Title: Structural studies of 4 + 2 perhalocyclopropene cycloadducts
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Permanent Link: http://ufdc.ufl.edu/UF00098677/00001
 Material Information
Title: Structural studies of 4 + 2 perhalocyclopropene cycloadducts
Physical Description: viii, 147 leaves : ill. ; 28cm.
Language: English
Creator: Posey, Robert Giles, 1947-
Copyright Date: 1975
Subject: Cyclopropenes   ( lcsh )
Chemistry thesis Ph. D
Dissertations, Academic -- Chemistry -- UF
Genre: bibliography   ( marcgt )
non-fiction   ( marcgt )
Statement of Responsibility: by Robert Giles Posey.
Thesis: Thesis--University of Florida.
Bibliography: Bibliography: leaves 142-146.
General Note: Typescript.
General Note: Vita.
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Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved by the source institution and holding location.
Resource Identifier: alephbibnum - 000161491
oclc - 02676452
notis - AAS7832


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To Phyllis and Will


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.



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


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


1H and 19F

1H and 19F

1H and 19F

1H and 19F

1H and 19F

34 and 41..



11 nmr and


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

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










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



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['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-
[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-

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['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.




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


<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




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['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['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-

[,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['4]oct-6-

ene, as shown below.

CH3 +


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['4]-
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-

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]


T 7.72 2 T 7.27 H C

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['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

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
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
1.62 (d of d) Jbx= 6.74


H 2.94
Hb 1.80

(mult) J(Hz)

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


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


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-

[',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

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


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
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
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


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

H (6.83)


C1 Ib
SF H C1 ib(5.26)

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


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
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-
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


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

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 =

F F=
b c


H F =3.2
a,b a

Table I Continued

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


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
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

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-
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
3 No such coupling is reported for 21 and no W /2

data were cited for the F doublet. The anomalies

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
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

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-


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

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


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
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 +
S CH3Li -

66.45 H

26% 74%

carbene additions to bicyclic systems such as norbornadiene

proceed to give preferentially exo addition products has
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['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['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







mult. splitting, Hz assign.






128.1 7

134.8 M

221.0 M










2 X 2


2 X 7


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


2.8, 2.6

H He
, _, e


H H =10.5
e f
H F =6.3

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

F H =4.3
a a,b

F H -2.3
c a,b
FE 14

fC, e

HeH= 8.6

F CF 3=19.0
a 3

F CF =2.6


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
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

61.7 2 X 2 19.0, 2.6 CF3

109.4 7 X 2 19.0, 8.5 F
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

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

H H1
Cl 3

H H411

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
by Sargeant, though, F appears as a clean septet coupled
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



F 3.57

YF3 2.01

CF3 1.15














mult. splitting, Hz

2 X 2


2 X 7

2 X 3




W1/2 ~ 5.5

W1/2 6.5

W1/2~ 4

W1/2 8

19.0, 2.6


2.8, 2.6


1/2 ~ 6.5

W1/2~ 5

W1/2 7

19.0, 2.6

19.0, 8.5


assign. J,Hz

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

f FaFb=178
e FbH?=2.8



H II=8.4
F CF =19.0
a 3


FaH =8.5

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.


CF3 CF3 /CF3

3 F2
17 27a 28a 2

(31%) (69%)



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
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.

F (n-Bu) 3SnH F

S F \ F

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


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.



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['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"

4 Br
F 80C / Br

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

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

11r Br

Br 12
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

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.

20 + N3 ->


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





o C



u Q


C )

U 0

ciI-i) 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
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

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
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
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
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
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
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
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
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


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


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

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-
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-


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
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


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
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
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

individual 1F resonances must be assigned to the proper
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
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


15 + a BrF
H Br

discussed previously. Once again, reduction of 40 to 41

with tri-n-butyltin hydride allowed confirmation of the
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
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.
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












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


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
will weakly coordinate to 9F (and produce contact shifts

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

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


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





42 F2


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



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

_ _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 _

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-
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
represented 45 as 45b only, based on the 1F couplings to

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
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

Br Br

/Br / H Br
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)

3 Br


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

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-
tic triplet for F in the F nmr with cis-vic coupling
JF H of 14.0 Hz. Unfortunately, the remainder of the 19F

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

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

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

48 appeared as a doublet (J = 161.0 Hz) of doublets
(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
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['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


"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
53b, R = CH3

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

lower. This fact combined with the much greater ground
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


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
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
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
in 53a and 53b. This indicates the similarity in the

Table VII
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

6Fb 131.96 132.65 142.77


Br Br H
Br r
51b 52b 53b

6F 110.56 124.14
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
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

Fb a Fb a

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

of exhibiting the differences shown in Table III. Therefore,
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[ 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
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[ ]octan-

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

fluorine substituents on reactivity in the tricyclo[]-

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

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


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


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
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

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
data for it were accumulated, including the 19F nmr chemical

shifts. The technique used previously to firmly establish
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
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,
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


Fa F F
b b a Fb a

"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

a FaF /a


"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
the F atom is a or 8, as shown below. In 59, the -CH3

1 1


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


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
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.





A third indication of exo stereochemistry in 58a

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
Comparison of 19F Nmr Chemical Shift Data

F 124.10 F 127.82

F 81.94 F 81.07
a a

57a Br

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
(t-BuO) /2

64 1 66 1

N3 F


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
analysis. As expected, in the F nmr spectrum F appeared
at lowest field as a doublet (W-/2 = 3.6 Hz; JF F = 145.5
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
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


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
and the high field half at 61.32 to H is based on the
expected shielding of H by the cyclopropane ring. The
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
H JFH = 3.5 Hz
2 1


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
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 -- <---


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

68 70 69

Similarly, bromofluorocarbene (:CFBr) gave the analagous

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

Br -->

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.
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


801c +

74 ~2 75

products were isolated, as shown below. The absence of

any endo-tricyclo[ ]octyl compounds is not surprising


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['4 oct-6-ene.

20HC -H

2 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[ 4]oct-6-enes, as shown

below. Accurate structural assignments in these tricyclic

H3 .H3 CH- F


77 78


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.




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
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.

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

(69%) (31%)

C3F2 2000C
C F3


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
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


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




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
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[,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 F

15 81

(n-Bu)3SnH H 2


82 ------> +0


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]?-

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
2 .
(CH3)3Si-C-C-Si(CH3) ---> F2


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.






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