SYNTHESES AND REACTIONS OF 1-SUBSTITUTED

TRICYC LO 13.2,.1.03' 61 OCTANES

Lei Keng Lon( 李景倫）

A thesis submitted in partial fulfilment of the

requirements for the degree of

Master of Philosophy in

The Chinese University of Hong Kong

1980

Thesis Committee:

Dr. T. Y. Luh, Chairman

Dr. T. L. Chan

Dr. C. N. Lam

Prof. C. Eaborn, External Examiner

CONTENTS

Acknowledgements

Abstract

Introduction

Synthetic Plan

Results and Discussion

Experimental

References

1

2

9

12

45

64

ACKNOWLEDGEMENTS

The author wishes to express his gratitude to Dr. T.Y. Luh

for his invaluable advice, guidance and unfailing encouragement

in the research work and the preparation of this thesis.

He is also indebted to Mr. Y.H. Law and C.P. Yuen for

meesaring mass spectra and 13C-nmr spectra, respectively.

Department of Chemistry, Lei Keng Lon

C. U. H. K.,

June, 1980.

1

ABSTRACT

1-Carboethoxytricyclo[3.2.1.0396]octane was synthesized

from 5-allyl-5-carboethoxy-2-cyclopentenone in-two steps

in excellent yield. Seven other 1-substituted tricyclic

compounds were prepared. The pKa of the corresponding

carboxylic acid was determined in methanol-water (50/50,

v/v) and ethanol-water (50/50, w/w). The selectivity of this

bridgehead radical in the halogen abstraction reaction was

examined. The enhanced acidity of the carboxylic acid and

radical selectivity by comparing with those of related

systems are attributed to the increase of strain in this

system. In addition, solvent assistance was found important

in the acetolysis of 1 tr icyclo[3.2.1.03'6 3octylmethyl

tosylate on the basis of activation parameters and product

distribution.

2

INTRODUCTION

The chemistry of strained ring compounds has been one

of the most popular research area in organic chemistry.1,2

In addition to the challenging synthetic problems involved,

many of these systems have exhibited interesting physical

and chemical properties as well. Tricyclo[3.2.1.0 3,6]octane

(1) (as referred to tricyclooctane below) is an interesting

molecule to be studied because its strain energy is about

25 Kcal/mol higher than that of norborane due to the presence

of the cyclobutane moiety in the former case. This molecule

can also be considered as one of the isomers of bisnor-

adamantane with two carbon atoms less than adamantane.

7

76

12 18

5

8365 3

24 4

(1)

It was not until 19b6 that Sauers and his coworkers3

achieved the first successful synthesis of this hydrocarbon

where the cyclobutyl ring was constructed by a novel ring

closure reaction. Their synthetic route is summarized in

Scheme I.

SCHEME I

Wolff-Kishner

reduction

Na/toluene

ii

Subsequently, a number of tricyclooctane derivatives

have been synthesized. For example, in a closely related

sequence, the ester (3) underwent cyclization on treatment

with potassium t-butoxide to afford 4~substituted

derivatives of tricyclooctane.

4Hunsdiecker

reactio

ICO2 N

Br

Later, Monti and his associates reported the synthesis

of tricyclo[3.2.1.0 3'6Joctan-7-one (4 5 and 6-chloro-

tricyclo[3.2.1.0 3'6]octan-7-one (5)6'7 where the key step

leading to the requisite cyclobutane moiety remains the

intramolecular nucleophilic substitution. Compound (5) is

the first known compound with substituent at bridgehead

position of this tricyclic system. The important reactions

leading to the syntheses of (4) and (5) are listed in

Scheme II and III, respectively.

The chemistry of this tricyclooctane has not been fully

explored. However, the study of reactions involving cationic

intermediates at C-2 has revealed a remarkable resistance to

rearrangement.3 Accordingly, the tosylate (6) and (7) were

synthesized and solvolyzed in buffered acetic acid-3

Surprisingly, exo-acetate (8) was the sole product from

either reaction; and (6) solvolyzed with substantial(10 2'8)

anchimeric assistance in the ionization step.3 Sauers

suggested that it could conveniently be rationalized by

SCHEME II

postulation of nonclassical or rapidly equilibration ions

3formation.

6SCHEME III

0 OBr

Zn/Cu1) .Fe2(CO)9

2) .Br2CH000HBr2

Br

0

cl HCr02Cl1) .Na/EtOH 0MsOMs

2).MsC1,

Et3N

0

C

ButOK

C6H6

(5)

On the other hand, the solvolysis of the tosylate (9)

afforded a rearranged product (10.8 This implies that

rearrangement will readily occur when a carbenium ion is

generated at the C-4 position.

NoAcOTS

OTSH

H

(7)(8)(6)

Interestingly, 2-substitoted tricyclooctanes (11) were

readily obtained from the solvolysis of 2-chlorobisnor-

. 9adamantane 12). Strain energy release was proposed for

this reaction.

The bridgehead reactivities of various compounds have

1 0been studied in detail. However, the syntheses of the

tricyclooctane derivatives with substituent at the bridge¬

head 1-positiori have not been reported. In this work, we

investigated the physical organic chemistry of this tricyclo¬

octane from the viewpoint of free radical chemistry and

carbocation chemistry. In the area of free radical chemistry

we examined the selectivity of the 1-tricyclooctyl radical

in the halogen abstraction reactions. We also studied the

acidity of the carboxylic acid (13) to examine the influence

of the skeletal rigidity on acidity in this tricyclic

system.

In the area of carbocation chemistry, we investigated

the tricyclooctylcarbinyl system (14) to assess the impact

of high strain energies on Wagner-Meerwein rearrangements

and the solvent assistance in the solvolysis of neopentyl

system.

Because both (13) and (14) can be prepared from the

same precursors 1-carboethoxytricyclo [3.2.1.0 5,j octane

(15) by hydrolysis and reduction, respectively, the first

aim in our work is to the synthesis of this highly interest¬

ing compound (15)•

9

SYNTHETIC PLAN

All known procedures3-7 for the preparation of tricyclo-

octane nucleus could not readily be applicable to the

synthesis of (15) because suitable precursors could not

easily be obtained. Consequently, a new, convenient scheme

has to be developed.

The construction of the cyclobutyl ring in (15) can be

viewed as a result from an intramolecular, light induced,

[2+2] symmetry allowed cycloaddition11 of 4-allyl-4-carboethoxy-

nvn1nnentene (16)

CO2C2Hsco caH

[2+2J-COZCXHs

hp

(15)16)

To the best of our knowledge, only two examples have

been reported. The photolyses of prostaglahdine derivative

(17) 12 and 4-methyl-5-allylcyclopentane-1,3-dione-3-enol

acetate (20)13 afforded the tricyclooctane derivatives (18)

and (19) and (21) and (22), respectively. These results

stimulate us to investigate if (15)can also be prepared

10

in the same manner.

0OH

0

OH CsH11CsH11

CO2Me

0hv/THF Cs H11

-78oC

HOH CO2Me Mao2c

H(18)(17)

(19)

o

oby/hexane OAc OAc

Ac0

(22)(21)(20)

The synthesis of (16) is not so straightforward.

However, the cyclopenterione derivative (23) would be much

easier to prepare. Indeed, all known instances described

O

Co2C2H5

(23)

11earlier 12,13 involve the cyclopentenone moiety in cyclo-

addition reaction. Nevertheless, two photoadducts (24) and

(25) would be expected in view of different orientation of

the "exciplex,"14 (26) and (27). This drawback should not

be a difficult problem because either (24) or (25) could

be selectively reduced to (15) with ease.

Co2C2H5CO2C2H5

00[2+2]

(24)(26)

0 0

cozc1H5co2c2H5

[2+2]

(25)(27)

12

RESULTS AND DISCUSSION

I.SYNTHESIS

Our first synthetic target was to prepare the cyclopent-

enone synthon (23). 2-Carboethoxycyclopentanone (28) readily

available from the Dieckmann condensation 15 of diethyl

adipate 16 was chosen as the starting material. 2-Carboethoxy-

cyclopentanone (28) was converted to 2-allyl-2-carboethoxy-

cyclopentanone (29) in 90% yield by treatment with base

followed by allyl bromide.17

00

r.t.

1).ButOK/DMP

C02C2H5

2). allyl bromide,

(29)(28)

A number of method is known to transform saturated

ketone derivatives to the corresponding enones.18,19 One

of the important procedures is d-bromination followed by

dehydrobromination reactions.18 However, the reaction

conditions are generally vigorous and the yield varies.

13These methods could not be applied to our system because

the double bond could be brorninated. Indeed, (29) was treated

with two moles of bromine to give the tribromoproduct (30.20

Br

0

BBr

BrCHC13C02C2

2Br2

02CZrir.t.

(29) (30

Various oxidizing agents such as oxygen in the presence

of transition metal catalysts,19a dichlorodicyanoquinone,19b

pyridine N-oxide-acetic anhydride,19c selenium dioxide,19d,19e

periodic acid19f were found to transform saturated carbonyl

compounds to the corresponding enones but yields vary greatly,

and the effective control of regioselectivity is frequently

a problem.

The ultility and versatility of organoselenium compounds

has become apparent.21 Recently, Reich and his coworkers22

reported that oc, -unsa.turated carbonyl compounds (32) could

be conveniently obtained from the oxidation of a(-arylseleno

carbonyl compounds (31).

The organoselenium compounds (31) can easily be synthesized

by treatment of the enolate of (33) with the arylselenenyl

halide (ArSeX).

Consequently, these methods may provide an alternative

procedure to prepare the desired synthon (23) from (29)• On

treatment with lithium diisopropyl amide (LLA) in the

P T

presence of hexamethylphosphoric triamide (hmpt), 5 (29) was

first converted to enolate (34) which reacted with benzene-

selenenyl bromide to give 5-phenylseleno-2-allyl-2-carboethoxy-

cyclopentanone (35).

Oxidation of the selenide (35) with hydrogen peroxide

afforded a mixtrue of 5-allyl-5~carboethoxy-2-cyclopentenone

(23) and 2-allyl-2-carboethoxycyclopentanone (29) in a ratio

one to one.

The recovered saturated ketone (29) could only be formed

from the selenoxide fragmentation. Detailed mechanism is

unknown. However, approximately equal amount of isomeric

trans selenide (36) and cis isomer (37) would be formed

from the selenation reaction because the steric environment

for carboethoxy group and allyl moiety would be about the

same.

If the carboethoxy and the phenylseleno groups are

cis, intramolecular reaction may occur during the course

of oxidation. A plausible mechanism is outlined in Scheme

IV. On the other hand, the trans isomer would not be

possible to proceed via this cyclic transition state (or

intermediate), (38); and therefore, normal syn elimination

would occur in this case. Although no solid evidence supports

this mechanism, the scheme may provide a reasonable

explanation on this observation.

SCHEME IV.

(37) (38)

(29)

(36)

(23)

The structure for the enone (23) was unambiguously

proved on the basis of the pmr spectrum which exhibits two

multiplets at% 6.10 andS 771 ppm correlated to the

olefinic protons in the cyclopentenone moiety. The mass

spectrum which exhibits a molecular ion peak at me 194

and base peak at me 121 is consistent with

the structure.

12Irradiation (400W, medium pressure) of 5-allyl-

5-carboethoxy-2-cyclopentenone (23) led the concurrent

formation of 1-carboethoxytricyclo[3.2.1.0 '3octan-2-one

(24) and 1-carboethoxytricyclo[3•2.1.0 '°}octan-7-one (25)»

(71o, ca. 1 0:1). The isomers were respectively formed from

the dienes (26) and (27) which differ in orientation only.

Attempts to seperate the isomers were not successful.

1 3The isomer ratio was determined by integrating C-nmr

spectra of the mixture with the aid of proton decoupling

without nuclear overhauser effect technique. Compound (24)

would be expected to exhibit eleven different signals for

eleven carbons. On the other hand, compound (25) would

show only nine absorptions because the skeleton possesses

1 3a C symmetry. The C-nmr spectrum for this mixture showed

s

eleven major peaks of equal intensity in addition to six

miner peaks. The eleven major signals which appeared at

£14.2 (CH), 54.6 (C-5), 56.0 (c-4), 58.8 and 40.4 (C-7 and

C-8), 40.9 (C—6), 45.2 (C-5), 60.9 (CH2-0), 65.8 (C-1),

169.9 (C02-), 210.9 (C-2) ppm were assigned to the absorptions

of the unsymmetrical product (24) Six minor signals at

i

£50.1 (C-5 and C-5), 56.0 (C-2 and C-8), 56.4 (C-4), 42.4

(C-6), 61.2 (CH2«0)_ ppm were'believed to be the absorptions

for the minor product (25)• It is noteworthy that the peaks

for C-1, the two carbonyls and methyl carbon were missing

and may be embodied in the absorptions for (24).

In general, the orientation of the £2+2] cycloaddition

of enones to olefins is influenced by electronic and steric

2 Aeffects. If the steric environment is similar, the

orientation of the cycloaddition reaction will depend on

the electron density distribution in the substrates. For

example, compounds (39) and (40) in addition to a small

amount of side products were isolated from the photolysis

of a mixture of isobutene and cyclohexenone in 33% and 6%

.., 25respectively.

Thus, compound (39) is referred to an electronically

correct product where the -carbon of the cyclohexenone

is bonded to the more substituted carbon atom of the olefin.

Moreover, irradiation of the oxa-enone (41) in isobutene

14afforded the electronically correct product (42) only.

Furthermore, similar results were obtained in the

intramolecular [2+2] photocycloaddition reactions. For

example, upon irradiation the electronically correct

product (43) was obtained quantitatively from the substituted

14cyclohexenone (44).14

(44) (45)

The photolysis of the enol acetate (45a) led the

photoproducts (46a) and (47a) with a ratio of seven to

three. However, irradiation of (45b) afforded approximately

1 5equal amount of two isomers (46b) and (47b).

(45) (46)

The latter observation is understandable because the

electronic effect caused by the alkyl substituents at both

ends of the olefinic double bond in the side chain would

be the same. On the other hand, compound (46a) is still an

electronically correct product and was in fact obtained

as the major product. This argument can be supported by

the result of the photolysis of the prostaglandin derivative

(17) where two isomeric products (18) and (19) (44:56)

1 2were obtained. These results, compared with ours, agree

well to the general model of the photocycloaddition reactions.

Without seperation of the isomers, the mixture (24)

and (25) was treated with methyl mercaptan in ether catalyzed

0 26-28by borontrifluoride etherate at 0 C to afford the

corresponding thiolketals (48) and (49)•

Without further purification, the mixture (48) and (49)

29was refluxed with W-2 Raney nickel in ethanol- to yield

1-carboethoxytricyclo[3•2.1.0' J octane (15) in 90$.

The structure of (ip) was unambiguously proved.

1 3particularly, by C-nmr spectrum which exhibits only

nine signals at 614.2 (CH), 34-6 (C-3 and C-5) 35-9

(C-4), 41.0 (C-2 and C-8), 43-2 (C-6), 44.0 (C-7),

53-1 (C-1), 59.9 (CHO), 175-3 (CO) ppm. These spectral

data firmly establish that (15) is a symmetrical molecule.

On treatment with excess lithium aluminium hydride in

50tetrahydrofuran, the ester (15) was converted to

1-hydroxymethyltricyclo[3.2.1.0 Joctane (50) in 89%.

1 3The structure was proved mainly by its C-nmr spectrum

_ -and infrared absorption at r=3368 cm with no band in

the carbonyl region.

The alcohol (50) was reacted with p~toluenesulfonyl

chloride and pyridine to afford the corresponding tosylate

(64) in 4% yield. This compound was used to study the

solvolytic reaction which will be discussed later.

(50) (64)

On treatment with refluxing aqueous sodium hydroxide

solution (20%), the ester(15) was smoothly hydrolyzed to

give the corresponding carboxylic acid (1 5) in 91%.

(15) (15)

Tricyclop.2.1.0' J octane-1-amine hydrochloride (52)

was obtained from tricyclo[3•2.1.0' 3 octane-1-carboxylic

31acid (13) in 71% by Curtius rearrangement.

Attempts to neutralize the amine hydrochloride solution

with base in order to isolate the free amine were not

successful. Instead, decomposed products with unknown

structure were observed. Indeed, various bridgehead amines

The mixture exhibited the following spectral data: ir (neat)

V=3548 cm-1; pmr (CDCl,) S 1• 18-2.05 (7H,m), 2.18-2.72

2.94 (.2H, s), 3.61 (4H,m) ppm, 13C-nmr (CDC1) g 29• 1 (t),

29-9 (.t), 35-0 (d), 35.2 (t), 41.9 (d), 44-9 (t), 45.0 (.t),

46.5 (t), 61.4 (t), 61.7 (s) ppm 9 highest me: 123.

such as 1-tricycloTj.1.1.0 Jheptyl (55) and cubyl amines

(56) were found unstable and underwent homoketonization

leading to decomposition.

By using the Cristol-Firth modified Hunsdiecker

reaction the bridgehead bromide (57) was obtained

in dibromomethane from tricyclo[3.2.1.0 'Joctane-

1-carboxylic acid (13) in 70%.

The reaction is known to proceed via a free radical

32mechanism; hence the smooth transformation as observed

in the tricyclic system may reflect the relative stability

of this highly strained bridgehead radical and will be

discussed later.

Again, the bridgehead chloride (58) could be prepared

32by analogous reaction in carbon tetrachloride. Actually,

a mixture of bromide (57) and chloride (58) was obtained

and seperated by preparative gas chromatography.

It is interesting to note that all compounds with

tricyclo .2.1.0 'h°ctane skeleton exhibited a strong

peak (usually base peak), which may be arised

from three-bond cleavage to lose a fragment.

13The C chemical shifts for 1-substituted tricyclooctane

derivatives are listed in Table I. Assignments were made on

the basis of relative signal intensities and verified by

their off-resonance decoupled spectra and also with the

aid of proton decoupling mode without nuclear overhauser

effect. The most intense peaks were assigned to the doubly

degenerate carbons C-2,8 and C-35? and their assignments.

were confirmed by the observed multiplicities in their

off-resonance decoupled spectra. The remaining four signals

in order of decreasing intensity (presumably due toI,

increased relaxation time) were assigned to C-7 ojo C-4»

C-6 and C-1 which bear two, one and no hydrogen substituents,

respectively. The signals of C-4 and C-7 carbon atoms

(both carry two hydrogen atoms) were differentiated on

the basis of relative substituent shifts compared to the

related bicyc.lo [2. 2. 1 heptane derivatives, whose signals

34have been unequivocally assigned.

It is noted that when an electron-withdrawing substituent

is attached to the bridgehead 1-position of the tricyclooctanes,

the chemical shift of the o(-carbon atom will be more downfield

than that of the other ring carbon atoms. This would be

plausible arised from an inductive effect being transmitted

through the bonding network.

Table I

1 5

C Chemical Shifts (ppm) of 1-Substituted

Tricyclofj•2.1.0 1 octanes in CDC1,5

X

48.8

50.9

52.9

53.1

60.1

60.0

40.5

40.0

40.9

41.0

40.8

40.0

34-9

34.8

34.7

34.6

35-3

33.6

35.9

35.9

35.8

35.9

36.1

34.4

43-1

43.0

43-6

43-2

48.3

40.3

42.6

41-9

44.2

44.0

49.4

41.8

65-4

66.3

182.5

59.9 175.3 14.2

Another significant feature is that the chemical shifts

of all the ring carbon atoms in the tricyclooctane

derivatives appeared at lower field than those of related

54

bicyclo [2.2.1] heptane derivatives (59). This is apparently

attributable to the increase of strain in the tricyclooctane

molecules.

II. pKa MEASUREMENT:

Benzoic acid was employed to check the method. The

pKa obtained agreed well to the literature values.55,36

5 61The pKa of tricyclo [3.2.1.0' Joctane-1-carboxylic acid

(13) was determined in 0% (v) methanol-water and 5Ofo (w)

I

ethanol-water to be 5.89 and 6.52, respectively. Comparing

our results with the previous works on related compounds

in Table II, the tricyclooctane carboxylic acid (13) is

a stronger acid than the bicycloheptane carboxylic acid

(60) and bicyclooctane carboxylic acid (61). This is

consistent with increasing the total strain of the

tricyclooctyl molecule by introducing the cyclobutane

moiety, and thus the s_ character in the tricyclooctane

37C-1 exocyclic orbital is enhanced.

32Table II

The pKa values of Bridgehead Carboxylic Acids

Determined in Various Solvent Systems At 25 C

50% (v) methanol-water 1 50% (w) ethanol-waterCarboxylic Acids

co2H

6.04(a)

cozN

6.87(b)6.26(a)

CO2H

( c)6.525.89(c)

(a) Ref. 38.

(b) Ref. 39, 40.

(c) This study.

Ill, SELECTIVITY STUDY OF HUhSDIECKER REACTION.

By using the Cristol-Firth modified Hunsdiecker

32 33reaction,the procedure of Ruchardt and his coworkers%'

was employed. Thus, tricyclo [3.2.1.0 octane-1-

carhoxylic acid (13) (1 equiv.) was treated with mercuric

oxide (red, 1 equiv.) and bromine (1 equiv.) in carbon

O

tetrachloride (100 equiv.) at 80 C for 1h, a mixture of

the bromide (57) and the chloride (58) was obtained in a

ratio of 41 to 59- results are compared with related

studies as summarized in Table III.

The most striking feature of the results for the

bridgehead radicals in Table III is the large decrease

in selectivity compared to other acyclic and monocyclic

32aliphatic radicals. The decreased steric requirement

of the bridgehead radicals was suggested as one of the

key factors in the lessened selectivity of those

substances mentioned previously. However, it is

surprising to find that the least hindered radicals of

this groiap are the most selective. This can be explicable

by the variation of polar character in the transition

state of the bridgehead radicals for the halogen

abstraction reaction.

Table III

Bridgehead Radicals Selectivity in Halogen

Atom Abstraction Reactions

Radicals Hunsdiecker reaction. 80 C

0.14a'b

fRBr][RCl]

0.48b'c

0.52b

0.72d

1.00b|e

1.05a

(a) Ref. 32. (b) Ref. 33- (c) Ref. 41. (d) This study,

(e) Ref. 43.

(63)

Since chlorine atom is more electronegative than

bromine atom, electron transfer from bridgehead radical

to halogen atom is more favorable in (62). In addition,

the less strained bridgehead radicals would accommodate

the positive charge more readily because the carbenium

ions favor planar geometry. Consequently, less strained

bridgehead radicals give more chloro compound and

become less selective. These arguments may provide a

plausible explanation on the selectivity of bridgehead

radicals in the halogen abstraction reactions as observed

in this study and related reports.99 a

IV. SOLVOLYSIS OF 1-TRICYCLOt.2.1.0?' 6]oCTYLMETHYL TOSYLATE (64):

The solvolysis of the neopentyl derivatives leads to

products derived almost exclusively from a rearranged

carhenium ion or an equivalent intermediate. The timing of

the rearrangement step is of considerable interest and still

opens to controversy. Various groups have favored a concerted

mechanism. Evidence for this argument has been advanced on

44-47 n. .48-50the basis of the absence or only very small amount

of unrearranged products and almost complete inversion of

the migration terminus in a suitably deuterated substrate.

52-54It has been conceded, however, that a stepwise process

would yield similar experimental results, as long as

rearrangement step is fast. Most neopentyl-like rearrangements

have similar rate constants and the even included cases

where conversion of the primary carbenium ion into its

44-56tertiary analogue is expected to be relatively unfavorable.

It was suggested that the rate limiting step would be the

initial ionization and the rate differences could arise

49from inductive and steric effects. However, it was agreed

that, in cases where rearrangement relieves substantial amounts

of ring strain, the process may be concerted or nearly so.

Solvent participation is important in the solvolysis of

simple alkyl derivatives. However, neopentyl systems are

sterically hindered toward nucleophilic attack by solvent

48-51

molecules, although S2 type reactions have been known

•:59in neopentyl derivatives.' Relatively little is known

about medium effect on neopentyl solvolysis, which may have

been underestimated. It; is of interest to investigate the

solvent behavior in the acetolysis of 1-tricyclo [5.2.1.0-

octylmethyl tosylate (64).

The tosylate (64) can be prepared readily from 1-hydroxy-

methyltricycloL3•2.1.0? Joctane (50) by standard procedure

as mentioned previously.

The rates of acetolysis of (64) were measured in anhydrous

48-50 53 56acetic acid. e resu]_ts are summarized in Table IV.

The activation parameters were calculated and also listed in

Table IV.

Table IV

Rates of Acetolvsis cf 1-Tricvclo r?.2.i.o5,6]

octvlmethvl Tosylate (64)

Temperature °C

99.2

111

119

1.050.01

2.33+0.12

3.70+0.29

18.21.5 -32.7+O.I

The rate constants for a series of related neopentyl

solvolytic reactions are outlined in Table V for comparison.

As previously noted, most of rate constants are comparable.

That for the solvolysis of (64) is about six times greater

than that for neopentyl tosylate' and slightly smaller

(0.8 time) than that for 1-bicyclo2.2.1Jheptylmethyl

tosylate at 100 C.

Table V

Relative Rates of Solvolysis of Bridgehead

Carbinyl Tosylate at 100 C

Compounds

(CH5)5CCH2OTs

R e 1. k

a1 .00

b1.3

c

5.5

, d6.7

189.7 6

a). Ref. 56. b). Ref. 49- 0- This study,

d). Ref. 55. e). Ref. 48.

It, is noteworthy that the more strained tosylate (64) reacts

even slower than the less strained norbornyl derivative. It

is particularly interesting to note that the enthalpy of

activation for (64) is somewhat lower than that for related

49systems, and the entropy of activation is much more

49negative than that for other neopentyl derivatives. The

entropy of activation has widely been used as the criterion

65

to distinguish between S,T1 and S„2 processes. Therefore,N N

the large negative entropy of activation for the acetolysis

Of (64) suggests that significant amount of the reaction

may proceed bimolecularly. In other words, nucleophilic

solvent attack on neutral substrate (64) or the corresponding

tight ion-pair (67) may play an important role during the

course of reaction.

This argument agrees well to our result on the product

distribution. Thus, the tosylate (64) was refluxed with

anhydrous acetic acid to give the unrearranged acetate (65)

(34) and the ring expansion product (66) (47%) in addition

to three rearranged minor products whose structures were

not clear. The yield of the primary acetate (65) was unusually

high comparing with known examples. In the previous studies,

the acetolyses of bicyclo [2.1 .l] hexylmethyl tosylate and

49adamantylmethyl tosylate afforded the unrearranged products

(68) and (69) in 2% and 6.8%, respectively. Such discrepancy

is really striking. The relief of steric strain and the form

ation of more stable tertiary carbenium ion. were believed

to be the driving force of the Wagner-Meerwein rearrangement

of the neopenfyl-type system. The difference in strain energy»

between (69) and (66) would be of the order of 1 Kcal on

the basis of the difference of the calculated strain energy

between the respective hydrocarbons. Moreover, the

bridgehead carbenium ion (70)» which is formed from the

rearrangement of the tight ion-pair (67) and will lead to

the product (66), is significantly distorted from planar

structure and. is thus highly unstable. Therefore, the

rearrangement process seems not so favorable in (64) and

the nucleophilic solvent attack would become apparent,

which resulted in increasing yield of (65). Hence, this

tricyclooctane system would be more susceptible to such

nucleophilic attack on because the environment about

in (64) is less sterically hindered than simple

neopentyl counterpart at the reaction site.

Furthermore, the reaction of 1-hydroxymethyltricyclo-

[3 .2.1.0'octane (50) in thionyl chloride at room

temperature afforded only the unrearranged chloride (71)

in 620 yield.

Thus, it revealed that the rearrangement of this tricyclooctane

system might not be a facile process under these mild

conditions. This observation is also in agreement with our

proposal described early in this section.

The nature of neighboring group participation in the

solvolysis of (64) is not clear. However, no internal

return rearranged product (72) was obtained in this study.

This indicates that the ionization step may proceed without

neighboring group participation. In other words, rearrange¬

ment may occur only after the formation of solvent seperated

ion pair (73) or an equivalent entity. The plausible mechanism

for the solvolysis of (64) is outlined in Scheme Y.

In summary, we have described the direct observation of

solvent participation in solvolysis of a neopentyl derivative.

This system is, to the best of our knowledge, the first

SCHEME V

instance amongthe non-heterocyclic neopenty1-like examples (74)?

which exhibits significant nucleophilic solvent assistance

in the solvolytic reactions..

Compound (74) has been found to solvolyze without rearrangement

in dilute hydrochloric acid at a very slow rate due to the

6 2positively charged nitrogen atom.

EXPERIMENTAL

Nuclear magnetic resonance (pmr) spectra were obtained

1 5using JEOL 60-HL Spectrometer (60 MHz). C-nmr spectra

were recorded on a JEOL FX90Q, NMR Spectrometer. Infrared

(ir) spectra were measured on a Perkin-Elmer 283 Infrared

Spectrophotometer, Mass spectra (ms) were determined on a

Vg-7070F Mass Spectrometer. Microanalyses were performed

by the Australian Microanalytical Service, Melbourne.

Melting points (mp) and boiling points (bp) are uncorrected.

Diphenyl diselenide

Diphenyl diselenide was prepared according to literature

method, and the product was recrystallized from

C

methanol before used; mp. 63-64r 22 C1Llit. 63.5 J

2-Allyl-2- carboethoxycyclopentanone (29)

Potassium tertiary butoxide (270 g, 2.4 mol) was mixed

with N,N-dimethyl formamide (1L) to which 2-carboethoxy-

cyclopentanone (312 g, 2 mol) was added under external

cooling (ca. 10°c). Allyl bromide (290 g, 2.4 mol) was then

added dropwise in 2h at 0°C. After the addition was complete,

the mixture was stirred at room temperature for 38h, and

poured onto ice-water mixture, and it was extracted with

diethyl ether (5x500 mL). The combined etheral solution

was washed with water (2x1L), brine solution (1L), dried

over anhydrous magnesium sulfate, filtered, and evaporated

in vacuo, the residue was fractionally distilled to give

5-Allyl-5- carboethoxy-2-cyclopentenone( 25)

Tetrahydrofuran (500mL) was directly distilled under

nitrogen into a 2-L three-necked round bottomed flask,

Diisopropylamine (58.8 mL, 0.274 mol, freshly distilled

from calcium hydride), n-butyl lithium in ether (1.14 M,

240 mL, 0.274 mol), and a mixture of 2-allyl-2-carboethoxy-

cyclopentanone (29) (49 g, 0.25 mol) and hexamethylphosphoric

triamide (88 g, 0.5 mol, freshly distilled from anhydrous

x Obarium oxide) were added in sequence at -78 C. The mixture

(29) (338.2 g, 8656; bp 50-52° [0.1 mm}; lit.17 bp 125

£l 1 mmj); ir (neat) s 170 (CO), 1752 (ester, CO), 1646

(c=c) cm1; pmr (CDCl) 61.21 (3H, t, J=6.7 Hz), 1.57-2.83

(8H, m), 4.10 (2H, q, J=6.7 Hz), 4-84-6.01 (3H, m)ppm;

15C-nmr (CDC1) 513-4 (CH,), 18.9 (C-3), 31-5 (C-4), 37-1

(C-2 or C-9), 37-3 (C-2 or C-9), 59.2 (C-5), 60.6 (CHgO),

118.1 (C=C, terminal), 132.7 (C=C), 170.1 (CO, ester),

215-2 (CO)ppm.

was stirred for 1h at -78 C. Then a solution of benzene-

selenenyl bromide in ether (2.24 M, 125 mL, 0.28 mol,

prepared from diphenyl diselenide(. 45• 7 g 0.14 molj and

bromine 22.4 g, 0.14 mol in dry ether ($25 mL]) was

added in one-portion and stirred for an additional 15 min.

Then hydrochloric acid (1 N, 500 mL) was added and the

mixture was extracted with ether (5500 mL). The combined

organic layers were washed with hydrochloric acid (1 N, 500

mL), sodium bicarbonate solution (5$» 500 mL), water (4x500

mL), brine solution (500 mL), and dried over anhydrous

magnesium sulfate, filtered, and evaporated to give a

brown residue (96.5 g)•

The brown residue (96.5 g) was dissolved in tetrahydro-

furan (600 mL) to which hydrogen peroxide (52$, 252 g, 2.57

mol) in tetrahydrofuran (240 mL) was added slowly at 0 C

over a period of 2h. The mixture was stirred at room

temperature for 8h. Water (1L) was added and extracted with

ether (5500 mL). The etheral solution was washed with

water (21L), brine solution (400 mL), dried over anhydrous

magnesium sulfate, filtered and evaporated in vacuo to give

a brown residue (56 g) which was passed through silica gel

(60 g) eluted with benzene. Further purification by spinning

band distillation gave (25) (7-4 g» 36$ based on recovered

starting material; bp 90-92°C [6mm); ir (neat)j): 1748 (CO,

ester), 1717 (CO), 1646 (C=C, allyl), 1597 (C=C, cyclopent-

—1

enone) cm; pmr (CDC1) Sl.20 (3H, t, J=7.2 Hz), 2.27-3.41

(4H, m), 4-08 (2H, q, J=7-2 Hz), 4.82-5.99 (3H, m), 6.10

(1H, d, t, J1=6 Hz, J2=1.8 Hz), 7-71 (1H, d, t, J =6 Hz,

J2=3 Hz) ppm; C-nmr (CDCl) $14.0 (CH,), 38.5 (C-4 or C-6),

38.7 (C—4 or C-6), 57.3 (C-5), 61.6 (CHgO), 119-1 (t,

terminal carbon of allylic C=C), 152.1 (C-3 or C-7) 152.7

(C-3 or C-7), 163.9 (C-2), 170-3 (GO, ester), 205.2 (CO) ppm;

mss me 194.

Anal. Calcd for C, 68.02; H, 7-26. Found:11 14 5

C, 68.49; H, 1,22.

1-Carboethoxytricyclo (3 ,2.1.0'3octan-2-one (24) and

1-carboethoxytricyclo C5-2.1.O,3octan~7~one (25)

A solution of 5-allyl-5-carboethoxy-2-cyclopentenone

(23) (1 .5 g, 7.7 mmo 1) in tetrahydrofuran (550 mL) was

irradiated (400W, medium pressure, mercury arc lamp, Applied

Photophysics 400LQ) under nitrogen at 0 C for 2-3h in a

pyrex photochemical reactor. The percentage of conversioni

was analyzed by gas chromatography. The solvent was

evaporated in vacuo, the residue was distilled to afford

a mixture of isomers (24) and (25) (1.07 g» 71%» ca. 10:1;

bp 83-85° C (o.06mm Hg)), ir (neat)): 1760 (CO), 1732 (CO,

•• 1

ester) cm, pmr (CDC1) $1.28 (3H, t, J=7.2 Hz), 1.53-2.80

(8H, m), 3.23 (1H, m), 4.22 (2H, q, J=7.2 Hz) ppm; C-nmr

spectral data for (24) s £l 4.2 (CH), 54.6 (C-5), 36.0 (C-4),

38.8 and 40.4 (C-7 and C-8), 40.9 (C-6), 45.2 (C-3), 60.9

(CHO), 65.8 (C-1), 169.9 (CO, ester), 210.9 (CO)ppm;

C-nmr spectral data for (25): S 30.1 (C-3 and C-5)» 36.0

(C-2 and C-8), 36.4 (C-4)» 42.4 (C-6), 61.2 (CHgOj-and the

Thiolketals (48) and (49)

To boron trifluoride etherate complex (10 ml), the

isomeric mixture of 1-carboethoxytricyclo (3• 2 .1 .0' octan-

2-one (24) and 1 -carboethoxytricyclo (3. 2 .1 .0' octan-7-one

(25) (7.5 Si 59 mmol) in dry ether (80 mL) was added at 0 C.

Methyl mercaptan (6 mL, 108 mmol, condensed at -78 c) was

added, and the mixture was stirred for 2h at room temperature.

Then it was poured into sodium hydroxide solution (10%, 100 mL).

The ether layer was seperated and washed with sodium hydroxide

solution (10%, 2100 mL), water (2x100 mL'), dried over anhydrous

magnesium sulfate, filtered and evaporated in vacuo. The

signals for C-1, two carbonyl carbons and CH-, were not5

observed and may be embodied in the absorption for (24);

ms: me 194.

residue was distilled to give a mixture of (48) and (49)

(9.02 g, 85$; bp 105-1100 [0.05 mm]); ir (neat) p: 1732

(ester, CO) cm pmr (CDCl) 1.26 (3H, t, J=7.0 Hz),

1 .48-2.56 (15H, m, embodied two singlets at 1.88 and 1 .99)9

4.08 (2H, q, J=7.0 Hz) ppm; ms: me 272.

1-Carboethoxytricyclo[5.2.1.0] octane In)

The isomeric mixture of the thiolketals (48) and (49)

(2.0 g, 7 .55 mmol) in absolute ethanol was heated under

reflux With an excess of W-2 Raney nickel catalyst (50 g)

for 4h. The catalyst was filtered and washed thoroughly

with ethanol (200 mL), ana then with benzene (500 mL). The

solvent was removed by evaporation in vacuo to afford a

residue which was distilled to give (15) (1.2 g, 91$;

bp 120-124 C [20mm]); ir (neat): j=1735 cm (CO); pmr

(CDGl) £1.24 (4H, t, CH embodied a multiplet 1H), 1.62

(2H, broad s), 1.71-2.56 (7H, m, embodied a broad s at 1.81),

2.85 (1H, m), 4.08 (2H, q) ppm; 1C-nmr (CDCl) f 14• 2 (CH),

54.6 (C-3 and C-5), 35.9 (0-4), 41.0 (C-2 and Q-8), 43-2

(C-6), 44.0 (0-7), 53.1 (C-1), 59.9 (CH20), 175.3 (CO) ppm;

ms: me 180.1167 (calcd for CHO 180.1150).

i-Hydroxymethyltricyclo[5.2.1. 0' ]octane Alo)

A solution of 1-carboethoxytricyclo[3•2.1.0'octane

(15) (1 -07 g 5-94 mmol) in tetrahydrofuran (10 mL, distilled

from lithium aluminium hydride) was added to a slurry of

lithium aluminium hydride (2 g, 52.7 mmol) in tetrahydrofuran

(30 mL) under nitrogen at 06C. It was stirred at 0°G for an

additional 4h and then at room temperature for 48h. Sodium

sulfate 'solution (10j£, 30 raf) was then added, and solid was

filtered. The solid was washed thoroughly with diethyl ether.

The aqueous layer was extracted with ether (320 mL). The

combined etheral extracts were washed with water (50 mL),

dried over anhydrous magnesium sulfate, filtered, evaporated

and distilled to give (50) (0 •73 g, 890; bp 112-114c [20mm]);

ir (neat): V =3%8 cm-1 (OH); pmr (CDCl) £1.14-1.70 (8H, m,

embodied two singlets at 1.29 and 1.54), 1.94-2.48 (5H, m),

2.79 (1H, m), 576 (2H, s) ppm; C-nmr (CDCl,) £34.8 (C-3 and

C-5), 35-9 (G—4), 40.0 (c-2 and C-8), 42.0 (C-7), 43-0 (C-6),

50.9 (C— 1), 66.3 (CHpO) ppm; ms: me 138.1110 (calcd for

CqH140: 138.1045).

1-TricycloC5.2.1.0' joctylmethyl tosylate Am)

Tosyl chloride (1 g, 524 mmol) was added to a mixture

of 1-hydroxymethyltricyclo [3 .2.1.0'octane (50) (500 mg,

1.97 mmol) in pyridine (7»0 g, 89 mmol, distilled from calcium

)0 at 0 G. The mixture was stirred at room temperature

for five days. It was poured into hydrochloric acid (3N, 100 mL)

and extracted with carbon tetrachloride (2X100 mL). The

combined organic extracts were dried over anhydrous magnesium

sulfate, filtered, and evaporated in vacuo. The residue was

seperated by column chromatography on alumina (basic, EM 1076,

15 g) first eluted with petroleum ether (50-75 C) to recover

the starting alcohol (50) (100 mg), and then eluted with

chloroformpetroleum (1 s 1) to give the tosyl derivative (64)

(92.8 mg, 46io based on unrecovered starting material); pmr

(CDC1)$ 0.70-1.90 (7H, m), 2.10-2.54 (6H, m), 2.82 (1H, m),

4.22 (2H, s), 7.75 (4H, m).

r iTricycloL3.2,1,0' Joctane-1-carboxylic acid (15)

3 61A solution of 1 -carboethoxytricyclo[$. 2 .1 .0' Joctane

(15) (l«3 g 7.22 mmol) in aqueous sodium hydroxide solution

(20$, 75 mL) was heated under reflux for 14h, cooled to room

temperature and washed with ether (200 mL). The aqueous

layer was seperated and neutralized with concentrated

hydrochloric acid (37$, 40 mL) while keeping the temperature

below 5°C. The mixture was then extracted with ether (3x250 mL).

The organic layer was washed with water (200 mL), dried over

anhydrous magnesium sulfate, filtered, and evaporated to

give a colorless solid which was sublimed to yield (1$)

(1.0 g, 91=; mp 106-107°c); ir (KBr:2955, 1696 (CO) cm-1;

pmr (CDC1) $1.10-1.35 (1H, m), 1.71 (2H, s), 1.82-2.71

(7H, mf embodied a singlet at 1 .91), 2.92 (1H, m), 11.92

(1H, s) ppm; 15C-nmr (CDCl) S 34.7 (C-3 and C-5), 35.8

(C-4), 40.9 (C-2 and C-8), 43-4 (C-6), 44.2(c-7), 52.9 (C-1),

182.5 (CO) ppm; ms: me 152.0823 (calcd for 0122''

152.0837).

Anal. Calcd for CH-] 22' 71-03; 795. Found:i.

c, 71.57; h, 8.oo.

1-Tricyclo[3.2,1.0' ctyl amine hydrochloride (52)

A solution of triethylamine (174-9 mg, 1.73 mmol) in

acetone (2.8 mL) was added dropwise to a solution of

tricyclo [3•2.1.0' J octane-1-carboxylic acid (13) (200 mg,

1.32 mmol) in acetone (2.8 mL) and water (0.3 mL) at 0 C.

Ethyl chloroformate (176.2 mg, 1.74 mmol) in acetone (1 mL)

was added dropwise and then stirred for 30 min. A solution of

sodium azide (135 mg, 2.08 mmol) in water (0.6 mL) was

subsequently added and stirred for 2h at 0 C. It was poured

onto ice-water and extracted with chloroform (4x20 mL). The

organic solution was dried over anhydrous sodium sulfate,

filtered, and evaporated to give crude azide (53) (240 mg,

m-Jp=2140 cm) as a yellow oil.

The crude azide (53) in benzene (35 niL) was refluxed for

1h, and benzene was removed by distillation at normal pressure

to give a yellow oil (200 mg) as the crude isocyanate (54)

(i=2280 cm-1).

The crude isocyanate (54) in tetrahydrofuran (10 mL) was

refluxed to which concentrated hydrochloric acid (32%, 5 mL)

was added for 1h and cooled to room temperature and diluted

with water (50 mL), and then washed with ether (2x50 mL).

The aqueous layer was seperated and evaporated in vacuo to

give a colorless solid which was recrystallized from acetone-

methanol to yield (52) (150 mg, 71%; mp 225°C [dec.]); pmr

(DMS0-d6) S1.17-1.27 (1H, m), 1.43-2.38 (9H, m, embodied two

singlets at 1.63 and 1.80), 2.78 (1H, m), 8.73 (3H, broad s) ppm;

15C-nmr (DMSO-dg) $33.6 (C-5 and C-5), 34.4 (C-4), 40.0 (C-2

and C-8), 40.3 (C-6), 41.8 (C-7), 60.0 (C-1) ppm; ms: me

123.1044 (M+-HC1, oalod for CgHN: 123.1048).

1-Bromotricyclo[3.2.1.0 loctane (37)

Tricyclo [3.2.1.0'Joctane-1-carboxylic acid (13) (200

1.52 mmol) and red mercuric oxide (286 mg, 1.32 mmol) in

O

dibromomethane (50 mL) was heated to 80 C and bromine (300 mg,

1.88mmol) was added dropwise and the mixture was refluxed for

2h. Dibromomethane was removed by distillation, n-pentane (200 mL)

was added, and the pentane solution was washed with 1OjS of

sodium hydroxide solution (50 mL), dried over anhydrous magnesium

sulfate, filtered, evaporated and purified by molecular

distillation to give a colorless oil and further purified by

preparative gas chromatography (60 C, 6 FT, SIL. GUM, GE.

XE-60 ON 60-70W AW, DMCS) to give pure bromide (57) (170 mg, 69%);

pmr (CDCl) $1.29-1.59 (1H, m), 1.55 (2H, s), 1.87 (2H, s),

2.08-2.45 (5H, m), 2.71 (1H, m) ppm; 5C-nmr (CDC1 )J35.3

(C-3 and C-5), 36.1 (c-4), 40.8 (C-2 and C-8), 48.3 (C-6),

49.4 (C-7), 60.1 (C-1) ppm; ms; me 186.0065, 188.0033

(oalcd for CgH Br7: 186.0044. calcd for CgHBr: 188.0024).

1-Chlorotricyclo[3.2.1,0]octane (58)

2 C

Tricyclo [3.2.1.0' ]octane-1-carboxylic acid (13) (100 mg,

0.66 mmol) and red mercuric oxide (150 mg, 0.69 mmol) in

carbon tetrachloride (20 mL, distilled from POq) was heated

to 80° C and bromine (160 mg, 1 mmol) in carbon tetrachloride

(5 mL) was added dropwise. The mixture was refluxed for 2h,

then cooled, filtered, evaporated to give a colorless oil which

was a mixture of the bromide (57) and the chloride (58) in a

ratio of 14 to 86 as exhibited on the gas chromatogram. pure

(58) was obtained by preparative gas chromatography (60 C, 6 FT,

1% SIL. GUM. GE XE-60, ON 60-70W. AW. DMCS) as colorless liquid

(60 mg, 61?6); pmr (CDCl) $1.30 (1H, m), 1.54( 2H, s), 1 .78

(2H, s), 1.99-2.41 (5H, m), 2.78 (1H, m) ppm; ms: me 142.0520,

144.0421 (calod for CqHCI55: 142.0549; calcd for CgHCl57:

144.0519).

Selectivity Study of Hunskiecker Reaction of _Lii)

The carboxylic acid (13) (50.6 mg, 0.33 mmol), mercuric

oxide (red, 71-3 mg, 0.33 mmol) in carbon tetrachloride

©

(5•06 g, 33 mmol) was heated to 80 C and then bromine (17 JLL,

0.33 mmol) was added with a microsyringe. The mixture was

refluxed for 1h, and then cooled, filtered, and washed with

carbon tetrachloride (7 mL). The combined organic solution was

washed with sodium hydroxide solution (107$, 10 mL), dried over

anhydrous magnesium sulfate, filtered, and evaporated in vacuo.

The distribution of products was analyzed by gas chromatography

(60 C, 6 FT, 1o SIL. GUM. GE XE-60 ON 60-70W. AW. DMCS).

Analysis of the reaction mixture indicated that the bromide

(37) and chloride (58) were produced in a ratio of 42 to 58,

respectively.

The pKa measurement

(A). 50( v) methanol-water.

The CHEMTRIX TYPE 60A pH meter with BJC pH electrode was

employed for pH measurements. Sodium hydroxide solution was

prepared by dilution of 0.1N aqueous sodium hydroxide solution

with equal volume of methanol, and it was standardized against

potassium acid phthalate. The method was checked by the

35determination of the pKa of benzoic acid. The carboxyiic acid

(13) was dissolved in 5 0% (v) methanol-wat er and titrated with

the standardised sodium hydroxide solution. After each increment

of base was added the solution was stirred for 45 sec followed

by a waiting period of 1 min before the meter was read. The

pKa of the carboxyiic acid (13) was determined by the expression

at 50% neutralization. The results are

summarized in Table VI.

(B). 5¥( w) ethanol-watex-.

The procedure was followed as described before except that

50% (v) methanol-water was replaced by 50% (w) ethanol-water.

The results are listed in Table VII.

Table VI

The pKa of 1-Tricyclo[3.2.1.0'octane-carboxylic

acid (13) in 5 (v) methanol-water at 25 C

Substrate

Benzoic

acid (g)

0.0129

0.0102

Carboxylic

acid (15) (g)

0.0099

0.0078

Sodium Hydroxide Solution

Added at Ofo Neutralization

(mL)a

11 .52

9.10

7.08

5.60

pH observed pKa

5.28t

5.28

5.28

5.28

5.89

5.89

5.89

5.89

-5(a) The concentration of base was 4.5914X10... N.

(b) Ref. 35.

Table VII

The pKa of 1-Tricyclo [3.2.1.0'octane-carboxylic

acid (13) in 50J (w) ethanol-water at 25°C

Substrate

Benzoic

acid (g)

0.0093

0.0088

Carboxylic

acid (13) (g)

0.0102

0.0099

Sodium Hydroxide Solution

Added at neutralization

(mL)a

pH observed pKa.

5-76b

5.76

5.76

5.76

5.76

5-44

5.06

4.92

6.52

6.52

6.52

6.52

-3

(a)The concentration of base was 6.6274X10 N.

(b) Ref. 36.

1 r f) t

Bate of Acetolysis of 1-TricycloL5 .2.1.0' Joctylmethyl Tosylate 164)

The acetolysis was conducted in anhydrous acetic acid

63according to the method of Winstein, Grunwald, and Ingraham.

Anhydrous acetic acid was prepared by adding sufficient

acetic anhydride to react, with the water present in glacial

acetic acid. The mixture was refluxed for 3h, distilled, and

63the distillate was stored in desiccator before used.

Approximately 0.01N perchloric acid in acetic acid was

prepared by dilution of a 72rfo aqueous solution with the

anhydrous acid. This solution was standardized against

potassium acid phthalate to a bromphenol blue end point.

-3Approximately 5x10 N sodium acetate in acetic acid was

prepared by the addition of anhydrous sodium carbonate to

the anhydrous acid and was standardized against perchloric

acid solution. In all titrations, eight drops of bromphenol

blue indicator in the anhydrous acid were used per 3

solution.

The acetolysis was conducted as follow: 4 mL aliquots

of a 6.356X10% solution of the tosyl derivative (64) in

the anhydrous acid were placed in ampoules, which were placed

• «

in three constant temperature baths at 99•2x0.1 C, 111 C.

1190, respectively, single ampoules removed at selected

time intervals, immediately cooled, opened, 3-00 mL aliquots

was pipetted, and titrated against the sodium acetate solution.

The time was computed from the time of opening the ampoules.

The first order rate constants were calculated from the

expression kt= In. (aa-x). The results are summarized in

Tables VIII, IX, and X.

Table VIII

Rate of Acetolysis of tosylate (64) at 99.2t0.Tc

Time, ..sec.

23520

43200

69480

(a-x)x105, Ma

6.080

4.988

3.062

kx10 sec''

1.030

1.059

1.051b

Table IX

Rate of Acetolysis of tosylate (64) at 111 C

Time, sec (a-x)x10, M5 -1

kx10, sec

43290

69524

100590

2.272

1 .178

0.698

2.376

2.425

2.195°

Table X

O

Rate of Acetolysis of tosylate (64) at 119 C

Time, sec

5970

25870

(a-x)xlO5, M

5.054

2.759

kx10, sec

5.905

5-496d

Product Distribution Determination of Acetolysis of Tosylate Am)

Two 25-mg samples of 1 -tricyclo[5• 2 .1. 0 9 octylmethyl

tosyl ate (-64) were placed in two ampoules each containing

5 mL of anhydrous acetic acid. The ampoules were placed in

O

a bath at 119 C for 50h. They were then cooled, opened, and

poured into water. The mixture was extracted with ether. The

ether layer was washed with water, dried over anhydrous

magnesium sulfate, filtered, and evaporated in vacuo. Analysis

of the residue by gas chromatographic method indicated that

the unrearranged acetate (65) and the rearranged acetate (66)

were produced in 57 and 47 respectively, in addition

to three rearranged, minor products whose structures were

not clear. The unrearranged acetate (65) exhibited a singlet

at $416 (CHOAc) in the pmr spectrum and £66.8 (CHOAc) in

1 3addition to eight other absorptions in C-nmr spectrum.

The rearranged acetate (66) showed no absorption below

in pmr spectrum and S 79•9 (C-OAc) and eight other signals

13in C-nmr spectrum.

1-Chioromethyltricyclop.2.1octane .in)

1-Hydroxymet'hyltricyc lo [3• 2 .1. 0' octane (50) (138 m£

1 mmol) was stirred with thionyl chloride (2.5 mL, 34-3 mmol)

at room temperature for 22h. The mixture was poured onto

ice, and then extracted with ether (3x25 mL). The combined

etheral solution was washed with saturated sodium bicarbonate

solution (2x50 mL), water (50 mL), dried over anhydrous

magnesium sulfate, filtered, and evaporated.-The residue was

purified by column chromatography on alumina (basic, 10 g)

o

eluted with petroleum ether (50-75 C) to give (71)

(96 mg, 62°jo) pmr (CDCl)£ 1.12-1.42 (4H m), 1 .46-1 .80 (3H,

m, embodied a singlet at 1.53) 2.04-2.44 (3H, m), 2.76

1 3

(1H,. m), 4.O6 (2H, an AB system, J=10.2 Hz) ppm; C-nmr

(CDC15) S 34.9 (c-3 and C-5), 35.9 (C-4), 40.5 (C-2 and C-8),

42.6 (C-7), 43.1 (C-6), 48.8 (C-1), 65.4 (CHgCl) ppm;

ms: highest me 121 (M+-Cl).

REFERENCES

1. A. Greenberg and J. F. Liebman, Strained Organic Molecules,

Academic Press, N. Y. 1978.

2. A. Greenberg and J. F. Liebman, Chem. Rev., 16, 311 (1976).

3. R. R. Sauers, R. A. Parent, and S. B. Damle, J. Am. Chem. Soc.,

88, 2257 (1966).

4. R. R. Sauers and R. J. Kiesel, J, Am. Chem. Soc., 89

4095 (1967).

5. S. A. Monti and S. S. Yuan, Tetrahedron Lett., 3627 (1969).

6. J. M. Harless and S. A. Monti, J. Am. Chem. Soc., 16,

4717 (1974).

7. S. A. Monti and J. M. Harless, J. Am. Chem. Soc., 99»

2690 (1977).

8. M. Geisel, C. A. Grob, W. Santi, and W. Tschudi, Helv.

Chim. Acta.. 56,1055 (1973).

9. P. K. Freeman, R.B. Kinnel, and T. D. Ziebarth, Tetrahedron

Lett., 1059 (1970).

10. (a) P.v.R. Schleyer and R. C. Fort, Jr., Adv. Alicyclic•S

Chem., 283 (1966);

(b) R. C. Fort, Jr., Adamantane. The Chemistry of Diamond

Molecules, Marcel Belcker, N.Y. 1976.

(c) R, C. Fort, Jr., in Carbonium ions G. A. Olah and

P.v.R. Schleyer, eds., Vol. IV, John Wiley Sons, Inc.,

(1973)» Chapter 32.

11. R. B. Woodward and R. Hoffmann, The Conservation of

Orbital Symmetry, Academic Press (1970)•

12. P. Grabbe, G. A. Garcia,and E. Velarde, Chem. Commun.,

480 (1973).

13. M. Mellor, D. A. Otieno, and G. Pattenden, Chem. Commun.,

138 (1978).

14- W. Frostl and P. Margaretha, Helv. Chim. Acta., 39»

2244 (1976).

15. P- S. Pinkney, Org. Syn. Coll. Vol. II, p 116 (1962).

16. V. M. Micovic, Org. Syn. Coll. Vol. II, p 264 (1962).

17. H. Staudinger and L. Ruzicka, Helv. Chim. Acta., 7

446 (1924).

18. (a) E. A. Braude and E. A. Evans, J. Chem. Soc.., 607 (1954)»

(b) R. Joly, J. Warnant, G. Namine, and D. Bertin,

Bull. Soc. Chim. Fr, 366 (1958);

(c) E. W. Garbisch, Jr., J. Org. Chem. 30, 2109 (1965);

(d) P. L. Stotte and K. L. Hill, ibid., 38, 2576 (1973)»

(e) B..Miller and H.. S. Wong, Tetrahedron, 28, 2369 (1972);

(f) M. E. McEntee and A. R. Pinder, J. Chem. Soc., 4419

(1957);

(g) C. W. T. Hussey and A. R. Pinder, ibid., 3525 (1.961);

1517 (1962);

(h) J. E. Brenner, J. Org. Chem., 26, 22 (1961).

19 (a) R. J. Theissen, J. Org. Chem., 56, 752 (1971)5

(t) D. Walker and J. B. Hiebert, Chem. Rev., 6_7, 153 (1967);

(c) T. Cohen, C. K. Shaw, and J. A. Jenkins, J. Org, Chem.,

38, 3737 (1973);

(d) r. A. Jerusi, Sel. Or. Transform., 1_, 301 (1970) J

(e) J. N. Marx, J. H. Cox, and L.R. Norman, J. Org. Chem.,

37, 4489 (1972);

(f) A. F. Thomas and M. Ozainne, Chem. Commun., 746 (1973).

20. J. S. Sheehan and C. Mumaw, J. Am. Chem. Soc., 72, 2127

(1950).

21. B. L. J. Clive, Tetrahedron, 34, 1049 (1978), and references

therein.

22. H. J. Reich, J. M. Renga, and I. L. Reich, J. Am. Chem. Soc.,

97, 5434 (1975).

23. N. Ikota and B. Ganem, J. Org. Chem., 43, 1607 (1978).

24. P. de. Mayo, Accounts Chem. Research, 4,41 (1971)•

25. E. J. Corey, J. B. Bass, R. LeMahieu, and R. B. Mitra,

J. Am. Chem. Soc., 86, 5570 (1964)•

26. L. F. Fieser, J. Am. Chem. Soc., 76, 1945 (1954).

27• F. Sondheimer and B. Rosennthal, J. Am. Chem. Soc., 80,

3995 (1958).

28. Y. Permutli, N. Baniels, and Y. Mazur, Tetrahedron, 24,

5425 (1968).

29. G. P. Pettit, Org. Reactions, 12, 410 (1962).

30. D. G. Morris and A. M. Murray, J. Chem. Soc. Perkin II.,

734 (1975).

31. C. Kaiser and J. Weinstock, Org. Syn., 51, 48 (1971)-

32. T. Y. Luh and L. M. Stock, J. Org. Chem., 43, 3271 (1978).

33 K. Herwig and C. Riichardt, Chem. Ber., 105, 363 (1972).

34. G. S. Poindexter and P. J. Kropp, J. Org. Chem., 41» 1215

(1976).

35. R. Kuhn and A. Wassermann, Helv. Chim. Acta., 11, 1 (1928).

36. E. Grunwald and B. J. Berkowitz, J. Am. Chem. Soc., 75 t

4939 (1951).

37. H. D. Holtz and L. M. Stock, J. Am. Chem. Soc., 86, 5188 (1964).

38. C. F. Wilcox and C. Leung, J. Am Chem. Soc., 90. 336 (1968).

39. L. M. Stock, J. Chem. Ed., 49, 400 (1972).

40. T. W. Cole, Jr., C. J, Mayers, and L. M. Stock, J. Am. Cfoem.

Soc., 96, 4555 (1974) a,nd references therein.

41 K. Herwig, P. Lorenz, and C. Ruchardt, Chem. Ber., 108,

1421 (19.75) and references therein.

42. F. W. Baker, H, B. Holtz, and L. M. Stock, J. Org. Chem.,

28, 514 (1963).

43. G. L. Dunn, V. J. DePasquo, and J. R. S. Hoover, J. Org. Chem.,

13, 1454 (1968).

44. C. A. Grob, M. Ohta, E. Renk, and A. Weiss, Helv. Chim, Acta.,

41, 1191 (1958).

68

45. G. M. Farser and H. M. R. Hoffmann, Chem. Commun., 561 (1967).

46. G. Solladie, M. Muskatirovic, and H. S. Mosher, ibid.,

809, (1968).

47. W. G. Dauben, J. L. Chitwood, and K. V. Scherer, J. Am.

Chem. Soc., 90, 1014 (1968).

48. K. B. Wiberg and B. R. Lowry, ibid,,85, 3188 (1963).

4.9. J. E.Nordlander, S. P. Jindal, P. v. R. Schleyer, R. C. Fort,

Jr., J. J. Harper, and R. D. Nicholas, ibid,,88, 4475 (1966).

50. J. C. Fairlie, R. McCrindle, and R. D. H. Murray,

J. Chem. Soc. (C) 2115 (1968).

51. S. H. Liggero, R. Sustmann, and P. v. R. Schlayer,

J. Am. Chem. Soc., 21, 4571 (1969).

52. W. A. Saunderson and H. S. Mosher, ibid., 88, 4185 (1966).

53. W. M. Schubert and W. L. Hensen, ibid., 6299 (1971)-

54. J. W Wilt, C. T. Parsons, C. A. Schneider, D. G. Schultenover,

S. J. Wagner, and W. J. Wagner, J. Org. Chem., 33, 694 (1968).

55. R. L. Bixler and C. Niemann, ibid., 239 742 (1958)..

56. S. Winstein, B. K. Morse, E. Grunwald, K. C. Schreiber,

and J. Corse, J.Am. Chem. Soc., 74, 113 (1952).

57. J. M. Harris, Prog. Phys. Or g. Chem., 11, 89 (1974)•

58. T. W. Bentley and P. v. R. Schleyer, Ady. Phys. Org.Chem.,

14, 1 (1977).

6959. (a) B. Stephenson, G. Solladie, and H. S. Mosher, Jam.

Chem. Soc., 94, 4184 (1972).

(b) Y. Okamoto and T. Yano, Tetrahedron Lett., 4285 (1971).

(c) R. G. Weiss and E. I. Snyder, J. Or g. Chem., 36, 403

(1971)-

60. E. M. Engler, J. D. Andose, and P. v. R. Schleyer,

J. Am. Chem. Soc., 95, 8005 (1973).

61. M. R. Smith and J. M. Harris, J. Org. Chem., 43, 3568 (1978).

62. C. A. Grob, R. M. Hoegerle, and M. Ohta, Helv. Chim. Acta.,

45, 1823 (1962).

63. S. Winstein, E. Grunwald, and L. L. Ingraham, J. Am. Chem.

Soc., 70, 821 (1948).

64. (a) D. G. Taster, Org. Syn. Coll. Vol. III, 771 (1955).

(b) K. B. Sharpless and M. W. Young, J. Ora. Chem., 40,

947 (1975).

65. (a) C. K. Ingold, "Structure and Mechanism in Organic

Chemistry", 2nd ed., Cornell Univ. Press, Ithaca, N.Y.,

1969, p471

(b) G. Kohnstam in "The Transition State", Spec. Pubs.

Chem. Soc., 16, 179 (.1962)