the five bond coupling J , as shown above. Turning -, b anti to the H nmr spectrum of 6_3, the assignment of the low field half of the bridge protons' AB system at 62.02 to H anti and the high field half at 61.32 to H is based on the syn expected shielding of H by the cyclopropane ring. The doublet for H^^. . had a W, ^^ = 4 Hz with J„ „ = 9.6 Hz. anci -i/ ^ H H , . syn anti The signal for H appeared as a doublet of doublets of syn triplets. As before, J H H ^ . syn anti 9.6 Hz, and J„ „ = 3.2 b syn Hz, leaving only the triplet coupling to be accounted for by JjT T, = 1»8 Hz. Also, in a decoupling experiment, when the syn 2

PAGE 80

72 U^ signal was irradiated, the triplet J^ ^^ coupling was syn 2 removed, leaving a doublet (J^^ ^^ =9.6 Hz) of doublets syn anti (Jp jj =3 Hz) for the H resonance. The long range F -, b syn ^y" H coupling detailed above was also visible throughout the series £3-62 whenever the signal for H was separate from the rest of the spectrum. d These findings are somewhat in contrast to long range 19^ 1„ t U coupling data reported for the analagous compound 71 by Jefford et al. According to their analysis of the 19^ -, 1 F nmr and H nmr spectra of 7d^, the following coupling constants were assigned. No mention was made of any coupling ^ .H H anti \ / syn p FH syn FH anti FH, = 3.6 Hz = 3.0 Hz = 3.5 Hz from the fluorine to the bridgehead protons (H ) , which is odd since in our adduct 63, J^ „ was found to be 3.2 Hz, b 2 Moreoever, the assignment of J^,, = 3.0 Hz in 71 also r H , . anti disagrees with our assignment in 63 of J =1.2 Hz — F, H . b anti Of course, 62 is an unsaturated system, whereas Tl^, as a saturated analog, could differ enough in geometry to cause substantial changes in values for long range J FH In summarizing the results of the cycloadditions of l,2-dibromo-3, 3-difluorocyclopropene (1_5) with cyclic 1,3dienes, it becomes necessary to state explicitly what was

PAGE 81

merely implicit in the preceding discussion. That is, in all cases the products that have been characterized represent isolated, purified substances, which of necessity must comprise less than the amount of material which would result from 100% conversion of starting materials. Also, most of the reactions were run under conditions highly conducive (as will be discussed shortly) to endo exo isomerizations . As a prime example, in the debromination of the 1 , 3-diphenylisobenzofuran adduct ( 38a /38) , the minor endo component (38) was either isomerized to the exo compound (38a), or the endo debrominated species was not isolated during the workup of the reduction mixture. Therefore, the formation of minor amounts of endo cycloadducts with 15 is not ruled out for any of the cycloadductions and in some cases their actual formation v/as confirmed (see Chapter II, section III. Isomerization Studies of Selected [4+2] Cycloadducts , p 80). Carbene Additions to the Bicyclo[ 2 . 2 . 1 ]-heptyl System The proof of structure for our Diels-Alder adduct 63, previously alluded to, consisted of conversion of 63 to 66, the saturated, debrominated f luorocarbon. It was noted that this same material, if it were exo, should be accessible by way of addition of dif luorocarbene (:CF ) to norbornene. This reaction was carried out using the procedure developed by Seyferth et al. for generating dif luorocarbene (which most likely exists as a carbenoid) . The material isolated from the dif luorocarbene addition to norbornene had an

PAGE 82

63 ^ > 66 :CF, 74 infrared spectrum identical to the infrared spectrum of 66 which was derived from the cycloaddition product of 15 with cyclopentadiene (see Scheme VI). At this point a brief discussion of carbene additions to the bicYclo[2.2.1 ]heptyl system is in order. When a carbene adds to norbornene, the sole product is the result of exo addition, ' due presumably to the steric hindrance to the endo pathway by the endo -5 , 6-hydrogens . There have been reports of halocarbene additions to norbornene, and in those cases where one or both of the halogens were fluorine, the thermally stable products (i.e, non ring-opened) were found to be exclusively exo . For example, f luorochlorocarbene (:CFC1), produced by the base catalyzed decomposition of sym -dif luorotetrachloroacetone , gave two products, 68 and 6_9, with 69^ arising from the rearrangement of 70. iCFCl > 68 CI 70

PAGE 83

75 Similarly, bromof luorocarbene (:CFBr) gave the analagous products 71 and 72 (with 72 derived from 73; 44 With ;CFBr > 71 Br 73 72 norbornadiene the steric inhibition to endo carbene addition is diminished and endo addition products with methylene have been reported. ^^ ' ^^ ' ^^ ' ^^ ' ^^ Halocarbene additions to norbornadiene would likewise be expected to give mixtures of exo and endo products. Two recent papers by Jefford and coworkers, ' dealing with the results of f luorocarbene additions to norbornadiene, not only confirmed the possibility of endo addition in this system, but provided H nmr data that proved quite useful in making stereochemical assignments in related tricyclic systems. 70 In the first paper, exposure of norbornadiene to difluorocarbene (generated at 80° C) resulted in isolation of only two products, 7^ and 75^. Also, when norbornadiene was reacted with chlorof luorocarbene (:CFC1) at 140° C, five ;CF. 80°C 74

PAGE 84

76 products were isolated, as shown below. The absence of 2 4 any endo -tricyclo [ 3 . 2 . 1 . ' ]octyl compounds is not surprisinc :CFC1 ^ 140°C CI in view of the stringent reaction conditions (140° C, 12 7 1 hours), as compared to Jefford's later paper, which recounts the results of the reaction of norbornadiene with dif luorocarbene at 20° C. In a series of experiments performed at 20° C, that is, under conditions non-conducive to isomerization of any of the reaction products, Jefford was able to separate and characterize the dif luorocarbene adducts of norbornadiene and to compare them to the analagous adducts of 7-methylnorbornadiene. H and F Nmr chemical shifts and """H "^^F long range coupling data enabled the structures of all products to be assigned with some degree of certainty. Norbornadiene and dif luorocarbene , at 20° C, form three 1:1 adducts; a homo-1 , 4-adduct (75), plus exo (74)and endo

PAGE 85

(7_6)-3,3-difluorotricyclo[ 3,2.1.0^''^ ]oct-6-en 77 :CF, 20°C 76 Similarly, 7-methylnorbornadiene forms four adducts with difluorocarbene; a homo-1 , 4-adduct (7_7) , as well as the exo anti (7_8)-, endo anti (7_9)-, and endo-syn (80)-3,3difluoro-8-methyltricyclo[3.2.1. ' '^ ]oct-6-enes , as shown below. Accurate structural assignments in these tricyclic CH. adducts were expedited by the presence or absence of long 19 1 5 range F H coupling, labelled J^^^ by Jefford, amounting to 8.5 Hz, and present only in those compounds having the

PAGE 86

requisite structural features, namely, an endo-gemdif luorocyclopropane ring and a proton on the bridge anti with respect to the cyclopropane ring. Similar long 19 1 range F H coupling (9.8 Hz) was also observed in the tetracyclic products 7_5 and Tl_, due to the presence of the same chair cyclohexane 1 , 4-diequatorial F H arrangement, as shown below. Only the endo tricyclic adducts 76 19 1 and 8_0 display long range F H coupling of this magnitude, H^ .H The lack of J^.^^ in 19_ is due, of course, to the presence of the anti methyl group. If the data presented by Sargeant for the cycloaddition of 1, 3bis ( trif luoromethyl ) 3, 3-cyclopropene (17) with cyclopentadiene, which was discussed earlier (see Introduction, section III. Perhalocyclopropenes as Dienophiles , p 12 ) , is now reexamined with regard to long range 19 1 F H coupling, it becomes apparent that the two epimeric cyclopentadiene adducts of 1_7 should indeed be assigned the structures 27a and 28a , as we had suspected earlier. This reversal of the assignments made by Sargeant is based on the fact that only 28a (endo) exhibits a J^ „ of 8.5 Hz, and F H^ a f thus our earlier revision of the exo and endo assignments

PAGE 87

79 was entirely in order. 71 As a part of this same work, Jefford also studied the thermal behavior of 74^ and 7_6, and found that endo-76 isomerized at 60 80 C to exo -74. Therefore, the fact that we isolated only the exo adduct 6_3 of cyclopentadiene and 15^ by distillation is reasonable. Further, as Jefford points out, the facile isomerization of 16_ to 7_4, plus the 19 1 observation of the 8.5 Hz F H coupling in 7_6 only, leads inevitably to a reassessment of the isomerization work 31 done by Sargeant discussed earlier. Again, as we had suspected, the reassignment of the stereochemistries of Sargeant 's Diels-Alder adducts to 27a and 28a now makes their thermal behavior also seem more chemically sound. Thus, the reaction of 17_ with cyclopentadiene and the subsequent isomerizations of the products is most correctly represented as shown below. 65°C CF CF. 17 2
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80 Isomerization Studies of Selected [4 + 2] Cycloadducts The observation of endo to exo isomerization (76 74) by Jefford under relatively mild conditions (60° 80° C) prompted us to reinvestigate the behavior of 20a under comparable conditions. Our approach to the problem was twofold; first, the reaction of 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15) with excess furan was run at 25°, 50°, and 75° C. The crude reaction mixtures were then examined using H nmr for completeness and by F nmr for the detection of the exo ( 20a ) and endo (20) isomers. The structure for endo 20 was evident from the H and F nmr data (see Table IX) . The "'"H nmr spectra for exo 20a and endo 20 appear to be identical, and the ""-^F data for endo 2_0 are consistent only with an unrearranged tricyclic structure with Jp^pj^ = 143.0 Hz, and J^^^^^ = 2.2 Hz. Second, a sample of 20a , verified by F nmr to contain only exo 20a, was heated at 80° C in the presence of excess furan, and the ^F nmr spectrum of the resulting solution was recorded. Also, an nmr sample of the exo isobenzof uran adduct (40) was heated at 80° C for one week and then analyzed by F nmr. The results of these experiments are shown in Scheme VII, The failure of the isobenzof uran adduct 4_0 to isomerize is not too surprising, if the mechanism for exo / endo equilibration consists of a retro-Diels-Alder reaction followed by recombination to give an equilibrium ratio of products. In order for 40_ to undergo such a retro-cycloaddition, the

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Br 15 Scheme VII 25°C exo only 50°C exo only 75°C ^ exo/endo = 2.69/1.0 o°r R T > exo/endo = 3.3/1.0 > 2.64/1.0 80°c 1 week -^ exo only aromaticity of the benzo-moiety in £0^ would have to be disrupted, so that this pathway v/ould seem to be unlikely to occur with 40. Second, the likelihood of a retro-Diels-Alder reaction taking place in the 20/ 20a system is greater than with 40 due to the small gain in aromaticity if furan were formed

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from either stereoisomer by way of the retro-cycloadclition pathway. Thus, a possible mechanistic rationale for the behavior observed for 20a is that this exo isomer, under prolonged heating, isomerizes partially to the endo isomer 2^ via retro-cycloaddition to furan and JL5 followed by readduction, this process continuing until the 2.7/1.0 exo/endo ratio reflecting the relative thermodynamic stabilities of 20a and 20_ is obtained. The kinetic product of this cycloaddition appears to be the exo adduct 20a, since at lower temperatures, 20a was the only product observed in the F nmr spectrum. Since endo -20 is less stable than exo -20a, it is also reasonable to assume that 20_ should undergo a retro-DielsAlder reaction more easily than 20a., which helps to account for the apparent fact that Law and Tobey"^^ in their original work did not observe any endo material when they distilled their crude reaction mixture. The exo adduct, being more volatile (and also more stable) was the material that they collected, thus leaving an endo enriched pot mixture, which, of course, could then have isomerized to the equilibrium mixture. The net result of these processes would be a net distillation of only the exo adduct 20a . When we attempted to isolate the endo material by preparative gas chromatography, isomerization on the column (at 100° C) probably occurred, since we were only able to obtain a sample comprised of mostly (-60%) endo material. This sample proved to be stable to further isomerization in the absence of furan and at room

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temperature, so that we were able to collect H nmr and 19 F nmr data for the endo compound 20. The isomerizations of some of the other adducts of 15 could be studied by similar techniques, were it not for the fact that the dienes, once formed in the retro-cycloaddition, would tend to dimerize rather than re-form DielsAlder adducts with 15_. Also, since the isomerizations of endo adducts to their exo isomers has been shown to occur under mild heating, the isolation and characterization of endo products will be difficult. Therefore, in our proposed syntheses of the epimeric 3 ,3-difluorotricyclo[3 .2.1.o2 '4]Q^I-^j-;_8_Qj-^gg^ ^^^ gj^^o material (55^) could well isomerize to the exo isomer (54) before loss of carbon monoxide could occur, as shown below. This possibility would make the study of the decarbonylative reactivity of 5_5 and compounds derived from them difficult if the isomerization pathway were dominant. Synthetic Studies of 3 , 3-Dif luorocyclopropene One solution to the problem of synthesis of the endo

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84 isomer 55 would be to react 6 , 6-dimethylf ulvene with a gem-difluorocyclopropene having a greater reactivity than 15_, so that a lower reaction temperature (more conducive to endo adduct formation) could be used in the initial cycloaddition. The obvious choice for this dienophile is the parent compound, 3 , 3-dif luorocyclopropene (87), which has not yet been reported. We have attempted the synthesis of 8;^ and one of the more promising synthetic routes we devised is outlined in Scheme VIII. The reaction of 15 Scheme VIII o o o Br H Br 15 -> Br Br '^;u^F, (n-Bu) SnH ^ -> / with anthracene required prolonged heating at 130° C, increasing the probability of unwanted side reactions. Instead of the desired Diels-Alder adduct 8_1, we obtained the ring

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85 opened isomer 83_, which probably arose from the rupture of one of the peripheral cyclopropane bonds after the initial adduction of 15_ by anthracene had taken place. The ''"H nmr spectrum of 83^ consisted of two singlets for the bridgehead protons plus a group of complex aromatic absorptions, while the """^F spectrum consisted of only a singlet at 647.01, which is consistent with the ring opened structure but clearly eliminates the original Diels-Alder adduct structure 81 . Reduction of the two bromine atoms in 8_3 could not produce, of course, the desired compound 8_2, but instead gave the ring opened analog 8_4. The 100 MHz "'"H nmr spectrum of 8_4 revealed a triplet at 6.1 with J = 56 Hz, which is consistent with the presence of a -CF2H group in the molecule. Also, the remainder of the ^H nmr spectrum, as well as the F nmr spectrum supports structure 8_4. These transformations, that took place instead of the desired reaction sequence above, are shown in Scheme IX, Thus, the ring opening reaction of 83^ to give 8_3 prevented this approach Scheme IX 000 + 15 > [81 (n-Bu) SnH

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86 from yielding the desired precursor to 3 , 3-dif luorocyclopropene (87_) . Another promising approach to ^ required the synthesis of 1,2 bis (trimethylsilyl) -3 , 3-dif luorocyclopropene (86) , by the addition of rCFn to the alkyne 8_5, as shown below. Hydrolysis of the trimethylsilyl substituents should give (CH^) ^Si-C=C-Si (CH ) Si (CH ) 86 the desired 87^. Dif luorocarbene addition at 80° C gave an unstable material in low yield that appeared to be 86, but this cyclopropene failed to react with any diene, including isobenzof uran generated in situ . Also, an attempted hydrolysis of the trimethylsilyl groups, using a KOH-methanol solution failed to produce 87 or any other volatile products.

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G O e o u CM K [m tj b^ fD 1^ I-) (0 X! iJD m II II II 12 i-H i-l t. K K [ii P^ p-i Dli i-D 1-:) f-) f-3 K fc

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89 tn

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90 tn

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91

PAGE 100

92 o Pa e o u o o

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93 c 3 O o u

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94 r! T3 c

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95 K

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96 K

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97 c o a. E o u M

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CHAPTER III EXPERIMENTAL General All melting points were taken on a Thomas-Hoover melting point apparatus and are uncorrected. All micro analyses were performed by Atlantic Microlabs, Inc., Atlanta, Georgia. Infra-red spectra were recorded either on a Beckman IR-10 Spectrophotometer or a Perkin-Elmer 137 Sodium Chloride Spectrophotometer. Solid samples were run as KBr v/afers in a Wilkes Mini-Press, and liquid samples were run either between NaCl windows (Neat) or in a Wilkes Mini-Cell v/ith AgCl windows. All ir bands are reported in cm , and have been corrected to polystyrene calibration (1601.1 cm" and 906.5 cm reference peaks). Ultra violet spectra were recorded on a Carey-15 UV-Visible Spectrophotometer. Mass spectra were recorded either on an Hitachi PerkinElmer NMR 6E Mass Spectrometer or an Associated Electronics Industries (AEI) Model MS-30 Mass Spectrometer, and were recorded at 70 eV. Gas chromatography (both analytical and preparative) was performed using a Varian Aerograph 90-P instrument with a thermal conductivity detector. Proton nmr spectra were recorded on a Varian Associates 98

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99 Model A-60, 60 MHz nmr spectrometer or a Varian Associates Model XL-100, 100 MHz nmr spectrometer. All ''"^F nmr spectra were recorded on the XL-100 instrument at 94.1 MHz and all heteronuclear decoupling experiments, as well as Fourier Transform spectra were also done on the XL-100 instrument. 1 19 All H and F nmr data, unless quoted in the text of a particular experiment, appear in Table IX. Preparation of Pentachlorocyclopropane . ^^ A five-liter, three-neck round bottom flask was equipped with a mechanical stirrer and a reflux condenser. Trichloroethylene (2.5 1) and 1, 2-dimethoxyethane (750 ml) were placed in the flask and brought to reflux. Sodium trichloroacetate (1600 g, 8.63 mol) was added in 200 g portions over a period of about two days. The mixture was stirred and refluxed until CO evolution ceased (usually an additional 24-36 hours). The flask was then cooled and the mixture was filtered to give a blackish-brown solution. After evaporation of excess trichloroethylene and dimethoxyethane, the brown residue was distilled under reduced pressure to give pentachlorocyclopropane (406 g, 22%; bp^^ 64° 66° C, lit. bp^ 56° C) . Nmr 63.91 (s, IH) . Drying the refluxing solution by means of a Dean-Stark tray did not seem to affect the yields. Use of powdered sodium trichloacetate (Eastman, U.S. pellets) increased the reaction rate, but also did not affect the yields. Preparation of Tetrachlorocyclopropene (11^).^^ A one-liter.

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100 three-neck Morton flask was equipped with a paddle blade stirrer, a thermometer, and a reflux condenser. Potassium hydroxide (101.0 g, 1.80 mol) in 120 ml of water was placed in the flask and pentachlorocyclopropane (150.0 g, 0.66 mol) was added. On initiation of vigorous stirring the bright yellow reaction mixture became exothermic. The temperature of the reaction was maintained at 90° 95° (note 2) by periodic ice-water bath cooling. After about 10 15 minutes, the solution abruptly turned yellovz-orange , the temperature dropped, and a vapor escaped from the top of the condenser. The stirring and cooling was continued while 150 175 ml of water and 75 ml of concentrated hydrochloric acid were added from an addition funnel. Stirring was stopped, and the lower organic phase was drawn off and dried (Na SO ) . The aqueous phase was extracted with methylene chloride (3 x 50 ml), and the extracts were dried (Na SO ) . The original organic phase and the methylene chloride extracts were combined, the solvent was removed (aspirator) and the residue distilled at atmospheric pressure, under nitrogen, using ice-water cooled receivers and a 6" vigreaux column (microsetup) to give tetrachlorocyclopropene (11) as a clear, colorless, lachrymatory liquid; 50.55 g, 43%; bp 133.0° 135.5° C, lit. bp 129° 130° C. The infrared spectrum (Neat, AgCl) showed absorption bands at 1735 (m) , 1195 (w) , 1150 (s), 1120 (w) , 1055 (s), 895 (w) , 850 (w) , 805 (w) , 755 (s), 690 (w) cm~^: lit. 1810 (w) , 1300 (w) , 1190 (w) , 1148 (vs,s), 1100 (w) , 1055 (vs,s), 817 (w) , 753 (vs,b), 690 (m,s) cm"""-.

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101 The best yields were obtained using a Morton flask with a paddle blade stirrer. If the temperature is kept below 90 (85 90 ) the reaction takes about 15 20 minutes, and the yield is lower. Preparation of 1 , 2-dichloro-3 , 3-dif luorocyclo propene (14) and 1,2 , 3-trichloro-3-f luorocyclopropene (13). Tetrachlorocyclopropene (11) (10.3 g, 0.057 mol) and antimony trifluoride (12.6 g, 0.075 mol) were placed in a distillation flask and stirred while gradually heating to a maximum bath temperature of 110° C. Approximately 5 ml of a colorless liquid distilled from 50° 95° C. Fractionation on a 6" vigreaux column gave 1 , 2-dichloro-3, 3-dif luorocyclopropene ( 14 ) (2.27 g, 27%, based on tetrachlorocyclopropene (11), bp 54 57 C) , and a higher boiling fraction (bp 60° 95°) that by IR analysis contained tetrachlorocyclopropene (11) , l,2-dichloro-3, 3-dif luorocyclopropene (1£) and 1,2,3-trichloro-3-fluorocyclopropene (13^) (0.92 g) . It was subsequently found that the conversion of tetrachlorocyclopropene (11) to l,2-dichloro-3, 3-dif luorocyclopropene (1_4) could be made more efficient by using the vigreaux column for the original "crude" distillation, and by keeping the bath temperature less than 95° C. In this fashion, 20.6 g tetrachlorocyclopropene (1^) gave 6.30 g 1 , 2-dichloro-3 , 3-dif luorocyclopropene (1^) (39%). Preparation of Tetrabromocyclopropene (12_) . A three-neck, 250 ml round bottom flask was equipped with a magnetic stirrer

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102 a 125 ml addition funnel, a reflux condenser, and a nitrogen inlet. Tetrachlorocyclopropene (14) (58.4 g, 0.329 mol) was placed in the flask and boron tribromide (Ventron, 100 g, 0.398 mol) was added with stirring under a nitrogen flow over a 0.5 hour period. The pale yellow solution became warm, and BCl was emitted from the condenser (and was led to the back of the hood) . After the addition of boron tribromide was complete, the orange mixture was stirred and swept with nitrogen until the BCl evolution had ceased (ca. 10 15 minutes) . The volatile components were removed under vacuum (ca. 5 mm Hg) and the residue was distilled giving tetrabromocyclopropene (12) (100.2 g, 87%; bp^^ 90° 94° C, lit. bpQ_^_Q^^^ 70° 95° C) The infrared spectrum (Neat, AgCl) displayed absorption bands at 1760 (m) , 1137 1120 (d,s), 1077 (m) , 1000 (s), 662 (s), 580 (w) , 490 (s) cm"^; lit. 1757, 1135 1121, 1057, 1002, 664. Preparation of 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15) 28 Antimony trifluoride (Fisher, technical grade, 79 g, 0.442 mol) and a stirring bar were placed in a 100 ml round bottom flask. Tetrabromocyclopropene (12) (100.0 g, 0.28 mol) was added and the flask was connected to a distillation apparatus and the mixture was heated to 6 0° C. In some cases , the initial reaction was quite exothermic , and had to be moderated with an ice-water bath. A white cloudy vapor v;as given off as heating was continued and the bath temperature was rinsed

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103 until distillation began. After all the distillate (15 20 ml) was collected in a round bottom flask cooled by an ice-water bath, it was immediately redistilled under N , giving 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15^) (36.6 g, 55.5%; bp 92° 96° C, lit. bp 105° C). The infrared spectrum (Neat, AgCl) displayed absorption bands at 1727 (w) , 1300 (b,s), 1070 (b,s), 823 (ra) , 717 (w) , 549 (w) , 512 (w) , 479 (w) cm"-"-; lit. 1724, 1429 (w) , 1368 (w) , 1304, 1217 (w) , 1073, 823, 717 cm"""-. Reaction of 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15) with Furan-Preparation of 2 , 4-dibromo-3 , 3-dif luoro-8 -oxatricyclo2 4 15 [3.2.1.0 ' ]oct-6-ene (20a) . Freshly distilled furan (1.5 g, 6.2 mmol) and 10 ml of carbon tetrachloride (Spectrar) were placed in a sealed tube (Fischer-Porter) and heated to 80 for 24 hours. The tube was cooled, opened and the solvent and excess furan were evaporated to yield a dark brown residue which was percolated through a florex column with pentane. Evaporation of the pentane left an orange wax, which on sublimation at reduced pressure (10 15 mm Hg, ca. 50 C) gave white needles of 2 , 4-dibromo-3 , 3difluoro-8-oxatricyclo[ 3.2.1. ' ]oct-6-ene ( 20a ) (0.8 g, 43.4%, mp = 61 62°, lit. mp = 95°). G.C. examination on a 5', 10% SE 30 column at 100 showed one peak. The infrared spectrum (KBr) displayed absorption bands at 3015, 1400, 1290, 1235 (w) , 1220 (sh), 1190, 1110 (w) , 1090 (w) , 1020, 1000, 950, 930, 912, 860, 828, 760, 735, 711, 670, 660, 548

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104 cm" ; lit. 3020, 1380, 1295, 1215, 1200, 1020, 1000, 917, 829, 710, 670, 550 cm . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 304 (0.062), 302 (0.115), 300 (0.069), 256 (19.3), 254 (38.6), 252 (20.2), 223 (32.2), 221 (33.4), 155 (98.4), 153 (98.8), 114 (100.0). Anal . Calcd for C^H^OF^Br^: C, 27.84; H, 1.33; Br, 52.59; F + 0, 17.89. Found: C, 27.84; H, 1.38; Br, 52.39; F + 0, 17.39 (diff). Preparation of Phenyl Azide (31) .^^ m a 3-necked, 1 1 round bottom flask equipped with an overhead paddle blade stirrer, a thermometer, and a 125 ml dropping funnel were placed 55.5 ml of cone, hydrochloric acid and 300 ml of water. The solution was cooled with an ice-water bath and stirred while phenylhydrazine (33.5 g, 0.31 mol, MCB) was added over 10 minutes, at which time a thick cream colored solid (0NHNH -HCl) precipitated. To this stirred slurry at 0° C was added 100 ml of ether, then NaN02 (25 g) in 30 ml of water, over a period of 30 minutes with the temperature <_ 5° C. The crude mixture was then distilled, and the aqueous azeotrope was collected. When no organic material remained in the pot, the distillation was stopped, and the two phases of the distillate were separated. The aqueous phase was extracted with ether (3 x 50 ml) and the ether extracts were combined with the product. The ethereal solution was dried (Na^SO J , 2 4 ' the solvent was removed, and the residue upon distillation at reduced pressure gave phenyl azide (33^) (23.77 g, 64.4%;

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105 bp^ 4 9 50 C) , as a yellow oil which was stored under N at 0° C. Reaction of 2, 4-dibromo-3 , 3-dif luoro-8-oxatricyclo [ 3 . 2.1.0^''^]3 S oct-6-ene ( 20a ) with Phenyl Azide (3_1) . Phenyl azide (31) (0.400 g, 3.20 mmol), 2 , 4-dibrorao-3 , 3-dif luoro-3-oxatricyclo2 4 [3.2.1.0 ' ]oct-6-ene (20a.) (0.955 g, 3.16 mmol) and about 10 ml of CCl^ (Spectrar) were placed in a sealed tube (FischerPorter) and heated to 65 C for four hours. Upon cooling, a brown solid (1.00 g) precipitated, and was filtered. The filtrate was heated at 65 overnight, and a second crop of solid was obtained (0.138 g) . The combined solids were recrystallized first from hexane and then from benzene to give the adduct 32 (0.892 g, 67.2%, mp 186° 187° C) . The infrared spectrum (KBr) displayed absorption bands at 1596, 1498, 1476, 1448, 1407, 1390 (sh), 1360, 1310 (w) , 1276 (m) , 1228 (s) , 1180 (sh) , 1160 (w) , 1120 (br,s), 1103 (sh), 1070 (w) , 1040 (w) , 1005, 996 (d) , 966, 950 (sh), 937 (w), 920 (w) , 885 (w) , 870 (w) , 803, 781, 748, 730, 690 (w) , 660 (sh) cm~^. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 424 (0.50), 422 (1.03), 420 (0.52), 396 (0.12), 394 (0.23), 392 (0.14), 367 (0.6), 365 (1.0), 363 (0.8), 348 (0.3), 346 (0.6), 344 (0.3), 315 (7.6), 313 (7.5), 286 (8.4), 284 (8.6), 265 (6.6) , 263 (5.4) . Anal. Calcd for C^^U N^Br^OF^: C, 37.08; H, 2.15; N, 9.98; Br, 3 7.96; F + 0, 12,83. Found: C, 37.19; H, 2.17; N, 9.97; Br, 38.10; F + 0, 12.57 (diff).

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106 Single Crystal X-ray Analysis of Phenyl Azide adduct 32. The colorless crystals of 32_ grown from methylene chloride a re monoclinic, space group P2 /n, with a = 6.809{2)A, b = 13.432(3)A, c = 15.235(3)A, and B = 94.010(2)A. There are four molecules of C^^HgBr^N^OF^ per unit cell. Intensity data were measured on a Syntex PI dif f ractometer using graphite monchromatized MoK radiation and a -20 scan technique. The bromine atoms were located in a Patterson function and the remaining light atoms in a Fourier synthesis, Refinement by full matrix least-squares methods with all atoms anisotropic gave an R of 0.064. The addition of the hydrogen atoms and three additional cycles reduced R to 0.058 for the 1204 reflections with I >_ 2.0a (I) used in the analysis. The atomic numbering and molecular geometry of 32 are illustrated in Figure I (see p. 37 ) , which clearly establishes exo stereochemistry for both the phenyl azide moiety and the gem dif luorocyclopropane ring. The NlOo Nil bond length of 1.263 (15) A establishes the position of the double bond. Also, the internal cyclopropane bond (C2-C4) has a length of 1.551 (16) A, longer than either of the peripheral cyclopropane bonds (C2-C3, 1.480(19)A; C3C4, 1.487(17)A. 2,4 Preparation of 2 , 4-dibromo-3 , 3-dif luoro-8-oxatricyclo[ 3 . 2 . 1 . ] octane (33_) • In a 200 ml round bottom flask equipped with a magnetic stirrer and a reflux condenser were placed 2,4-dibromo-

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107 2,4 3,3-difluoro-8-oxatricyclo[3 .2. 1. loct-6-ene ( 20a ) (1.51 g, 5.0 nunol) , p-toluenesulf onylhydrazine (9.32 g, 50 mmol) diglyme (125 ml) , and triethylamine (15 ml) . The mixture was stirred and heated (at 80° C) under nitrogen for 8 hours. The mixture was cooled and poured into 200 ml of pentane. A lower dark brown oily layer was drained off and discarded and the pentane solution was washed successively with 5% H2SO4, 5% NaOH, and saturated aqueous NaCl solution. The pentane solution was dried (Na2S04, filtered, and the solvent removed, The oily residue was taken up in methylene chloride and washed with water. After drying, the solvent was removed under reduced pressure, giving long white needles (1.35 g, 89% crude) . Recrystallization from aqueous ethanol gave white crystals (3_3) (0.8180 g, 54%), Sublimation gave an analytical sample, mp 56° 57° C. The infrared spectrum (KBr) displayed absorption bands at 3000, 2963, 1469, 1427 (sh) , 1410 (s), 1359 (w) , 1313, 1299, 1289 (sh), 1238 (w) , 1217 (s) , 1189 (s) , 1130 (s) , 1064, 1029 (sh) , 1004, 989, 935, 906 (sh) , 901, 834 (s), 829 (sh), 817, 769, 758 (s), 687 (w) cm . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 307 (4.3), 305 (8.9), 303 (4.5), 250 (3.9), 248 (8.6), 246 (4.5), 225 (45.6), 223 (48.3), 198 (47.2), 196 (52.2), 115 (100.0), 96 (49.8). Anal. Calcd for C-7H5Br2F20: C, 27.66; 11, 1.99; Br, 52.58; F + 0, 17.76. Found: C, 27.92; H, 2.01; Br, 52.30; F + 0, 17.77 (diff ) .

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lOi Preparation of Tri-n-butyltin Hydride . "^^ To a stirred ether (250 ml) slurry of lithium aluminum hydride (6.0 g, 0.15 mol) in a 3-necked round bottom flask equipped with reflux condenser, magnetic stirrer, and a 250 ml dropping funnel, was added under N2, tri-n-butyltin chloride (38.5 g, 0.118 mol, Aldrich) in 100 ml ether over a period of 20 minutes. The mixture was heated to reflux under N2 for 2.5 hours, after which the flask was cooled with ice-water, and 0.5 g hydroquinone was added. Then, at 0° C, 12 ml of water was cautiously added, followed by 300 ml of a 20% aqueous solution of potassium sodium tartarate, which resulted in the formation of two phases. The ether phase was separated, the aqueous layer was extracted with ether (2 x 100 ml) and the combined ethereal solution was dried over Na2S04. The solvent was removed under reduced pressure leaving about 50 ml of a colorless solution. Vacuum distillation (caution; the product tends to foam a great deal during distillation) yielded tri-n-butyltin hydride as a slightly cloudy colorless liquid (31.4 g, 72%; bp^ _ ^ 90° 100° C, lit. bpg^^ 76° C). The IR spectrum showed a major absorption at 1810 cm""'(Sn-H) . Preparation of 3 , 3-d if luoro-8-oxatricyclo[ 3.2.1.0'^''^] octane (34) . 2,4-Dibromo-3,3-difluoro-8-oxatricyclo[3 .2.1. O^''^] octane (33_) (0.395 g, 1.30 mmol) , tri-n-butyltin hydride (1.13 g, 3.88 mmol), and a few drops of ditert -butyl peroxide vvere placed in a sealed tube (Fischer-Porter) and heated at 90° C for 24 hours. The clear solution was chroma tographed on

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109 alumina (MCB 80-200) with pentane. The first twelve fractions (10 ml each) contained alkytin residues. Elution of the product with 1:1 benzene : pentane afforded a yellow oil which on preparative glpc (5', 3% SE-30, T^q^l ^^° C, 30 psi) gave a colorless oil (3_4) (0.122 g, 64%). The infrared spectrun^ (Neat, NaCl) displayed absorption bands at 3060 (w) , 2998, 2960, 2920 (w) , 2880, 1676 (w) , 1465 (sh), 1442 (s) , 1410 (w) , 1319 (s), 1298 (w) , 1255 (s), 1221, 1208, 1145 (sh), 1130 (s) , 1071 (w) , 1022 (s) , 1012 (sh) , 980, 952, 932, 895, 860, 812, 779, 660 (w) cm"^. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 146 (1.90), 145 (0.58), 128 (1.1), 127 (2.6), 126 (3.2), 125 (4.3), 124 (3.2), 123 (4.3), 97 (54.4), 90 (100.0), 77 (37.2), 39 (27.3). Anal. Calcd for C7H8F2O: C, 57.53; H, 5.52; F + 0, 36.95. Found: C, 57.52; H, 5.61; F + 0, 36.87 (dif f ) . Preparation of 3 , 3-dif luoro-8-oxatricyclo[ 3 . 2 . 1 . 0^ ' '^ ] oct-6ene (35) . In a 10 ml round bottom flask chilled in an icewater bath were placed 3 , 3-dif luoro-2 , 4-dibromo-8-oxatricyclo[3.2.1.0^'^]oct-6-ene (3j4) (2.416 g, 16.78 mmol) , trin-butyltin hydride (5.82 g, 20.0 mmol), and one drop ditert -butyl peroxide. A magnetic stirring bar was added and the flask was tightly stoppered. The resulting yelloworange solution was stirred and heated for six hours at 45° C, The volatile product was distilled bulb to bulb, and the

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110 colorless oil purified by preparative glpc (5', 20% SE-30, ^col = 11'^° 20 cc He/min) to yield 0.4378 g of product (3_5) (38.0%). The infrared spectrum (Neat, NaCl) displayed absorption bands at 3060, 3005, 2985 (sh) , 1630 (br,w), 1550 (w) , 1415 (s), 1392, 1296, 1250 (s), 1226, 1212, 1130 (s), 1105 (sh) , 1080, 1024 (s), 980, 948 (s), 900, 861 (s), 790 (w) , 708, 670, 653, 611 cm""'-. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 144 (1.6), 143 (15.2), 115 (74.4), 96 (51.8), 95 (45.0), 75 (40.6), 68 (38.2), 66 (38.0) , 55 (48.6) , 39 (100.0) . Anal, for C-7lIgF20: C, 58.33; H, 4.20; F + 0, 37.47. Found: C, 58.45; H, 4.25; F + 0, 37.30 (diff). Preparation of the Phenyl Azide Adduct (3_6) of 3 , 3-dif luoro8-oxatricyclo[3.2.1.0^'^]oct-6-ene (35). In a 10 ml round bottom flask were placed 3 , 3-dif luoro-8-oxatricyclo[ 3 . 2 . 1 . 0^ ' ^ ] oct-6-ene (35^) (0.255 g, 1.77 mmol) in 3 ml of carbon tetrachloride. Phenyl azide (3j.) (0.6 g, 4.0 mmol) in 3 ml of carbon tetrachloride was added and the pale yellov/ solution was stirred (under nitrogen) magnetically at 50° C. Within 15 minutes, a white precipitate appeared, and after an additional 2 hours, the mixture was cooled and filtered, giving a yellow solid. The product was recrystallized from aqueous ethanol giving 0.0594 g (12.3%) fluffy white needles, mp 204 207 (decomposition) . Concentration of the filtrate gave an additional 0.210 g for a total yield of 0.269 g (55.6%). The infrared spectrum (KBr) displayed absorption

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Hi bands at 3062, 3000, 2919, 1598 (s), 1576 (sh) , 1499, 1475, 1440, 1359, 1273, 1260, 1250, 1232, 1217, 1182, 1151, 1137 (sh), 1113 (s,br), 1060, 1009, 981, 968 (sh), 953, 929, 910 (sh) , 903 (sh), 882, 839, 800, 748, 712 (w) , 698, 685, 660 (sh), 570 (w) , 540, 496, 460 (w) cm""'-. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 207 (6.0), 206 (25.0), 186 (22.6), 185 (8.2), 156 (15.0), 143 (9.0), 130 (13.4), 117 (16.6), 115 (6.0), 105 (5.9), 104 (54.1), 103 (6.4), 78 (8.8), 77 (100.0), 51 (31.8), 50 (5.0), 39 (12.0) . Anal. Calcd for C12HN3F2O: C, 59.31; H, 4.21; N, 15.96, F + 0, 20.52. Found: C, 59.47; H, 4.28; N, 15.91; F + 0, 20.34 (diff). Preparation of 2 , 4-dichloro-3 , 3-dif luoro-8-oxatricyclo[3.2.1.0 ' ]oct-6-ene ( 19a ) .^ In a sealed tube (FischerPorter) were placed 1, 2-dichloro-3 , 3-dif luorocyclopropene (lj4) (which had been passed through NaHC03 with CCI4, 2.20 g, 15.2 mmol) , 5 ml of carbon tetrachloride (Spectrar) , and an excess (5 ml) of furan. The tube was sealed and placed in an oil bath at 8 0° C for 24 hours. At this time, the tube was cooled, opened, the contents concentrated, and then percolated through a florex column with CH2CI2. Evaporation of the solvent left a yellowish oil, which upon distillation at reduced pressure, gave the colorless product 19a as a clear oil that became semisolid at 0° C. The yield was 2.03 g (63%), bp2^-75 ^^° ~ ^-^ ^'^^^ infrared spectrum (Neat,

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112 NaCl) displayed absorption bands at 3150, 3104, 3022, 1665 (w) , 1561 (w) , 1436 (s), 1420 (sh), 1400 {s,br), 1350, 1294 (sh), 1255 (sh) , 1238 (sh), 1221 (sh) , 1205' (s,br), 1114, 1086, 1049 (s), 1030 (s,br), 958, 922 (s) , 837 (s) , 792 (sh) , 782 (s) , 741 (s), 726, 678 (s) , 665 (sh) cm"^; 35 lit. (CCl^) : 3020 (m) , 1430, 1400, 1300, 1215, 1200, 1047, 1030, 920, 834, (780, 740, 722 liquid film), 674, 559 cm"^. Preparation of 2 , 4-dichloro-3 , 3-dif luoro-8-oxa tricyclo[3.2.1.0 ' joctane (37) . In a 50 ml round bottom flask equipped with a magnetic stirrer was placed 2 , 4-dichloro3,3-difluoro-8-oxatricyclo[3.2.1.0^''^]oct-6-ene ( 19a ) in 30 ml of absolute ethanol. Palladium-on-charcoal (10%, 0.050 gi was added and the mixture was stirred and cooled to 0° while a dry nitrogen cover was maintained. Then the flask was attached to a hydrogen reservoir, under slight positive pressure. The mixture was stirred under hydrogen for 24 hours at C, at which time an aliquot showed no vinyl "''H resonances in its nmr spectrum. The crude mixture was filtered, and the solvent was removed under reduced pressure to give 0.66 g (77%) of a white, crystalline solid, (37), 56 57.5 C. The infrared spectrum (KBr) displayed abmp sorption bands at 3030 (sh) , 3006, 2999 (sh) , 2962, 2920, 2880, 1543 (w) , 1468, 1430 (s,br), 1410 (s,br), 1389 (sh) , 1357, 1310 (s) , 1300 (sh) , 1290 (s), 1272, 1222 (s), 1210 (sh), 1196 (s), 1136, 1169 (sh) , 1041 (sh) , 1021 (s,br), 992 (sh), 936 (s) , 892 (s) , 830 (s), 812 (s), 771 (s), 679, 623 (s), 540 (s) , 450, 351 cm""^. The mass spectrum (70 eV)

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113 showed peaks at m/e (rel, intensity) 216 (0.1), 214 (0.2), 188 (8.5), 186 (14.5), 181 (4.0), 179 (11.4), 167 (38.0), 165 (41.4), 151 (100.0), 131 (45.4), 124 (52. 3), 115 (42.8) , 93 (43.6) , 75 (24.6) . Anal^. Calcd for C7H6CI2F2O: C, 39.10; H, 2.81; Cl, 32.98; F + 0, 25.11. Found: C, 39.13; H, 2.83; Cl, 32.87; F + 0, 25.17 (diff ) . Dechlorination of 2 , 4-dichloro-3 , 3-dif luoro-8-oxatricyclo274 ~~ [3.2.1.0 ] octane (32) . In a 3-necked, 50 ml round bottom flask equipped with a magnetic stirrer, a nitrogen inlet, and a reflux condenser were placed 2 , 4-dichloro-3 , 3-dif luoro8-oxatricYclo[3.2.1.o2/4]octane (0.357 g, 1.66 mmol) , 10 ml of dry tetrahydrofuran, and 2 ml of tert-butyl alcohol. Sodium metal (0.784 g, 0.034 gat.) was added, the system flushed with nitrogen, and the mixture stirred at 50° C under N2 for 32 hours. The yellow, cloudy mixture was coarsely filtered using an open Buchner funnel to remove large pieces of Na. A few drops of methanol were added to the solution, followed by pentane (50 ml) and water (100 ml) . The mixture was shaken in a separatory funnel to effect layer separation and the aqueous phase was extracted with an additional 50 ml of pentane. The pentane layers were combined, washed with 25 ml of saturated aqueous brine, dried, and the solvent removed under reduced pressure to give a yellow oil. Analysis by 'H nmr showed no starting material, and preparative 8'''pc (5', 3% SE-30, T^^i 95°, 30 cc He/min) gave a colorless oil, identical by IR spectroscopy to authentic 3 , 3-dif luoro-8-

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114 oxatricyclo[ 3 . 2 . 1 . ' joctane (34). Preparation of 2 , 4-dibromo-3 , 3-dif luoro-1 , 5-diphenyl[ 6 , 7 ] 2 4 benzo-8-oxatricyclo[ 3 . 2 . 1 . ' [oct-6-ene ( 38a ) . In a sealed tube (Fischer-Porter) were placed 3 , 3-dif luoro-1 , 2-dibromocyclopropene (1_5) (0.500 g, 2.14 mrnol) , 1, 3-diphenylisobenzofuran (0.577 g, 2.14 mmol) , and carbon tetrachloride (ca . 10 ml) . The tube was flushed with nitrogen, sealed, and placed in an oil bath at 80° C for 12 hours. The resulting pale yellow solution was evaporated to an orange oil, which was percolated through a florex column with methylene chloride. Evaporation of the solvent gave an off white solid, which was recrystallized from hexane, yielding 0.651 g (60.2%) of a white solid, mp 129° 130° C. The infrared spectrum (KBr) displayed absorption bands at 3060 (vw) , 1659 (w) , 1595 (w) , 1497, 1458, 1446 (m) , 1385 (s) , 1343 (s) , 1318 (w) , 1300 (s), 1272 (w) , 1200 (s) , 1170 (w) , 1156 (w) , 1100 (sh) , 1083 (w) , 1028 (w) , 1012 (sh) , 994, 980 (d,s), 904 (m) , 853 (w) , 833 (s), 776 (s) , 765 (s), 750 (s), 720 (w) , 695 (sh) , 690 (s), 589 (m) , 540 (m) cm" . The mass spectrum (70 eV) shov/ed peaks at m/e (rel. intensity) 505 (1), 504 (1), 503 (2), 502 (1), 489 (1), 487 (2), 485 (1), 426 (13.6), 424 (13.6), 384 (4.2), 382 (8.1), 380 (4.4), 345 (13.0), 287 (19.4), 271 (19.5), 240 (7.7), 239 (9.3), 210 (47.3), 166 (5.8), 153 (8.7), 105 (100.0), 77 (47.3). Anal. Calcd for C23lii4Br2F20 : C, 54.79; H, 2.80; Br, 31.70; F + 0, 10.71. Found: C, 55.01; H, 2.90; Br, 31.54; F 40, 10.55 (diff)

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115 Preparation of 3 , 3-dif luoro-1 , 5-diphenyl[ 6 , 7 ] -benzo-8oxatricyclo[3.2.1.0^'^]oct-6-ene (39_) . A mixture of 2,4dibromo-3 , 3-dif luoro-1 , 5-diphenyl[6,7] -benzo-8-oxatricyclo[3.2.1.0^'^]oct-6-ene (38a) (2.52 g, 5.00 mmol) , tri-nbutyltin hydride (5.82 g, 20.0 mmol) , and 3 drops of ditert-butyl peroxide was placed in a sealed tube (FischerPorter) and heated at 100° C for 24 hours. The resulting clear orange oil was chromatographed on alumina (80 2 00 mesh) , using hexane to separate the mixture of alkyltin residues and the product. The product fractions were evaporated and recrystallized from hexane to give 0.523 g (30%) of white crystals (3_9) , mp = 115° 116° C. The infrared spectrum (KBr) displayed absorption bands at 3050 (br) , 1595 1595 (w,br) , 1490, 1455 (sh) , 1443, 1410 (br,s), 1340 (s) , 1315 (sh) , 1299 (w) , 1249 (s) , 1227 (m) , 1175 (w) , 1150, 1127 (s) , 1103 (w) , 1080, 1050 (sh), 1040, 1020 (w) , 990 (br,s), 962 (s) , 950, 910 (w) , 893 (w) , 867 (s), 835, 807, 790 (w) , 765 (s), 748 (s), 693 (s), 679 (s), 660 (sh) , 650 (m) , 560 (m) , 523 (m) , 480 (w) , 410 (w) cm~^. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 347 (14.1), 346 (51.3), 345 (12.2), 327 (14.6), 326 (7.8), 282 (7.0), 281 (26.9), 280 (6.7), 271 (10.0), 270 (7.6), 249 (19.5), 222 (41.7), 202 (28.4), 192 (19.5), 165 (7.3), 105 (100.0) , 77 (29.5) . Anal. Calcd for C:23H-^gF20: C, 79.75; H, 4.66; F + 0, 15.59. Found: C, 79.61; H, 4.74; F + 0, 15.65 (diff ) .

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116 Preparation of 2 , 4-dibromo-3 , 3-dif luoro[ 6 , 7 ] -benzo-8oxatricyclo[3.2.1.0^''^]oct-6-ene (4_0) .^^ 1 , 4-Bis (2-pyridil) tetrazine (3.69 g, 14.2 mmol) was dissolved in 50 ml of methylene chloride in a 3-necked round bottom flask (250 ml) equipped with a dropping funnel, condenser, magnetic stirrer and nitrogen inlet. The resulting deep red solution was stirred and chilled to 0° C under nitrogen. 1,2-Dibromo3,3-difluorocyclopropene (15) (3.32 g, 14.2 mmol) and 1,4dihydronaphthalene-1 , 4endo -oxide (2.05 g, 14.2 mmol) in 50 ml of methylene chloride was added dropwise over a period of an hour. The mixture was stirred for an additional hour, while a small excess of the 1 , 4-dihydronaphthalene-l , 4-endooxide was added in methylene chloride to complete decolorization of the solution. The resulting pale yellow solution was evaporated and the resulting yellow solid was chromatographed on alumina (MCB 80-200 mesh) using benzene as elutant. The benzene solution was evaporated and the resulting white solid recrystallized from aqueous ethanol to give 3.62 g (72%) of 40_ as a white crystalline solid, mp 108° 109° C. The infrared spectrum (KBr) displayed absorption bands at 3040, 3000, 1460, 1413 (s), 1392 (s), 1365, 1340, 1276 (w) , 1265 (sh) , 1220, 1203 (s), 1150, 1087, 1048, 1017, 998 (s), 984 (s) , 922 (m) , 896 (w) , 860 (s), 814 (s), 766 (sh), 750 (s), 696 (m) , 654 cm . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 354 (0.2), 352 (0.4), 350 (0.2), 325 (0.4), 323 (0.8), 321 (0.4), 306 (10.2), 304 (22.1), 302 (11.8), 273 (6.8), 271 (7.1), 245 (17.6), 244 (13.8), 243

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117 (17.8), 242 (12.8), 192 (20.0), 164 (100.0), 144 (11.8), 143 (10.5), 82 (14.7), 80 (15.1), 63 (12.8), 56 (16.7), 40 (74.0). Anal. Calcd for C3_iH5Br2F20 : C, 37.53; H, 1.72; Br, 45.41; F + 0, 15.34. Found: C, 37.47; H, 1.77; Br, 45.33; F + 0, 15.43 (diff ) . Preparation of 3 , 3-dif luoro[6,7] -benzo-8-oxatricyclo[3.2.1.02>^]oct-6-ene (41). A mixture of 2 , 4-dibromo-3 , 3dif luoro[6,7] -benzo-8-oxatricyclo [3.2.1.0^''*] oct-6-ene ( 40 ) (1.056 g, 3.00 miriol) , tri -n-butyltin hydride (3.49 g, 12.0 mmol) , and a few drops of ditert -butyl peroxide wore placed in a sealed tube (Fischer-Porter) and heated at 90° C for 24 hours. The resulting mixture was chromatographed on alumina (MCE 80-200) . After elution of the alkyltin residues with hexane , the product was eluted with 1:1 benzene:hexane. Evaporation of the solvent and recrystallization of the residue from aqueous ethanol afforded 0.26 g (46%) of 4j^ as a fluffy white solid, mp = 88.5° 89.0° C. The infrared spectrum (KBr) displayed absorption bands at 3076, 3036, 1600 (w,br), 1460 (sh) , 1421 (s) , 1370 (w) , 1346 (w) , 1289 (m) , 1260 (sh), 1251 (s), 1222 (m) , 1207, 1189, 1155 (w) , 1133 (s) , 1119 (m) , 1099 (w) , 1052 (s), 1015 (w) , 996 (s), 990 (sh), 952 (m) , 931 (s), 868 (s), 830 (s), 756 (s), 670 (s) cm . The mass spectrum (7 eV) showed peaks at m/e (rel. intensity) 195 (0.34), 194 (2.4), 193 (2.2), 174 (1.1), 173 (1.2), 147 (15.2), 146 (47.2), 145 (8.2), 115 (52.7), 89 (41.7), 87 (38.3), 73 (100.0), 43 (89.0), 19 (86.3).

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118 Anal. Calcd for C^^HgT^O: C, 68.04; H, 4.15; F + 27.81. Found: C, 68.20; H, 4.22; F + 0, 27.58 (diff). Reaction of 3 , 3-dif luoro[ 6 , 7 ]-benzo-8-oxatricyclo [3.2.1.0^'"^]oct-6-ene (41) with Triphenylphosphine D ibromide. ^^ A 3necked 50 ml round bottom flask was equipped with a 25 ml addition funnel, a reflux condenser, a magnetic stirrer and a thermometer. The system was flushed with and a cover of nitrogen v/as maintained throughout the reaction. In the flask were placed triphenylphosphine (0.92 g, 3.5 mmol) and chlorobenzene (5 ml) . The resulting solution was stirred and cooled to C. A solution of bromine (0.56 g, 3.5 mmol) in chlorobenzene (5 ml) was placed in the addition funnel and added to the flask at such a rate that the temperature was below 5 C. A yellow precipitate (0 PBr'''Br~) quickly formed. At that time, the mixture was heated to a bath temperature of 100° C, and 3 , 3-dif luoro[ 6 , 7 ] -benzo-82 4 oxatricyclo[3.2.1.0 ' ]oct-6-ene (4J^) (0.500 g, 2.6 mmol) in chlorobenzene was added. The mixture was stirred and heated at 100 C for 5 hours, at which time an nmr spectrum of the crude mixture showed no starting material remained. Chromatographed on silica gel with benzene, evaporation of elutant and recrystallization of the crude residue from aqueous ethanol gave 0.387 g of a brown solid (57.9%) which by nmr was contaminated with triphenylphosphine residues. Additional purification by chromatography on silica gel with hexane gave a white solid, mp 63 64°, which was identified as B-

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119 (Fluorodibromomethyl) -Naphthalene (4^). The infrared spectrum (KBr) displayed absorption bands at 3040 (w) , 1789, 1624 (w) , 1599 (w) , 1500 (w) , 1466 (w) , 1384 (w) , 1352, 1280 (s) , 1265 (sh), 1229, 1190, 1161 (w) , 1114 (s) , 1050 (s) , 1019 (sh), 966 (sh) , 950 (s) , 914, 891 (s) , 860, 792 (s), 767, 746 (w) , 610 (w) cm"!. The calculated mass for [M]t is 257.9678 and 255.9712, while accurate mass determination gave 257.9687 and 255.9698, for errors of +3.1 ppm and -1.4 ppm. UV (cyclohexane) : Xmax (e); 212 (sh) (1.6 X 10^), 228 (3.2 x 10^), and 274 (8.2 x 10^). Preparation of 2-methoxy-l , 6-dibromo-7 , 7-dif luorobicyclo[4.1. Olhept-3-ene (46) . In a sealed tube (Fischer-Porter) were placed 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15) (1.99 g, 8.5 mmol, freshly distilled and passed through a NaHC03 plug in a micropipet) , 20 ml of carbon tetrachloride (Spectrar) , and l-methoxy-l,3-butadiene (5.0 g, 59.5 mmol, Aldrich) . The tube was sealed and placed in an oil bath at 115° C. The colorless solution gradually darkened, and after fourteen hours, the mixture was black-red. The tube was then cooled, and the contents were rinsed into a round bottom flask with methylene chloride. Evaporation of the solvents left a black oil, which was chroma tographed on a basic alumina. The first 100 ml hexane fraction contained no product. Two 250 ml benzene fractions were collected, and evaporated to yield 1.31 g (48.4%) of 4_6 as a yellow oil. The infrared spectrum (Meat, NaCl) displayed absorption bands at 3042, 2998, 2932, 2905,

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120 2880 (sh), 2825, 1669, 1465 (sh), 1450 (sh), 1442 (s), 1412 (s) , 1387, 1340, 1319, 1290, 1209 (s), 1195 (sh), 1155, 1089 (sh) , 1047, 990 (sh), 978 (w) , 970 (w,sh), 951, 902, 889, 770, 760, 732, 693, 630 (w) cm"^. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 318 (0.1), 316 (0.2), 314 (0.1), 239 (7.1), 237 (8.7), 207 (25.0), 205 (23.9), 127 (51.3), 81 (100). Anal. Calcd for C8H8Br2F20: C, 30.22; II, 2.54; Br, 50.26; F + 0, 16.98. Found: C, 30.42; II, 2.62; Br, 50.11; F + 0, 16.85 (diff ) . Preparation of 2-methoxy-7 , 7-dif luorobicyclo [ 4 . l,0]hept-3ene (47) . In a 10 ml round bottom flask equipped with a magnetic stirrer wore placed, at 0° C, 2-methoxy-l , 6-dibromo7,7-difluorobicyclo[4.1.0]hept-3-ene (4_6) (1.67 g, 5.25 mmol) tri-n-butyltin hydride (4.58 g, 15.75 irnnol), and one drop of di-tert-butyl peroxide. The flask was tightly stoppered, and the mixture was stirred and heated at 50° C for 70 hours. The flask was then cooled to room temperature, opened, and attached to an assembly for bulb to bulb distillation. The reaction mixture was frozen with liquid nitrogen, and the system was evacuated and sealed off. The receiver flask was cooled with a dry-ice/isopropyl alcohol bath. Upon warming to room temperature and gentle heating, a clear, colorless oil distilled. Analysis by H nmr indicated only product and some alkyltin residues (yield of crude material 0.911 g, 0.840 g theoretical yield) . An ethereal solution of the

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121 product mixture was separated by preparative glpc (5', 3% SE-30 column, T^^^ = 70° C, T^^^ = 120° C, 30 cc He/min). The yield of 4_7 as a clear colorless oil was 0.3558 g (42.4%, low due to partially plugged injection port). The infrared spectrum (Neat, NaCl) displayed absorption bands at 3039, 2982, 2934, 2903, 2822, 2812, 1663, 1469 (s), 1436, 1398, 1347, 1330 (w) , 1306 (w) , 1284 (s), 1235 (sh), 1211, 1191, 1150 (s), 1127 (w) , 1110 (sh), 1088 (s), 1070 (sh) , 1023, 970, 930 (sh), 900, 819, 712, 695, 625 (sh), 616 cm"^. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 160 (6.1), 159 (7.5), 145 (14.4), 132 (28.1), 128 (12.2), 127 (38.2), 110 (20.5), 109 (100.0). Anal . Calcd for CgH^QF20: C, 59.99; H, 6.29; F + 0, 33.72. Found: C, 59.90; H, 6.33; F + 0, 33.69 (diff). A trace of a second minor component was also isolated from the gas chromatography and was identified by H and F nmr and G.C. mass spectral analysis to be 41_ and l-bromo-5methoxy-7, 7-difluorobicyclo[4.1.0]hept-3-ene (48) (ca. 1:1). The mass spectrum (70 eV) of the latter showed peaks at m/e (rel. intensity) 159 (18.0), 131 (14.8), 127 (33.0), 109 (10.6), 81 (15.5), 77 (25.0), 63 (100.0). Preparation of 2 , 4-dibrorao-3 , 3-dif luoro-8(diphenylmethylene) 2 4 tricyclo[3. 2.1. ' ]oct-6-ene ( 51a ) . Diphenylfulvene (4.60 g, 20.0 mmol) , 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15_) (5.68 g, 20.0 mmol), and ca. 40 ml of carbon tetrachloride (Spectrar) were placed in a sealed tube (Fischer-Porter) and heated at

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122 120 C for 15 hours. The tube was then cooled, opened, the solvent removed, and the dark residue chromatographed on a Florex column (1" x 10") with pentane. The pentane was evaporated leaving an orange oil, which, when dissolved in a minimum amount of hot hexane , afforded 6.41 g (69%) of (51a) as an off-white solid, mp 153° 155° C. The infrared spectrum (KBr) displayed absorption bands at 3082 (w) , 3050 (w) , 3017 (w) , 2990 (sh), 1597, 1490, 1442, 1392, 1379 (broad d) , 1315, 1295 (broad d,w), 1234 (w) , 1220 (sh), 1192 (s) , 1155, 1092 (w) , 1072, 1012, 974 (s), 829, 780, 770, 748, 721, 711 (sh) , 700 (s) , 669 (sh), 660, 620, 610 (sh) cm~^. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 466 (8.3), 464 (15.8), 462 (8.3), 446 (0.12), 444 (0.17), 442 (0.10), 386 (71.9), 385 (18.7), 384 (73.8), 383 (22.5), 366 (5.8), 365 (21.7), 364 (6.8), 363 (22.8), 305 (100), 304 (65.6), 285 (63.5), 284 (72.6), 252 (28.7), 227 (31.2), 207 (26.8), 191 (69.0), 165 (42,4), 126 (39.4), 109 (20.0). Anal. Calcd for C2iH3_4Br2F2 : C, 54.34; H, 3.04; Br, 34.44; F, 8.19. Found: C, 54.40; 11, 3.12; Br, 34.39; F, 8.09 (diff). Prepa ration of 2 , 4-dibromo-3 , 3-dif luoro-8(diphenylmethylene) tricyclo[3.2.1.0^''^]octane (52a) . In a 3 00 ml round bottom flask equipped with a magnetic stirrer and a reflux condenser were placed 2 , 4-dibromo-3 , 3-dif luoro-8(diphenylmethylene) tricyclo[3.2.1.0^'^]oct-6-ene (5_la) (2.50 g, 5.40 mmol) , ptoluenesulfonyl-hydrazine (5.03 g, 27.0 mmol), diglyme (150 ml) , and triethylamine (5 ml) . The mixture was stirred under

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123 o a nitrogen atmosphere and heated at 8 0° C for 24 hours. The resulting orange solution was poured into an equal volume f pentane. A small oily brown layer settled and was drained off. The pentane solution was washed successively with 5% H2SO4, 5% NaOH, and saturated aqueous NaCl . After drying (Na2S04) and removal of solvent in vaccuo, the orangeyellow solid was recrystallized from hexane to yield 1.48 g (58.8%) of 5_2a as off white crystals, mp 119.5° 120.5° C. The infrared spectrum (KBr) displayed absorption bands at 3080, 3050, 3020, 2999, 2970, 2943, 2870, 1975 (w) , 1803 (w) , 1590 (m) , 1482, 1437, 1402 (s) , 1385 (sh) , 1315 (w) , 1290 (w) , 1258 (m) , 1197 (s), 1180 (sh), 1145 (m) , 1124 (m) , 1105 (m) , 1060 (m) , 1043 (m) , 1022 (m) , 986 (m) , 959 (s) , 820 (m,s), 769 (sharp, m) , 739, 711 (m) , 692 (s), 651 (w) , 620 (w) , 600 (w) , 580 (w) , 522 (m) , 460 (w) , 448 (w) cm""'-. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 468 (13.8), 466 (28.3), 464 (14.1), 440 (1.6), 438 (2.6), 436 (1.7), 388 (11.6), 387 (38.2), 386 (14.6), 385 (38.5), 307 (54.5), 306 (100.0), 286 (26.2), 278 (20.2), 217 (26.8), 191 (34.5), 143 (21.6), 91 (16.8). Anal. Calcd for C H Br F : C , 54 . 10 ; H, 3 . 46 ; Br, 34.29; F, 8.15. Found: C, 54.15; II, 3.54; Br, 34.10; F, 8.21 (diff). Preparation of 3 , 3-dif luoro-8(diphenylmethylene) -tricyclo[3.2.1.0.^''^]octane (53a). 2 , 4-Dibromo-3 , 3-dif luoro-8(diphenylmethylene) -tricyclo[3 . 2 . 1 . 0^ '4]octane ( 52a ) (0.756 g, 1.63 mmol) , tri-n-butyltin hydride (1.43 g, 4.91 mmol) ,

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124 and 3 drops of ditert -butyl peroxide were placed in a sealed tube (Fischer-Porter) and heated at 90° C for 24 hours. The resulting clear yellov; oil was chromatographed on alumina (MCB 80-200). The first fraction (pentane) contained only alkyl-tin residues (by nmr) . The second fraction (benzene) upon evaporation gave a pale yellow oil, which crystallized on standing. Recrystallization from ethanolwater gave 0.116 g (23%) of 53a as a white solid, mp 79.5° 80.5° C. The infrared spectrum (KBr) displayed absorption bands at 3056, 3000, 2978, 2930, 2915, 2880, 2850, 1592 (m) , 1485, 1438 (s) , 1410 (sh), 1315 (w) , 1297 (m) , 1272 (m) , 1242 (s) , 1180 (w) , 1155 (w) , 1129 (m) , 1109 (s), 1061 (m) , 1020 (m) , 940, 922 (d) , 895 (w) , 870 (w) , 850 (w) , 777 (w,sh), 767 (m) , 749 (m) , 720 (m) , 696 (s) , 620 (w) , 602 (w) cm"l. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 310 (2.5), 309 (21.2), 308 (100.0), 290 (3.8), 289 (7.3), 261 (11.3), 260 (20.4), 259 (13.4), 231 (31.6), 180 (26.9), 165 (35.6), 150 (29.0), 91 (17.6), 77 (15.6). Anal . Calcd for C2iH2^3F2: C, 81.79; H, 5.88; F, 12.32. Found: C, 81.87; H, 5.93; F, 12.20. Preparation of 2 , 4-dibromo-3 , 3-dif luoro-8-dimethylmethylene) tricyclol^3.2.1.0 ' ]oct-6-ene ( 51b ) . Dimethylfulvene (3.19 g, 30.0 mmol, Frinton) , 1 , 2-dibromo-3 , 3-dif luorocyclopropene ( 15 ) (3.52 g, 15.0 minol) , and 50 ml of carbon tetrachloride were placed in a sealed tube (Fischer-Porter) and heated at 115 C for 12 hours. The resulting dark brown solution was evaporated, and the oily residue was chromatographed on Florex,

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125 and eluted with pentane. Evaporation of the pentane gave (51b) as a yellow iol (3.10 g, 60%). This oil, which was unstable, was inmediately reduced. Preparation of 2 , 4-dib romo-3 , 3-dif luoro-8(dimethylmethylene) tricyclo[3.2.1.o2/4]og^-^^3 (32b) . In a 300 ml round bottom flask equipped with a magnetic stirrer and a reflux condenser were placed 2 , 4-dibromo-3 , 3-dif luoro-8(dimethylmethylene) hydrazine (25.6 g, 138 mmol) , 1 , 2-dimethoxyethane (200 ml), and triethylamine (25 ml) . The mixture was stirred under a nitrogen atmosphere and heated at 8 0° C for 8 hours. The resulting orange solution was cooled and poured into 300 ml of pentane. A small oily layer settled and was drained off and discarded. The pentane solution was washed successively with 5% H2SO4, 5% NaOH, and saturated aqueous brine. After drying (Na2S04) and removal of solvent, the remaining oil was chromatographed on florex using pentane (200 ml) as elutant. Evaporation of solvent and recrystallization from hexane gave 0.793 g (17%) of 52b as white crystals, mp 82° 85° C. The infrared spectrum (KBr) displayed absorption bands at 2980, 2960, 2920, 2900, 2865, 2840 (sh), 1720 (w) , 1465 (sh), 1443, 1413 (s) , 1390, 1373, 1295, 1270, 1250 (w) , 1200 (s), 1170, 1143 (w) , 1115 (w) , 1105 (w) , 1052, 992, 962 (s), 872 (w) , 841 (s), 790 (sh) , 742 (s), 702 cm~^ . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 344 (3.1), 342 (6. 9), 340 (3.5), 317 (3.0), 315 (5.8), 313 (2.9), 296 (3.9), 294 (7.3), 292 (3.9), 282 (0.6), 280 (0.9), 278 (0.5), 263 (22.9), 261 (23.0), 235 (92.9), 233 (100), 218 (18.6), 216 (18.6), 183

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126 (22.8), 167 (18.0), 154 (30.8), 41 (63.2), 39 (31.0), 27 (21.6) . Anal . Calcd for C]_iH2^2Br2F2 : C, 38.62; H, 3.54; Br, 46.73; F, 11.11. Found: C, 38.78; H, 3.67; Br, 46.59; F, 11.06 (diff ) . Preparation of 3 , 3-dif luoro-8(dimethylmethylene) tricyclo[3.2.1.o2''5]octane 5^). 2 , 4-Dibromo-3 , 3-dif luoro-8(dimethylmethylene) tricyclo[3 .2.1. 0^ '4] octane ( 52b ) (0.342 g, 1.00 mmol) , tri-n-butyltin hydride (0.873 g, 3.00 mmol) , and a few drips of ditert butyl peroxide were placed in a sealed tube (Fischer-Porter) and heated at 90° for 24 hours. The resulting reaction mixture was chromatographed on alumina (MCB 80-200). After elution with 30 ml of pentane, the following five fractions (15 ml) were combined and evaporated. The residue was purified by preparative glpc (5', 3% SE-30, Tcol = 103° C, 30 psi) to give 0.102 g (56%) of 53b as a white crystalline solid, mp = 58.5° 59.5° C. The infrared spectrum (KBr) displayed absorption bands at 3047, 2987, 2967, 2946, 2907, 2867, 1439 (s,br), 1363, 1327 (w) , 1297, 1278, 1252, 1177 (w) , 1142 (sh) , 1117 (s,br), 1092 (sh) , 1062 (w) , 1022, 996, 980 (sh), 926 (br) , 876 (sh) , 862, 832 (sh) , 796 (w) , 705, 635 (w) cm"-^ . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 184 (0.55), 182 (0.68), 165 (5.2), 150 (24.6), 136 (100), 135 (55.8), 121 (67.5), 110 (26.5), 101 (35.5), 96 (23.5), 75 (14.4), 39 (17.8) , 27 (48.8) , 26 (40.6) .

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127 Anal . Calcd for C-^jll-^^F^: C, 71.71; H, 7.66; F, 20.63. Found: C, 71.46; H, 71.74; F, 20.80 (diff ) . Preparation of Spiro[ 4 . 2 ] heptadiene (56). In a 11 3-necked Morton flask equipped with a paddle blade stirrer, a dry ice/ isopropyl alcohol condenser, and a 250 ml dropping funnel with a gas inlet tube was condensed 400 ml NH.^, with the aid of a dry ice/isopropyl alcohol bath under the flask. At -70° C, with stirring, Na (11.5 g, 0.500 gat.), in small pieces, was added, resulting in a characteristic deep blue solution. The mixture was stirred at -70° C for 2.75 hours, after which time no Na pieces were seen. Then, still at -70° C, freshly distilled cyclopentadiene (44 g, 0.66 mol) was added dropwise over a period of 35 minutes, after which the blue color slowly faded. When the mixture was pale yellow, ethylene dibromide (94 g, 0.50 mol) was added dropwise at -70 C over 2 hours, resulting in a yellow solution that after stirring at -70° c for 5 hours became green, with the appearance of a yellow precipitate. At this point, most of the NH3 was allowed to evaporate and ether (250 ml) was added, giving a brown solution. The mixture was filtered and the etheral solution to which 25 ml methanol had been added was carefully washed with water (2 x 2 00 ml) , and dried giving an orange solution. Evaporation of the solvent and distillation gave 35.1 g of a colorless liquid, bpjLOO ^^° 59 C, lit. bp-j^QQ 57 , which by nmr analysis contained abc 23.4 g (50.9%) of spiro 4.2 heptadiene (56) contaminated

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12) with ethylene dibroraide . For storage purposes, the distilled material was diluted with carbon tetrachloride (1:1, w:w) and stored at 0° C. Preparation of 2 , 4-dibromo -3 , 3-dif luorotricyclo [3.2.1.0^'^]oct-6-ene8-spiro -cyclopropane (57a) . Spiro 4.2 hepta1,3-diene (5_6) (0.736 g, 8.00 mmol) in carbon tetrachloride (2 ml) was added to a carbon tetrachloride (2 ml) solution of l,2-dibromo-3, 3-dif luorocyclopropene (15_) (0.887 g, 3.79 mmol) containing a trace of NaHC03 . The solution was chilled (0° C) and magnetically stirred during the addition. The 10 ml round bottom flask containing the pale yellow solution was then attached to a reflux condenser with a nitrogen bubbler and the mixture was heated to 50° and stirred. When the II nmr of the reaction mixture showed a constant ratio of product to diene vinyl absorptions (after 4 days), the mixture was cooled and excess diene and solvent were removed at room temperature using a vacuum pump. The resulting Ixght orange oil was chromatographed on a neutral alumina (MCB 80-200) with benzene, then the pale yellow oil was rechromatographed on silica gel with pentane yielding 0.60 g (49%) of SJa. as a colorless oil. The infrared spectrum (Neat, NaCl) displayed absorption bands at 3060, 2980, 2950 (sh), 2910 (w) , 2860 (sh), 1649 (m) , 1477 (w) , 1450 (w) , 1430 (w) , 1415 (m) , 1390 (sh), 1378 (vs) , 1309 (s), 1329 (m) , 1299 (s) , 1289 (sh), 1244 (w) , 1208 (sh) , 1192 (s), 1185 (s), 1159 (s) , 1114 (m) , 1090 (sh) , 1079 (m) , 1052 (w) , 1028 (s), 1018 (sh).

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129 1000 (m) , 984 (m) , 962 (s) , 931 (m) , 915 (sh) , 896 (w) , 886 (w) , 860 (sh) , 856 (m) , 809 (w) , 790 (m) , 764 (s), 738 (s) , 719 (m) , 686 (w) , 660 (m) cm"!. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 328 (2.0, 326 (4.0), 324 (2.1), 300 (0.47), 298 (0.96), 296 (0.51), 247 (37.1), 245 (38.0), 219 (12.3), 217 (12.2), 166 (100.0), 146 (77.8), 138 (34.5), 91 (32.6), 51 (41.5). Anal . Calcd for CioH8Br2F2= C' 36.84; H, 2.47; Br, 49.03; F, 11.66. Found: C, 37.02; H, 2.48; Br, 48.89; F, 11.61 (diff ) . Preparation of 3 , 3-dif luorotricyclo [ 3 . 2 . 1 . 0^ ' '^ ] oct-6-ene 8spiro -cyclopropane ( 58a ) . In a 10 ml round bottom flask eqiupped with a magnetic stirrer were placed (with ice bath cooling) 2 , 4-dibromo-3 , 3-dif luorotricyclo[ 3 . 2 . 1 . 0^ ' 4] q^.^.. 6-ene8-spiro -cyclopropane ( 57a ) (1.78 g, 5.46 mmol) , trin-butyltin hydride (4.72 g, 16.2 mmol), and one drop of ditert -butyl peroxide. The flask was tightly stoppered and the mixture was stirred and heated at 60° c for twenty hours. The flask was cooled before opening, and was attached to a short path distillation apparatus. The receiver flask was cooled in a dry ice-isopropyl alcohol bath, and bulb to bulb distillation of the reaction mixture gave 0.447 g of a colorless oil, fairly pure by 'H nmr. Final purification was best effected by preparative glpc (5' x 1/4" 15% PMPE, T^Qj 100° c, 30 cc He/min) , and gave 0.332 g (36%) of 58a . The infrared spectrum (Neat, NaCl) displayed absorption

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130 bands at 3117, 3070, 3060, 3027, 2990, 2979, 2921, 1672 (m) , 1551 (w) , 1460 (w) , 1430 (s), 1412 (s) , 1363, 1350 (sh) , 1330 (sh) , 1310, 1264 (s), 1210 (sh), 1196 (sh),1189, 1136 (w) , 1107 (s) , 1086, 1054, 1025, 1000, 980 (w) , 961, 942 (s) , 912 (w,sh), 907, 867, 834 (w) , 813 (w) , 792 (w) , 781 (w) , 769 (w,sh), 740 (w) , 712, 659 (s) cm-1. The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 168 (9.5), 167 (10.5), 153 (66.5), 140 (100), 133 (43.1), 91 (89.2) , 78 (62.7) , 51 (41.5) , 39 (57.6) . Anal. Calcd for C10H10F2 = C, 71.41; H, 5.99; F, 22.59. Found: C, 71.58; H, 6.03; F, 22.39 (diff ) . Preparation of 2 , 4-dib romo-3 , 3-dif luorotricyclo [3.2.1.0^''^]oct-6-ene (63) . In a 25-ml, 3-necked round bottom flask equipped with a nitrogen inlet and a magnetic stirrer was placed l,2-dibromo-3, 3-dif luorocyclopropene (1_5) (2.18 g, 9.32 mmol) in about 5 ml of carbon tetrachloride with a few crystals of NaHC03. The mixture was stirred under nitrogen at 0° C and an excess (2 ml) of freshly distilled cyclopentadiene was added. The resulting solution was stirred at room temperature and the reaction was followed by gas chromatography (5', 20% SE-30, T^^i = 100°). After three days, the reaction mixture was transferred to a one-necked flask which was placed on a rotary evaporator. Removal of excess cyclopentadiene and nmr spectral analysis showed the 1:1 adduct to be present. The crude reaction mixture was percolated through florex (with pentane) and the resulting

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131 solution evaporated to give a colorless oil which yielded two fractions upon vacuum distillation: fraction one (bp3o_5o 80 90 ) cyclopentadiene dimer; fraction two (bp2 75 88° 90°) pure product 63_. The infrared spectrum (Neat, NaCl) displayed absorption bands at 3025, 2980, 2918, 1650 (w) , 1620 (sh), 1555 (w) , 1467, 1435 (sh), 1370 (s), 1340 (sh), 1307, 1255 (sh), 1239, 1212, 1172 (s), 1130 (sh), 1094 (w) , 1049 (s), 1010, 989, 948 (s) , 825 (sh), 910 (sh) , 900 (sh) , 879 (w), 932 (w), 809 (s), 802 (sh), 730 (s), 715 (sh), 664 (s), 610 (sh) cm" . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 302 (1.5), 300 (3.2), 298 (1.6), 114 (19.8) , 75 (6.0) , 63 (12.6) . Anal. Calcd for CgngBr2F2 : C, 32.03; H, 2.02; Br, 53.28; F, 12.67. Found: C, 32.08; H, 2.03; Br, 53.16; F, 12.72 (diff ) . Preparation of 3 , 3-dif luorotricyclo f 3 . 2 . 1 . 0^ ' '^ loct-6-ene (64). In a 10 ml round bottom flask equipped with a magnetic stirrer were placed 2 , 4-dibromo-3 , 3-dif luorotricyclo [3.2.1.0^''^] oct-6ene (6_3) (3.6 g, 12.0 mmol) , tri-n-butyltin hydride (with ice bath cooling, 7.0 g, 24.0 ramol), and ditert -butyl peroxide (one drop) . The flask was stoppered and the mixture was stirred and heated at 50° for 24 hours. Bulb to bulb distillation of the volatiles gave 0.709 g (41%) of crude product 6_4, which was purified by preparative glpc (5', 5% SE-30, ^col ^~' ^' 20 cc He/min) . The infrared spectrum (Neat, NaCl) displayed absorption bands at 3109, 3063, 3030, 2982, 2919,

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i J/' 1625 (w) , 1569 (w) , 1556 (m) , 1474, 1421 (s) , 1409 (s), 1392, 1314, 1270 (sh), 1258 (s), 1220 (w) , 1182 (w) , 1120 (s), 1056, 1029, 979, 950, 921, 882 (w) , 861, 805 (m) , 738 (sh) , 713, 662 cm . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 142 (59.7), 141 (31.0), 127 (53.9), 122 (12.0), 121 (14.5), 91 (90.0), 78 (73.4), 77 (100.0), 65 (23.4) , 51 (33.5) , 40 (62.6) . Anal. Calcd for CgHgF2: C, 67.59; H, 5.67; F, 26.73. Found: C, 67.69; H, 5.69; F, 26.72 (dif f ) . Preparation of 2 , 4-dibromo-3 , 3-dif luorotricycl o [ 3 . 2 . 1 . 0^ ' "^ ] octane (65) . The crude reaction mixture from a preparation of 2,4-dibromo-3,3-difluorotricyclo[3.2.1.0^''^]oct-6-ene (63) was dissolved in a minimal amount of benzene and 5 ml absolute ethanol, and 50 mg 10% Pd-on-carbon was added. The dark brown mixture was stirred vigorously (magnetic stirring) under an atmosphere of E^ (excess) overnight at room temperature. Nmr spectral analysis showed no vinyl protons, so the reaction mixture was filtered and percolated through a column of florex with pentane as solvent. The pentane was evaporated, and the residue was analyzed by gas chromatography (5', 3% SE-30, '^col 1*^2 C) . The third component was isolated on preparative scale affording 6_5 as a colorless oil (1.0292 g, 36.6% based on starting cyclopropene) . The infrared spectrum (Meat, NaCl) displayed absorption bands at 3030 (w) , 2970 (s) , 2940 (sh) , 2910 (sh) , 2875, 1665 (impurity), 1485 (w) , 1460 (w) , 1445 (w) , 1402 (s), 1334 (m) , 1309 (w) , 1294, 1279, 1255 (w) , 1244 (w) , 1200 (s) , 1170 (s), 1132 (w) , 1098 (w) , 1080 (w) , 1062

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133 (s) , 1053 (sh) , 1038 (w) , 1021, 995 (w) , 982 (sh) , 964 (s), 939 (s) , 920 (sh), 890 (w) , 871 (v/) , 805 (w) , 705 (w) , 751 (w) , 739 (s) , 712 (w,sh), 702 (w) cm~^.' The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 304 (0.3), 302 (0.9), 300 (0.8), 298 (0.3), 276 (0.4), 274 (0.7), 272 (0.4), 223 (51.8), 221 (60.4), 195 (50.6), 193 (52.8), 115 (100), 63 (17.2), 44 (28.3), 39 (52.0), 32 (50.9) . Anal . Calcd for CgHgBr2F2: C, 31.82; H, 2.67; Br, 52.93; F, 12.58. Found: C, 31.84; H, 2.65; Br, 52.75; F, 12.66 (diff) . Preparation of 3 , 3-dif luorotricyclo[ 3 . 2 . 1 . 0^ ' '^ ] octane (66). 2,4-Dibromo-3,3-dif luorotricyclo[3 .2.1. 0^'^] octane (65) (0.72 g, 2.4 mmol), tri-n-butyltin hydride (excess, about 2 g) , and a few drops of di-tert-butyl peroxide were placed in a 25 ml round bottom flask and heated at 70° C overnight under nitrogen. The flask was then attached to a short path distillation apparatus. A bulb to bulb distillation under vacuum gave a colorless fraction. Preparative glpc gave 0.0969 g (28%) of 66 as a colorless oil (5', 3% SE-30, T -, = " — ' col 110 C) . The infrared spectrum (Neat, NaCl) displayed absorption bands at 3023 (w) , 2965, 2880, 1440, 1420, 1302, 1292, 1253, 1190, 1145, 1125, 1070, 1030, 1022 (sh), 1000, 965, 922, 906, 872, 840 cm"-'". The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 144 (11.1), 129 (9.2), 116 (15.7), 102 (24.8), 97 (35.7), 90 (100.0), 79 (23.4),

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134 54 (55.3) , 39 (31.0) , 19 (88.1) . Anal. Calcd for CqU-^^F^: C, 66.65; H, 6.99; F, 26.36. Found: C, 66.66; H, 6.91; F, 26.43 (diff ) . Re action of 2 , 4-dibromo-3 , 3-dif luorotricyclo [ 3 . 2 , 1 . 0^ ' 4 j q^^. 6-ene (63_) with Pheny l Azide (31^). In a 25 ml, 3-necked round bottom flask equipped with a nitrogen inlet and a magnetic stirrer were placed 1 , 2-dibromo-3 , 3-dif luorocyclopropene (1_5) (1.05 g, 4.48 mmol) , carbon tetrachloride (about 5 ml), and a few crystals of NaHC03. ^^^ mixture was stirred, cooled to 0° under nitrogen, and freshly distilled cyclopentadiene (about 2 ml, excess) was added. The resulting solution was stirred at room temperature for two days, after which no cyclopropene remained by gas chromatography (5', 20% SE-30, T^^-j^ 100 C) . The mixture was transferred to a 25 ml round bottom flask and the remaining cyclopentadiene was removed by aspirator vacuum. Then phenyl azide (1.5 g, excess) was added, and the resulting pale yellow solution was stirred at room temperature under nitrogen for three days, after which an nmr spectrum of the resulting brown-red slurry showed no vinyl proton resonances. The solution was filtered giving an off white solid, which when recrystallized from benzene gave white crystals of the adduct 67_ (0.3093 g, 16.5%, mp 166 167 C with decomposition). The infrared spectrum (KBr) displayed absorption bands at 3059 (w) , 2994 (w) , 1596 (s) , 1580 (sh), 1575 (sh), 1555 (sh), 1497, 1480, 1450, 1399, 1362, 1321 (w) , 1300 (sh), 1294 (w) , 1275, 1250

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135 (w) , 1230 (w) , 1209, 1173, 1119, 1103 (sh), 1081, 1068, 1033, 1010 (w) , 981, 959, 946, 924 (sh), 909 (sh), 886 (w) , 850 (w) , 795 (sh) , 783 (w) , 849 (s) , 690, 668 (sh) , 645 cm . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 393 (0.2), 392 (0.1), 391 (0.3), 390 (0.1), 389 (0.2), 313 (0.8), 312 (4.7), 311 (1.2), 310 (4.8), 256 (2.4), 254 (5.4), 252 (2.6), 231 (13.6), 230 (10.6), 211 (18.0), 194 (12.7), 192 (12.9), 117 (28.4), 105 (48.2), 77 (100.0), 51 (37.4) . Anal . Calcd for C3_4H-L2^N3Br2F2 : C, 40.12; H, 2.65; N, 10.03; Br, 38.14; F, 9.07. Found: C, 40.09; H, 2.66; N, 10.10; Br, 38.00; F, 915 (diff ) . Reaction of Norbornene with Phenyltrif luoromethylmercury and Potassium Iodide . In a 25 ml, 3-necked round bottom flask equipped with a magnetic stirrer and a reflux condenser were placed norbornene (1.41 g, 15.0 mmol) , benzene (approx. 10 ml), phenyltrif luoromethylmercury (1.03 g, 3.01 mmol, Ventron) , and dry sodium iodide (2.25 g, 15.0 mmol). The mixture was stirred and refluxed for 15 hours, at which time thinlayer chromatography (Eastman Si02/benzene or hexane) indicated no unconsumed phenyltrif luoromethylmercury . The pale yellow mixture was filtered, the filtrate was evaporated to volume of ca. 3 ml, and the residue was separated by preparative glpc (5', 3% SE-30, T^^^ 85°, 20 cc He/min) , yielding £6 as a colorless oil (0.119 g, 27.5%). The infrared spectrum

PAGE 144

136 (Neat, NaCl) displayed absorption bands at 3019, 2955, 3895 (sh) , 2864, 1480 (w) , 1455 (sh), 1444 (sh), 1436 (s) , 1414 (sh) , 1307 (sh), 1289, 1248 (s) , 1185 (w) , 1140 (sh) , 1120 (s), 1064, 1024, 998, 960, 921, 901 (s), 870, 846, 839 (d) cm . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 144 (13.3), 130 (11.4), 116 (42.4), 104 (25.6), 98 (38.5), 91 (100.0), 79 (69.4), 68 (21.9), 55 (53.7), 40 (39.5) , 19 (73.0) . Anal. Calcd for CgHj_QF2 : C, 66.65; H, 6.99; F, 26.36. Found: C, 66.84; H, 6.91; F, 26.25 (diff) . Thermal Behavior of exo-2 , 4-dibromo-3 , 3-dif luoro-8-oxatricyclo[3.2.1.0 ' ]oct-6-ene (2^). Three separate samples of l,2-dibromo-3 , 3-dif luorocyclopropene (15_) were dissolved in carbon tetrachloride (Spectrar) , and an excess of furan V7as added. Sample A was kept at room temperature, sample B was heated at 50° C, and sample C was heated at 75° C. After 5 days, the nmr spectra of the samples at room temperature and at 50 C showed no further change. However, the ''"^F nmr spectrum of the sample heated at 75° C showed signals for exo 20a as well as for endo ( 20 ) (see Table I) . The exo/ endo ratio was determined to be 2.69/1.00, based on """^F nmr integration. In a separate experiment, a 2:1 mixture of 20a: furan when heated at 80° overnight gave an exo / endo ratio of 3.3/1.0. This nmr sample after sitting at room temperature showed an exo / endo ratio of 2.64/1.0. Isolation of the endo isomer 2_0 proved to be impractical using column or thin layer

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137 chromatography. However, using gas chromatography (2,5', 3% SE-30, T^Qi 90 , 30 cc He/min), it was possible to isolate a fraction containing exo (2^) and endo (20a) in a ratio of 0.74/1.00. Significantly, this ratio remained approximately unchanged (0.68/1.00) when the nmr solution was allowed to stand at room temperature for one week. The 6 MHz """H nmr spectrum of this mixture showed no peaks other than the singlet at 6 6.8 (H . ) and the doublet at 6 5.2 (H^ ., , ) ^-^"-^-^ bridgehead' ' indicating the close resemblance of the ^H nmr spectra of the two isomers. Also, since the CDCl^ solution was rather 19 dilute, the F nmr spectra were run using F.T. to enhance resolution. The resulting values for chemical shifts and coupling constants are given in Table I for 2_0 and 20a, Thermal Behavior of exo-2 , 4-dibromo-3 , 3-dif luoro8-oxa[6,7]-benzotricyclo[3.2.1.0^''^]oct-6-ene (40) . An nmr sample of 40 was heated at 80° for eleven days, after which 19 time the F nmr spectrum remained unchanged when compared to the spectrum recorded before heating (see Table I) . H nmr Eu(F0D)3 ^^^^^^ Experiments of 3^ and 4_1. In an nmr tube was placed 3 , 3-dif luoro-8-oxatricyclo [ 3 . 2 . 1 . 0^ ' "^ ] octane (3^) (0.019 g, 0.13 mmol) in 500 ul of CDCI3 . Solutions of Eu(F0D)3 (200 mg , Eu(F0D)3 in 300 yl CDCI3) ^^^ ^^^^^ in 40 ul aliquots, and the ^H nmr spectrum was recorded after each addition. For each proton signal (H^, H2, H3, and H4) the change in chemical shifts (A6) was measured, and A6 in Hz was plotted vs. Avolume of Eu(F0D)3 solution in ul. The

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13i average slope over the linear portion of the graph was calculated for each type of proton {U-^, H^' ^3 , and H,). A similar experiment using 3 , 3-dif luoro-8-oxa[ 6 , 7 ] -benzotricyclo[3.2.1.0 ' ]oct-6-ene (4_1) v;as carried out (0.025 g, 0.13 mmol) in 500 yl of CDCI3. The comparative results for 3^ and 4^ are given in Table VI (p 49 ) . Attempted Preparation of 2 , 4-dibromo-3 , 3-dif luoro[ 6 , 7 ] [8,9]-dibenzotricyclo[ 3.2.1.0^^'^]nona-6,8-diene (_81) . In a sealed tube (Fischer-Porter) were placed anthracene (0.890 g, 5.00 mmol), 1 , 2-dibromo-3 , 3-dif luorocyclopropene (15) (1,75 g, 7.47 mmol), and approximately 25 ml of carbon tetrachloride (Spectrar) . The tube was capped and heated at 120° C for 4 days, after which nmr analysis of the crude reaction mixture showed approximately 50% of the anthracene remained. Another 1.0 g of cyclopropene was added, the tube was recapped, and the heating was resumed, this time at 130° C. After 3 more days, the nmr of the crude mixture showed no anthracene signals. The dark brown solution was concentrated and eluted through a silica gel column with benzene. Concentration of the first benzene fraction gave 1.94 g (94.2%) of a brown oily solid, which upon recrystallization from hexane gave 0.823 g of hard brown crystals (39.9%) which were 95% pure by nmr. A second recrystallization from hexane gave 0.314 g of analytically pure brown crystals, mp = 94° 97° C, which proved to be 2(bromodif luoromethyl) -3-bromo[ 5 , 6 ] [ 7 , 8 ] dibenzotricyclo[2.2.2]octa-2,5,7-triene (82). The infrared spectrum (KBr) displayed absorption bands at 3030, 3026, 3008,

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139 2889 (w) , 1616 (s), 1480 (w) , 1456 (s), 1321 (w) , 1308 (s), 1276 (s) , 1214, 1205, 1194, 1182, 1152, 1120 (s), 1099, 1068, 1017 (w) , 990 (s), 959 (s) , 936 (w) , 885 (w) , 864 (s), 855 (sh), 820 (s), 782, 758 (sh) , 742 (s) , 725 (sh) , 685, 660, 622 (s), 595, 555, 531, 482 (w) , 465 (w) , 449 (sh) cm . The mass spectrum (70 eV) shov/ed peaks at m/e (rel. intensity) 414 (3.1), 412 (6.7), 410 (3.5), 334 (49.5), 332 (50.5), 252 (82.6), 202 (100.0), 200 (74.5), 179 (65.5), 150 (78.9), 127 (30.3), 111 (44.8), 44 (23.4). Anal. Calcd for C^^U-^^Br^F^: C, 49.55; H, 2.45; Br, 38.79; F, 9.22. Found: C, 49.65; H, 2.51; Br, 38.96; F, 8.88 (diff) . Reduction of 2(bromodif luoro methyl) -3-bromo-[5, 6]-[7, 8]dibenzotricyclo [2.2.2] octa-2 , 5 , 7-triene (8 3 ) . In a 10 ml round bottom flask equipped with a magnetic stirrer were placed 2(bromodif luoromethyl) -3-bromo[ 5 , 6] [ 7 , 8 ] -dibenzotricyclo[2.2.2]octa-2,5,7-triene (8_2) (1.06 g, 2.56 mmol) , tri-nbutyltin hydride (2.24 g, 7.68 mmol), and a drop of di-tertbutyl peroxide. The flask was tightly stoppered, and the mixture was stirred and heated at 90° C for 15 hours. The resulting yellow solution was cooled, and careful chromatography on a neutral alumina column with hexane/benzene (1:1 v/v) gave a yellow solid. Recrystallization from hexane gave 0.245 g (37.3%) of crude product which when recrystallized from hexane/methanol gave 0.13 7 g white flakes, which was homogGneous to thin layer chromatography (silica gel/ chloroform; alumina/chloroform; alumina/benzene), mp 137.5° -

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140 o 138.0 C. This product proved to be 2(dif luoromethyl) [5,6][7.8]-dibenzotricyclo[2,2.2 ]octa-2,5,7-triene (8£) . The infrared spectrum (KBr) displayed absorption bands at 3064, 3019, 2964, 1640, 1452 (s), 1368 (s), 1320, 1288, 1244 (w) , 1198 (w) , 1190 (w) , 1164 (sh), 1149 (w) , 1107 (w) , 1059 (s), 1018 (sh), 994 (s) , 970 (sh), 930 (sh) , 899 (w) , 890 (w) , 842, 782, 750 (sh), 738 (s), 655, 620 (w) , 590 (w) , 537 (w) cm" , The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 254 (54.6), 233 (6.6), 203 (100.0), 202 (63.5), 178 (12.7), 152 (3.2), 151 (3.3), 102 (5.0), 101 (8.5), 87 (3.2), 76 (3.2). Anal . Calcd for C^^lij^^F^i C, 80.30; H, 4.76; Br, 0.00; F, 14.94. Found: C, 80.40; H, 4.75; Br, 0.00; F, 14.85 (diff ) . 75 Preparation of Bis(trimethylsilyl) -acetylene (85). In a 3-necked 11 Morton flask immersed in a dry ice/isopropyl alcohol bath, equipped with a high speed stirrer (Lab Line) and a 250 ml dropping funnel was placed Li (4.86 g, 0.17 gat) from freshly cut Li wire. The system was swept with nitrogen, then at -70 C, with stirring, was added trimethylsilyl chloride (32.6 g, 0.30 mol) in 200 ml dry tetrahydrof uran over a half hour. Then tetrachloroethylene (16.58 g, 0.10 mol) in 20 ml of tetrahydrof uran was added at -70° C over a half hour. The mixture was stirred rapidly (ca. 40% of stirrer capcaity) at -70° for 48 hours. The crude mixture was then allowed to warm to room temperature, and the contents of the flask were filtered. The resulting colorless, cloudy

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141 solution which, when distilled at atmospheric pressure under nitrogen, gave bis( triraethylsilyl) -acetylene (85) (12.00 g, 70.1%; bp 120° 137° C, lit. bp 134° 136° C. The nmr spectrum showed a sharp singlet at 6 0.16 ppm. Preparation of 1 , 2-bis(trimethylsilyl ) -3 , 3-dif luoro cyclopropene (86) . In a 50 ml round bottom flask were placed bis(trimethylsilyl)-acetylene (1.53 g, 9.00 mmol), benzene (15 ml), phenyltrifluoromethylmecury (1.03 g, 3.01 mmol), and Nal (1.35 g, 9.01 mmol). The mixture was stirred under nitrogen and heated to reflux for 7 days. The resulting dark mixture was cooled and filtered, and the solvent was removed under reduced pressure, giving a brown residue which by nmr analysis contained some product. The 1,2-bis(trimethylsilyl) 3, 3-difluorocyclopropene (8_6) was purified by preparative gas chromatography (5', 3% SE-30, T 75° C col 40 cc He/min, T^^ 100° C) as a colorless oil (0.1209 g, 18.3%), which polymerized at room temperature. The infrared spectrum (Neat, NaCl) displayed absorption bands at 2961, 2900, 1775 (w) , 1710 (w,br), 1662 (sh) , 1650 (sh) , 1649 (sh) , 1410 (w) , 1252 (s), 1182, 1019 (s), 872 (sh), 845 (s), 802 (w) , 755, 700 (w) , 680 (w) cm . The mass spectrum (70 eV) showed peaks at m/e (rel. intensity) 222 (0.2), 221 (0.8), 220 (1.2), 219 (2.7), 201 (1.6), 173 (0.6), 172 (1.6), 171 (3.7), 170 (17.6), 158 (2.7), 157 (15.7), 156 (36.2), 155 (100.0), 113 (33.7), 77 (52.4), 73 (64.6). Anal . Sample polymerized.

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REFERENCES 1. Huisgen, R., Grashey, R. , and Sauer, J,, in "The Chemistry of Alkenes" (S. Patai, ed.) pp. 878-929. Wiley (Interscience) , New York, N.Y., 1964. 2. Diels, 0., and Alder, K., Ann . Chem. , 460 , 98 (1928). 3. Seltzer, S., in "Advances in Alicyclic Chemistry" (H. Hart and G.J. Karabatsos, eds.) pp. 1-57. Academic Press, New York, N.Y,, 1968. 4. VJoodward, R.B., and Hoffmann, R. , "The Conservation of Orbital Symmetry", pp. 22-27, Verlag Chemie Gm bH, Academic Press, Inc., New York, N.Y., 1971. 5. Alder, K., and Stein, G. , Angew . Chem . , 50, 510 (1937). 6. Stockmann, H,, J. Org. Chem . , 26_, 2025 (1961). 7. Kwart, H., and Burchuk, I., J. Amer. Chem, Soc. , 74, 3094 (1952) . ~ — 8. Craig, D., Shipman, J.J., Kiehl, J., Widmer, F., Fowler, R. , and Hawthorne, A., J. Amer. Chem. Soc, 76, 4573 (1954). ~ — — — 9. Craig, D. , J. Amer . Chem . Soc. , 73 , 4889 (1951). 10. Berson, J. A., Reynolds, R.D., and Jones, W.M., J. Amer . Chem. Soc . , 78, 6049 (1956). ~ 11. Ganter, C, Scheidigger, U. , and Roberts, J.D., J. Amer. Chem. Soc., £7, 2771 (1965). 12. Berson, J. A., and Mueller, W.A., J. Amer. Chem Soc ^, 4940 (1961). ~ ' 13. Berson, J. A., Walia, J.S., Remaink, A., Suzuki, S., Reynolds-Warnhoff , P., and Willner, D. , J. Amer. Chem Soc. , 82, 3986 (1961). " — — ' 14. Berson, J. A., and Ben-Efriam, D.A., J. Amer. Chem. Soc, 81, 4083 (1959). 15 Wiberg, K.B., and Bartley, W.J., J. Amer. Chem. Soc, 82, 6375 (1960). ~ 142

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143 16. Sinunons, H.E., and Smith, R.D., J. Amer. Chem. Soc , 81, 4256 (1959). ~ 17. Muneyuki, R. , Yano, T., and Tanida, H., J. Araer. Chem . Soc . , 91, 2408 (1969). ~ ~^ 18, Martin, H.D., Chem . Ber . , 107, 477 (1974). 19. Monti, H., and Bertrand, M. , Tetrahedron, 29, 1565 (1973). — .20. Closs, G.L., Closs, L.E., and Boll, V7.A. , J. Amer, Chem . Soc. , 85, 3796 (1963). ~ 21. Battiste, M.A. , Tetrahedron Lett., 3795 (1964). 22. LaRochelle, R.W. , and Trost, B.M., Chem. Commun., 1353 (1970). 23. Srinivasan, R. , J. Amer . Chem . Soc. , 89, 4813 (1967). 24. Battiste, M.A. , and Sprouse, C.T., Tetrahedron Lett., 4661 (1970). 25. Longone, D.T., and Stehouwer, D.M., Tetrahedron Lett , 1017 (1970). 26. Tobey, S.W., and West, R. , Tetrahedron Lett., 1179 (1963). 27. Tobey, S.VJ., and West, R. , j. Amer. Chem. Soc, 88, 2478 (1966). ~ — 28. Tobey, S.W., and West, R. , J. Amer. Chem. Soc, rr 2481 (1966). ~ ---' 29. Breslow, R. , Ryan, G., and Groves, J.T., J. Amer. Chem Soc , 92, 988 (1970). " " 30. Sargeant, P.B., and Krespan, C.G., J. Amer. Chem. Soc, 91, 415 (1969). 31. Sargeant, P.B., J. Amer . Chem . Soc . , 91, 3061 (1969). 32. Mahler, W. , J. Amer. Chem . Soc . , 84, 4600 (1962). 33. Cullen, R. , and Waldman, M.C., Can. J. Chem., 47, 3093 (1969) . — 34. Crabbe, P., Carpio, H., and Fried, J.H., J. Org. Chem., 28, 1478 (1973). 35. Law, D.C., and Tobey, S.W., J. T^jner. Chem. Soc, 90 2376 (1968). ~ —

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144 36. Magid, R.M., and Wilson, S.E., J. Org. Chera. , 30, 1775 (1971). " — — 37. Battiste, M.A., Kapicak, L.A., Mathew, M. , and Palenik, G.J., Chem . Commun . , 1536 (1971). 38. Bordner, J., and Howard, G.R., Crys t. Struct. Comn. , 4, 131 (1975). 39. Halton, B. , and Milson, P.J., Chem . Commun., 814 (1971). 40. Herndon, W.C, and Hall, L.H., Tetrahedron Lett., 3095 (1967). 41. Bovey, F.S., "Nuclear Magnetic Resonance Spectroscopy", (Academic Press), New York, N.Y., 1969, pp. 209-228. 42. Kienzle, F. , Helv. Chim. Acta . , 58, 1180 (1975). 43. Jefford, C.W., and Wojnarowski, W. , Tetrahedron, 25, 2089 (1969). — 44. Jefford, C.W., and Hill, D.T., Tetrahedron Lett., 1957 (1969). 45. Sprouse, C.T., Ph.D. Dissertation, University of Florida, 1969. 46. Nielson, W.C, Ph.D. Dissertation, University of Florida, 1974. 19 47. Mooney, E.F., " F nmr Spectroscopy", Varian Assoc. 48. Prinzbach, H., and Martin, H.D., Hel v. Chim. Acta., ^, 438 (1968). " 49. Jefford, C.W., Gehret, J.C.E., Mareda, J., Kabengele, N.T., Graham, W.D., and Burger, U., Tetrahedron Lett., 823 (1975). 50. Deem, M.L., Synthesis , 675 (1972). 51. Huisgen, R. , Grashey, R. , and Sauer, J., in "The Chemistry of Alkenes" (S. Patai, ed. ) p. 837, Wiley (Interscience) , New York, N.Y. , 1964. 52. Warrener, R.N., J. Amer. Chem . Soc . , 93, 2346 (1971). 53. Filippo, J.S., Jr., Nuzzo, R.C., and Romano, L.J., J. Amer . Chem. Soc., 97_, 2469 (1975). 54. Vogel, E., Korte, S., Grinime, W. , and Gunther, H., Angew. Chem. Internat . Ed. , 1_, 289 (1968).

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14; 55 70, deWit, J., and Wynberq, J., Rec. Trav . Chin , de PaysBas, 92, 281 (1973). 56. Cross, A.D., and Landis, P.W., J. Amer. Chera. Soc, 8^, 1736 (1962). ^ 57. Cross, A.D., and Landis, P.W., J. Amer . Chem. Soc, 8^, 4005 (1964). " 58. Cross, A.D., J. Amer . Chem . Soc . , 86 , 4011 (1964). 59. Akhtar, M. , Chadwick, J.C., Francis, S.A., and Fray, G.I., Tetrahedron , _31, 601 (1975). 60. Jefford, C.W., Hill, D.T., Ghosez, L. , Toppet, S., and Ramey, K.C., J. Amer. Chem . Soc . , 91, 1532 (1962). 61. Seyferth, D. , Hopper, S.P., and Darragh, K.V., J. Amer . Chem. Soc . , 91, 6536 (1969). 62. Simmons, H.E., Blanchard, E.P., and Smith, R.D., J. Amer . Chem . Soc . , 86 , 1347 (1964). 63. Sauers, R.R., and Sonnet, P.E., Tetrahed ron, 20, 1029 (1964). 64. Ghosez, L., Slinckx, G. , Glineur, M. , Hoet, P., and LaRoche, P., Tetrahedron Lett ., 2773 (1967). 65. deMeijere, A., and Weitemeyer, C, Angew. Chem. Internat. Ed., 9_, 376 (1979). 66. Haywood-Farmer, J., Pincock, R.E., and Wells, J.I., Tetrahedron , 22 , 2007 (1966). 67. Battiste, M.A., and Brennan, M.E., Tetr ahedron Lett., 5857 (1966) . 68. Klumpp, G.W., Verfking, A.H., deGraaf, W.L., and Bickelhaupt, F., Justus Liebigs Ann . Chem., 706, 47 (1967). 69. Halton, B., Battiste, M.A., Rehberg, R. , Deyrup, C.L., and Brennan, M.E., J. Amer. Chem. Soc, 89,^5964 (1967) Jefford, C.W., Kabengele, N.T., Kovacs, J., and Burger, U., Tetrahedron Lett., 257 (1974). 71. Jefford, C.VJ. , Gehret, J.C.E., Mareda, J., Kabengele, N.T., Graham, W.D., and Burger, U. , Tetrahedron Lett., 823 (1975). 72. Lindsay, R.O., and Allen, C.F.H., Org. Svn., Ill, 710 (1955) . ""—

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146 73. van der Kerk, G.J.M., Noltes, J.G., and Luijten, J.G.A., J. Appl. Chem. , 7, 366 (1957). 74. Alder, K. Ache, H.J., and Flock, F.H., Chem. Ber., 92, 1888 (1960) . ~ 75. West, R. , and Quass, L.C., J. Organometall . Chem., 18, 55 (1969).

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BIOGRAPHICAL SKETCH Robert Giles Posey was born on September 18, 1947, in Plainfield, New Jersey, to Ralph T. and Amanda H. Posey. His early childhood was spent in Cranford, New Jersey, and a subsequent move to Washington, New Jersey, resulted in his completion of high school in 1965 at Washington High School. He received the degree of Bachelor of Science with a major in Chemistry from Furman University in Greenville, South Carolina in 1969, and after an additional year at Furman he completed the requirements for the degree of Master of Science, which was awarded in 1971. While at Furman, he married the former Phyllis Ann Hollingsworth of Travelers Rest, South Carolina, in 1969 and became the father of a son, Will, born on September 22, 1974. Upon completion of his studies at Furman, Mr. Posey entered the Graduate School at the University of Florida in the Fall of 1970 as a Graduate Teaching Assistant for continued study in organic chemistry. Mr. Posey is a member of the American Chemical Society. 147

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I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. //'•" ('/ ^im M. A. Battiste, Chairman Professor of Chemistry I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy, (>,//'.2W. M. Jones "'' Professor of Chemistry I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy, iAU^. (:' M^Li:-tL']J =h W. R. Dolbier, Jr. Professor of Chemistry I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. Gus J. Palenik Professor of Chemistry

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I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Doctor of Philosophy. E. (fl Sander Associate Professor of Biochemistry This dissertation was submitted to the Graduate Faculty of the Department of Chemistry in the College of Arts and Sciences and to the Graduate Council, and was accepted as partial fulfillment of the requirements for the degree of Doctor of Philosophy. December, 1975 Dean, Graduate School

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UNIVERSITY OF FLORIDA 3 1262 08553 0581


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