Title: Synthetic and solvolytic studies in the endo, exo-bismethanonapthalene sic system
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Title: Synthetic and solvolytic studies in the endo, exo-bismethanonapthalene sic system
Physical Description: ix, 117 leaves : ill. ; 28 cm.
Language: English
Creator: Wallace, Benjamin, 1948-
Copyright Date: 1979
 Subjects
Subject: Bismethanonaphthalene   ( lcsh )
Solvolysis   ( lcsh )
Organic compounds -- Synthesis   ( lcsh )
Chemistry thesis Ph. D
Dissertations, Academic -- Chemistry -- UF
Genre: bibliography   ( marcgt )
non-fiction   ( marcgt )
 Notes
Statement of Responsibility: by Benjamin Wallace, Jr.
Thesis: Thesis (Ph. D.)--University of Florida, 1979.
Bibliography: Bibliography: leaves 113-116.
General Note: Typescript.
General Note: Vita.
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Bibliographic ID: UF00099253
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 - 000100370
oclc - 07390760
notis - AAL5831

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SYNTHETIC AND SOLVOLYTIC STUDIES IN THE
ENDO, EXO-BISMETHANONAPTHALENE SYSTEM



By

BENJAMIN WALLACE, JR.


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



UNIVERSITY OF FLORIDA

1979



































To My Parents















ACKNOWLEDGEMENTS


The author wishes to acknowledge the helpful

contributions, interest and guidance of Professor Merle

A. Battiste during the course of this research.

He also extends his sincerest thanks to Dr. Donna

McRitchie and Charles Gerhart for their technical assis-

tance and friendship. The author also wishes to express

his appreciation to the faculty of the Chemistry Department

in general, and especially the Organic Division, for their

patience and extra considerations during some most difficult

times. Finally, he wishes to extend a very special thanks

to Dr. John Zoltewicz and Dr. Merle Battiste, whose help,

patience, and perseverance, early in his graduate studies,

provided the major motivation for reaching this point in

his academic life.















TABLE OF CONTENTS


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

LIST OF TABLES........................................... V

LIST OF FIGURES.......................................... vi

ABSTRACT.... .............................................vii

CHAPTER

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

II SYNTHESIS AND CHEMISTRY............. ................. 18

III RESULTS AND DISCUSSION............... .............. 39

Kinetic and Product Results.... ...................... 39
Discussion........................................... 44

IV EXPERIMENTAL........................................ 52

Synthesis................................................. 53
Kinetic Studies..................................... 84
Solvolysis Product Studies .......................... 108

BIBLIOGRAPHY.... ............... ..........................113

BIOGRAPHICAL SKETCH....................................... 117
















LIST OF TABLES


Table

I Relative Yields of Adducts... .................... 11

II Rates of Acetolysis of Several Endo, Exo-
Bismethanonaphthalene Tosylates................... 40

III Identity and Relative Percentages of
Products from Acetolysis of several Endo,
Exo-Bismethanonaphthalene Tosylates.............. 41

IV Activation Parameters from Acetolysis of
Several Endo, Exo-Bismethanonaphthalene
Tosylates. ........................................ 42

V Comparison of Solvolytic Rates at 250C........... 43















LIST OF FIGURES


1 1Hnmr Spectrum of 12,12-dimethoxy-endo,
exo-anti-tetracyclo[6.2.1.13'6.02'/]dodec-
4-en-ll-ol (73)-OH................................. 29

2 1Hnmr Spectrum of 12,12-dimethoxy-endo,
exo, anti-tetracyclo[6.2.1.13',.02' 7 dodec-
4-en-ll-yl p-methylbenzenesulfonate (73)-OTs...... 30

3 1Hnmr Spectrum of syn-12-methoxyl-endo,
exo-anti-tetracyclo[6.2.1.13'6.02'7]dodec-
4-en-ll-ol (69)-OH............................... 31

4 Hnmr Spectrum of syn-12-methoxyl-endo,
exo-anti-tetracyclo[6.2.1.13'6.02' ]dodec-
4-en-ll-yl (69)-OSiEt ............................ 32

5 1Hnmr Spectrum of anti-12-methoxyl-endo,
exo-anti-tetracyclo[6.2.1.13'6.0 7]dodec-
4-en-ll-ol (70)-OH................................ 33

6 'Hnmr Spectrum of anti-12-methoxyl-endo,
exo-anti-tetracyclo[6.2.1.13'6.02'7]dodec-
4-en-ll-yl p-methylbenzenesulfonate
(70)-OTs ..... ............ ......................... 34

7 1Hnmr Spectrum of endo, exo-anti-tetracyclo-
[6.2.1.13'6.02'']dodec-4-en-12-one-ll-ol
(64)-OH ............... ........................... 35

8 Hnmr Spectrum of endo, exo-anti-tetracyclo-
[6.2.1.13'6.02'7]dodec-4-en-12-one-11-yl
p-methylbenzenesulfonate (64)-OTs................ 36

9 1IInmr Spectrum of 12,12-diethoxy-endo,
exo, anti-tetracyclo[6.2.1.13 ".0 7-
dodec-4-en-ll-ol (82)- 1 ........................... 37

10 IHnmr Spectrum of anti-12-ethoxy-endo,
exo-anti-tetracyclo[6.2..113'6.02'7]-
dodec-4-en-ll-ol (83)-OH............................. 38















Abstract of Dissertation Presented to the
Graduatc Council of the University of Florida
In Partial Fulfillment of the Requirements
for the Degroo of Doctor of Philosophy


SYNTHETIC AND SOLVOLYTIC STUDIES IN THE
ENDO, EXO-BISMETHANONAPHTHALENE SYSTEM


By


Benjamin Wallace, Jr.


December 1979



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


The activation of a carbon-carbon double bond in

cycloaddition reactions by through-space orbital interac-

tion with a non-bonding electron pair situated on a

proximate oxygen atom has been a topic of recent interest.

In order to probe the possibility of oxygen lone-pair

activation of a carbon-carbon double bond participation at

a developing ion center the syntheses and acetolyses of the

following p-methylbenzenesulfonates have been carried out:

12,12-dimethoxy-endo, exo-anti-tetracyclo[6.2.1.13'6.02'7]-

dodec-4-en-ll-yl p-methylbenzenesulfonate (I), anti-12-

methoxyl-endo, exo, anti-tetracyclo[6.2.1.1 3'.02'7]dodec-









4-en-ll-yl p-methylbenzenesulfonate (II), syn-12-methoxyl-

endo, exo-anti-tetracyclo[6.2.1.13'6.02'7]dodec-4-en-ll-yl

p-methylbenzenesulfonate (III), endo, exo, anti-tetracyclo-

[6.2.1.13'6.02'7]dodec-4-en-ll-yl p-methylbenzenesulfonate

(IV), and endo, exo-anti-tetracyclo[6.2.1.13'6.02'7]dodec-

4-en-12-one-ll-yl p-methylbenzenesulfonate (V).

The dimethoxy substituted sulfonate ester (I) was

shown to solvolyze at a rate which is 2.44 times faster

than the unsubstituted sulfonate ester (IV). Substrate (I)

also yielded two major products and one or more unidentified

minor products. Solvolysis through 5.4 half-lives produced

a product mixture that was comprised of 94% of endo, exo-

pentacyclo[6.3.1.03'10.04'12.05'9]dodeca-2-one-ll-yl methyl

ether (VI) and 6% of endo, exo, pentacyclo[6.3.1.03'10

.04'12.05'9]dodeca-2-one-ll-yl acetate (VII).

The synthesis of the syn-12-methoxyl sulfonate ester

(III) was primarily accomplished by reaction of (I)-OSiEt3

with a 4:1 molar mixture of aluminum chloride/lithium

aluminum hydride in ether. This reagent yielded a product

mixture containing 85% of (III)-OSiEt3 and 15% of (II)-OSiEt3.

Following chromatographic separation of the ethers and

desilylation with tetrabutylammonium fluoride, the resultant

alcohols were converted to their respective sulfonate esters.

The relative percentages of (II)-OSiEt3 and (III)-OSiEt3

could be reversed by changing the reagent to a 2:1.5 molar

mixture of anhydrous aluminum chloride/triethylsilane.


viii









The acetolysis rates of (II) and (III) at 250C were

approximately one-third that of the unsubstituted sulfonate

ester (IV), and clearly demonstrated the electron-withdrawing

properties of the methoxyl group. In contrast to what was

expected, the syn-methoxyl isomer (III) solvolyzed slower

than the dimethoxy ester (I) and was also slightly slower

than the anti-methoxyl isomer (II). Solvolysis of (III)

for 10 half-lives yielded a two product mixture composed of
3,6 4,12
85% of syn-2-methoxyl-endo, exo-pentacyclo[6.3.1.0 .04

.0 59]dodeca-ll-yl acetate and 15% of syn-2-methoxyl-endo,

exo-pentacyclo[6.3.1.O3'6.0 412.05'9]dodec-ll-yl-p-methyl-

benzenesulfonate. Solvolysis of (II) for 10 half-lives

yielded a two product mixture composed of 96% of anti-2-
3 6 a 12 5,9
methoxyl-endo, exo-pentacyclo[6.3.1.0 36.012 .0 59]dodeca-

11-yl acetate and 4% of anti-2-methoxyl-endo, exo-pentacyclo

[6.3.1.03'6.04'12.05',9dodeca-ll-yl p-methylbenzenesulfonate.

The rate enhancement in (7) was attributed to a combi-

nation of methoxyl participation in the transition state

and "orbital interactions through bond and space" (OITB-S),

by principally the anti-methoxyl group. Sulfonate esters

(II) and (III) appeared to be principally exhibiting the

electron-withdrawing properties of the methoxyl group with

possible small steric differences and "OITB" interaction

causing a slight rate acceleration for (II).














CHAPTER I
INTRODUCTION

The interaction through space of nonbonding pairs of

electrons on atoms such as oxygen, nitrogen, and sulfur,

with potentially unsaturated reaction centers, has been an

important area of investigation during the last quarter

century. Covalently bonded atoms with unshared electrons

can lower the energy of the transition state, and facili-

tate the formation of a carbonium ion by sharing such

electrons with the incipient positive center. This kind

of participation is most often manifested by an increase in

the rate of reaction by several orders of magnitude and

sometimes specific stereochemical results in the productss.

The anchimeric assistance provided by double bonds is

a second tyne of orbital interaction through space which

has received extensive study. Its extent and effectiveness

was most eloquently demonstrated by Winstein and his co-

workerslin their solvolyses of compounds such as (1), (2),

and (3). At 25C (2) solvolyzed 1011 times faster than (1)

and (3) solvolyzed 1014 times faster than (1). The cyclo-

propyl group also provides anchimeric assistance by orbital

interaction through space. For compound (4), cyclopropyl

participation results in an acetolysis rate which is 1014

times faster than that of (1).





I _












OTs OTs OTs OTs







1 2 3 4




More recently secondary through space olefin-olefin and

non-bonding pair-olefin orbital interactions, such as in

systems (5) and (6) respectively, and their effect on pri-

mary neighboring group interactions with potentially
3,4
unsaturated centers has assumed importance.3' Thus, al-

though both 5 and 6 solvolyzed faster than the 7-norbornenyl


X








X


5 6


system (2), there is still some question as to whether the

remote double bond in (5) and the nonbonded pairs on oxygen

in (6) are actually responsible for this rate accelera-
3,4
tion. This study was initiated to probe the extent and









effectiveness of such "two-orbital interactions through

space." It will he principally concerned with the inter-

action between the non-bonding orbital of a methoxyl group

and the 7-orbital of a double bond. Previous work in

these and related areas of through-space interactions are

briefly summarized in the following discussion.

The neighboring group reactivity of methoxyl groups

in solvolytic reactions has received extensive investigation

and documentation in the chemical literature.5 Winstein

and his coworkers5a have summarized their investigations of

primary MeO-3, 4, 5, 6, and 7 participation in acyclic

systems having the general structure (7). They found that



MeO-(C2) n-CH2OBs

7



primary MeO-5 and primary MeO-6 participation resulted in

substantial acceleration of solvolysis rates, while primary

MeO-3, 4, and 7 participation was less important. They

proposed that these reactions proceeded through cyclic

oxonium ions such as (9) and (14) which further reacted via

Me-O cleavage to yield tetrahydrofuran or tetrahydropyran

like products respectively, or by methylene-O cleavage to

yield retained solvent substituted or rearranged methoxy-

acetates such as (10), (11), (15), and (16).









SCHEME I

Me S
Me Me I I
I I -OBs + SOH -H+ OS OMe


10 11

8 9

MeOBs
\+ SOH and/or
MeOS


12

Me S
I I
Me Me + SOH OS OMe
+ OOBs C-- H
O15 16


13 14
+MeOBs
+ and/or
MeOS

17





MeO-3 participation by secondary and tertiary methoxyl

groups also occurs. Examples of participation of secondary

Br
H
H Me
MeOMe Me H

s Br M

H OMe

18 19 20









methoxyl groups are found in (18), (19), and (20), which

yield, in acetic acid, methoxvl-acetates of retained con-

figuration.5b'c Tertiary methoxyl anchimeric assistance in

(21) was reported to be approximately 1500 when aqueous


Me
MeO H Me + H OMe
I I Me>.H +
Me-C ---C-H Me C C C------ H
I I Me H Me
Me OBs H

21 22 23j






+
He Me
2 I OMe
MeOH + Me- --CHO --- Me -C-- C
I -H I \
-H H
H H

25 24




dioxane was the solvent.5d Isobutyraldehyde (25) was the

major product of hydrolysis.
5e, f
Noyce and coworkers5f conducted a most thorough

investigation of MeO-5 participation in the acetolysis of

trans-4-methoxycyclohexyl p-methanebenzenesulfonate (26)

in which they suggested that anchimeric assistance by the

methoxyl group first involves partial bonding to the reaction

center to give an internally solvated ion-pair intermediate

(27), which then collapses to the symmetrical ion (28).








SCHEME II


Me
Me
T S+ T S- t

?_--Nq s_ "--OTS_________
MeO OTs

26 27 28


T H

MeO e OAc \
0 OAc


OMe
20%

31


13.8%


10.2%

29


This symmetrical ion (28) then reacts with acetic acid to

yield trans-acetates (29) and (30), or undergoes elimination

to yield a 4-methoxycyclohexene (31).

Gassman and coworkers6 in their investigation of the

solvolytic behavior of 7,7-dimethoxybicyclo[2.2.1]hept-2-yl


MeO OMe



: OTs


MeO OMe





OTs








tosylates (32) and (33) found that although (33) solvolyzed

38 times slower than (32) at 250C, analysis of the products

indicated that there was methoxyl participation in (33) and

not in (32). It was proposed that (32) solvolyzed to ion


SCHEME III


MeO OMe MeO Me


HOAc

OTs OAc

95.5%
32 34


MeO OMe





4.5% OAc
35


MeO Me



Ts



33

MeO OMe



./-

39



MeO Me MeC




OTs
33


36





OAc --


29%
37


34 + 35


40 41









(39) and was attacked by the acetate ion via the two routes

indicated, with the exo-route being preferred for the usual

steric reasons. Compound (33) was thought to solvolyze via

a different route to first yield ion (40), which then opens

to oxo-carbonium ion (41). Attack by acetate ion then

yields compound (36). As the above schematic indicates, no

products from the solvolysis of (33), were found with the

ketal group preserved.

Oxygen and specifically methoxyl activation of double

bonds has recently been demonstrated in the cycloaddition

of electron deficient tetrazines to compounds such as (42) and





X Y X Y
Me Me Py


1 + N0 + N2

Me y Me Py

42 43 44



Py
X Y X Y


+ Py + N2


Py

45 43 46


b) X=Y=K c) X=Y=O


a) X=H, Y=OCH3








7,8
(45). Reaction of (42-a) with 3,6-di(2'-pyridyl)-s-

tetrazine (43) was approximately 30 times faster than the

unsubstituted compound (42-b). Reaction of (42-c) was found

to be 22 times slower than the unsubstituted compound.

Using a frontier molecular model, Paddon-Row has

explained these results in terms of orbital interactions

through space (OITS) operating between the substituents

and the double bond. 7 For a HOMO-LUMO (reagent) controlled

reaction, which is the case for the reactions of (42) and

(45) with s-tetrazines, anti-bonding admixture of a syn-

oxygen non-bonding orbital into the bonding 7-molecular

orbital of (42-a) or (45-a) raises the energy of this orbi-

tal, thus narrowing the IIOMO-LUMO energy gap with a resultant

rate enhancement. For the ketones (42-c) or (45-c), bonding

admixture of the n* molecular orbital of the carbonyl group

into the r-molecular orbital of the double bond lowers the

energy of the latter orbital and thus widens the HOMO-LUMO

energy gap leading to a rate retardation.

Studies have also been conducted by other groups of
9-12
workers in which oxygen apparently has been found to

activate the double bond to cycloaddition. Normally

norbornene (2)-X and its anti-7 substituted derivatives

react exclusively by exo-cycloaddition to give endo, exo

adducts such as (48)-X.









R4
P4
P X
R iR

/ + l-a 1

R1
2x 47 48

a) R=R1=H

b) R=R= Cl

c) R=C1, RI=OMe


Similar stereospecificity might have been anticipated

for norbornadiene and its 7-substituted derivatives (3a-e);

however, surprising significant amounts of cycloaddition

occur from the endo-face of both the syn- and anti-double

bonds (Table I). In fact, if an oxygen containing substit-

uent is located at the bridge position, e.q. 3b-d, endo-

addition outweighs exo-addition by a factor of 2.5-3.0:1.11

Furthermore, endo, syn-adduction appears to occur to at

least as great an extent as endo-anti-addition despite an

increase in non-bonded interactions between the 7-substituent

and the C-4a, C-8a hydrogens in the transition state for the

formation of adduct (49-c). The stereospecificity of these

reactions was thought to be reflected in the product distri-

bution of 7-methylnorbornadiene (3-e), in which it was found

to react "normally" to yield principally adduct (51-e).

This particular experimental result clearly requires some

alternate explanation for the enhanced endo mode of addition













3-X


3-X


Cl6



47-b
1 47-b


a) X=H
b) X=OAc
c) X=OCOPh
d) X=Ot-13u
e) X-Me


X







C16
6


Table I
Relative Yields of Adducts
Cpd 49 50 51

3a 4% 96%a
3b 47% 28% 25%a
3c 40% 35% 24%b
3d 58% 27% 15%
3e 4% 9% 87%b


a
Source
bSource


of values is reference 9
of values is reference 11


in adducts of (3b-d). As early as 1967,12 it was proposed that

the proximity of the electron-rich oxygen atom activates the

double bond towards electrophilic attack by essentially a

through-space interaction. The same type of frontier mole-

cular orbital model used by Paddon-Row,7'8 as previously









stated in this study, has been proposed to explain the

results. This model essentially proposes that anti-bonding

admixture of the syn-oxyven non-bonding orbital into the

bonding n-molecular orbital raises the energy of the latter

orbital, thus narrowing the IIOMO-LUMO energy gap with a

resultant rate enhancement.

Haywood-Farmer et al., 4 in their investigation of

neighboring cyclopropyl participation in pentacyclo-

[6.3.1.13'6.027.0911 ]tridec-13-yl brosylate (52)-OBs found

a rate acceleration of 104.6 relative to (53)-OBs, and no

product of retained structure (52)-OAc. The extensive


OBs Bs





52 53




rearrangements observed were thought to arise by initial

formation of the trishomocyclopropenium ion (54), which

could subsequently rearrange to ions such as (55), (56),

and (57), and following attack by acetate ion lead to six

of the observed acetate products.









SCHEME IV



Bs





52 54 55













+ +
56 57


Battiste and Timberlake15 then tried to modify the

structure of (52)-OBs to retard or prevent the extensive

rearrangements found in its solvolysis. They substituted

ketal and keto groups at the 12-position to give (58)-OBs

and (59)-OBs. It was felt that these electron-withdrawinq





X X


MeO

0









groups would retard rearrangements to ions having positive

charge Beta to the ketal or keto functionality and thereby

might provide some insight into the nature of the trishomo-

cyclopropenium ion derived from (52)-OBs.
16
Work reported by Gassman and coworkers on the

acetolysis of exo-bicyclo[2.2.1]heptan-7-on-2-yl tosylate

(60)-OTs and endo-bicyclo[2.2.1]heptan-7-on-2-yl tosylate

(61)-OTs tended to support their hypothesis. Exo-bicyclo

0 0 0






x +
60 61 62


[2.2.1]heptan-7-on-2-yl tosylate (60)-OTs not only did not

exhibit rate acceleration similar to other 2-norbornyl

systems, but actually solvolyzed six times slower than the

endo-epimer (61)-OTs.1617 This unusual behavior was attrib-

uted to the normal solvent-assisted ionization of (61)-OTs

and an absence of stabilization from the formation of

bridged ion (62) in the solvolysis, because it places a

partial positive charge next to the carbonyl group.

Timberlakel5 determined the acetolysis rates of

(58)-OBs and (59)-OBs, and also gave rate estimates of the

unsaturated brosylates (63)-OBs and (64)-OBs. Of particular

interest to the present study and most surprising was the












BMeO Me





MeO
MeO 69%
63-OBs 65


OBs





0C


+ MeO2C--


3. 3'%


64-OBs


observation that

rate or somewhat


(63)-OBs solvolyzed at nearly the same

faster than (68)-OBs and yielded 69% of


OBs






68



(65) as the major product. The absence of rate deceleration

in (63)-OBs and the methoxyl-transfer product were inter-

preted as indicating participation by the lone-pair of the

syn-methoxyl oxygen in the transition state by stabilization

of the developing, delocalized positive charge. The syn-


19%

66








methoxyl lone pair mixing with the i-bond was expected

to raise the energy of this orbital and therefore promote

better mixing with the developing p-orbital center in the

transition state.

At 50C (58)-OBs had an acetolysis rate of 3.42 x

10- s- and (52)-OBs one of 2.54 x 10-s-1. This slight

acceleration of the ketal substituted brosylate over the un-

substituted brosylate and the 57.7% of methoxyl-transfer

products was also interpreted as indicating participation

similar to that observed in (63)-OBs.

The present study was initiated to probe the basis of

these surprising results. Rate estimates only had been

obtained for (63)-OBs and (64)-OBs because of the poor

solubility of the p-bromobenzenesulfonate esters.

Timberlake's experimental procedures also indicated that

there were some problems with the solubility of some of

the other sulfonate esters that were solvolyzed. A very

important requirement of this study was the synthesis of

sulfonate esters which were soluble in the buffered acetic

acid used as the solvolytic medium.

It was thought that the synthesis of alcohols (63)-OH,

(64)-OH, (68)-OH, (69)-OH, (70)-OH, and (71)-OH, and their

subsequent conversion to soluble sulfonate esters would

provide some measure of the true extent and nature of

methoxyl participation. Specifically, (63)-OH would exhibit

the normal electron-withdrawing characteristics of a











OH H OH


MeO





MeO
03-011 6 4-01! 68-011



OOH


MeO H Me


H MeO H


69-OH 70-OH 71-OH



methoxyl group by deceleration of the rate when compared to

(68)-OH. The syn-methoxyl compound, (69)-OH, was expected

to be even faster than (63)-OH because the anti-methoxyl

group with its electron-withdrawing properties would now be

exchanged for a hydrogen. The keto compound (64)-OH was

expected to exhibit the normal electron-withdrawing proper-

ties of the carbonyl group and would be compared with the

inductive properties manifested by one and two methoxyl

groups in alcohols (69)-011, (70)-OH, and (63)-OH. Compound

(71)-OH was to be used to study the possible distance at

which methoxyl participation was still effective in causing

solvolytic rate acceleration.















CHAPTER II
SYNTHESTS AND CIIHMISTRY


The synthetic schemes employed for the preparation of

the precursors and compounds used in this study are pre-

sented in the flow diagrams in Schemes V, VI, VII, VIII,

and IX.

The preparation of 7-norbornadienyl benzoate (3)-OBz

was accomplished using Tanida'sl8 procedure plus a number

of modifications. Norbornadiene, benzoyl peroxide, and an

equal molar mixture of cuprous bromide and cuprous chloride

were refluxed in benzene for three days. After removal of

the solvent and distillation of the black residue, a 29%

yield of (3)-OBz was obtained. Phenyl magnesium bromide

reacted smoothly with (3)-OBz to yield after distillation

74.8% of 7-norbornadienol (3)-OH. Reduction of the double

bond syn to the oxygen of (3)-OH was accomplished using

lithium aluminum hydride in ether 19 to yield an 84% con-

version to anti-7-norbornenol (2)-OH. Conversion of (2)-OH

to the corresponding acetate was accomplished by using

acetic anhydride in refluxing pyridine20 to yield 87.6% of

anti-7-norbornenyl acetate (2)-OAc. Hexachlorocyclopenta-

diene and (2)-OAc were placed in a glass bomb and heated

to 1400C for 31-45 hours.21 After workup and recrystalli-








SCHEME V




Bz H

( tCO MgcBr

/ II ether
3 CuBr/CuC1 3-OBz 78% 3-OH
29% LiAl


v u 140C
72-OAc 64.5%

88.11 LiA1H4
ether
C16
H

^ 7Na,t-BuOH
THF

72-OH 71%



pyric


s





68-OTs


OAc 0 OH

Ac20
pyridine

2-OAc 87.6% 2-OH





OH





68-OH


BsC1
in pyridine



-OBs





68-OBs









zation from hexane (72)-OAc was obtained as white prisms,

m.p. 132-133C. Conversion of (72)-OAc to the corresponding

alcohol (72)-OH was accomplished by its addition to a

chilled solution of lithium aluminum hydride in anhydrous

ether. The reductive-dechlorination proceeded smoothly to

yield, after sublimation under reduced pressure (0.5 torr,

90-94C), a waxy white solid, (68)-OH. The tosylate and
22
brosylate of (68)-OH were prepared in the usual way2

using the corresponding sulfonyl chlorides and pyridine.

Hexachlorocyclopentadiene reacted exothermically with

methanolic potassium hydroxide to give 5,5-dimethoxy-

1,2,3,4-tetrachlorocyclopentadiene (47-c), a well known
23
reactive diene. The Diels-Alder cycloaddition of

(2)-OAc with ketal (47-c), yielded 12,12-dimethoxy-3,4,5,6-

tetrachloro-endo, exo, anti-tetracyclo[6.2.1.13'6.02'7]-

dodec-4-en-ll-yl acetate (73)-OAc. Conversion of (73)-OAc

to the corresponding alcohol (73)-OH was accomplished by

its addition to a chilled solution of lithium aluminum

hydride in anhydrous ether. Reductive-dechlorination

proceeded smoothly to yield, after recrystallization from

hexane,a fluffy white solid (63)-OH. Hydrolysis of (63)-OH

with 5% aqueous sulfuric acid yielded (64)-OH. The alco-

hols (63)-OH and (64)-OH were converted to their respective

tosylates using p-methylbenzenesulfonyl chloride and

pyridine.22 (Scheme VI).

The synthesis of alcohols (69)-OH and (70)-OH presented

a number of formidable synthetic problems. Attack of









SCHEME VI


Cl6 MeO

S KOII/MeOH
677.3 6 c-

47-c


2-OAc


2-OAc


44.8%


C14
4 w
OAc

LiAlH4 MeO

ether
MeO
73-OAc


OO
(64)-OH


TsC1
pyridine


5% H2 SO
ether


63-OH


TsC1
pyridine


(63)-OTs


73-OH


(64)-OTs









nucleophiles on ketones of the general structure (74) always

results in stereospecific attack of the nucleophile across



O
Nu:- Nu H1

I\.. a


(75)


the double bond to yield structures with the general struc-

ture (75). This stereospecific attack has been demonstrated
2Aa
for hydride attack24a and grignard reagents such as methyl-
24b
magnesium bromide and phenylmagnesium bromide.4b

Reduction of a suitably protected (64)-OH followed by


OX


1)- H
2) H120


64-X


OX
CH3 I


H

Mec


70-x


methylation would lead to a most satisfactory synthesis of

(70)-OH, but provide no prospect of obtaining (69)-OH in a
25
similar manner. Earlier work done by this author2 and

modelled upon studies done by Eliel and others provided

a solution to this synthetic problem.









Dichloroaluminum Hydride, generated from a 4:1 molar

mixture of aluminum chloride and lithium aluminum hydride

in anhydrous ether, yielded a highly stereoselective reduc-

tion of ketals with the general structure (77). Of direct

interest to this study was the large amount of syn-methoxyl


Me OMe MeO-C H


HAlC12
Et20
86%
77
78


H OMe


+ 7

14%

79


ether (78) provided by this reagent.25 Furthermore, the

relative percentages of the isomers could be reversed by

changing the reagent to a 2:1.5 molar mixture of aluminum

chloride and triethylsilane to yield predominantly the


MeO OMe H OMe


2 AlC13
/ L I
1.5 Et SiH
85%

77 79


MeO H


+ /

15%

78


anti-methoxyl ether (79). It was felt that these reagents

would provide the answer to our synthetic problems.

The precursor for the synthesis of (69)-OH and (70)-OH

was (63)-OH and presented some special problems because of









its high susceptibility to rearrangement under the proposed

experimental conditions. The aforementioned synthetic pro-

cedures made it necessary to protect the alcohol function-

ality from reaction with aluminum chloride and/or dichloro-

aluminum hydride, while the ketal portion of the molecule

was beinq reduced. It was felt that sterically hindered

silyl ethers were the best possible protecting groups for

such synthetic procedures. As summarized in Scheme VII,

tert-butyldiphenylchlorosilane27 was the first reagent used

to yield a sterically hindered silyl ether. The resulting

silyl ether was stable to the experimental conditions and

yielded on reaction with the dichloroaluminum hydride the

desired syn- and anti-methoxyl isomers. A major problem

arose when it was found that removal of the silyl group with

tetrabutylammonium fluoride27b could not be accomplished

without destroying the substrate (Scheme VII).

Our efforts were then shifted to silyl ethers that

had smaller substituents attached to silicon than the tert-

butyldiphenylchlorosilane. Silyl ethers were synthesized

using diisopropylmethylchlorosilane, tert-butyldimethyl-

chlorosilane, isopropyldimethylchlorosilane, triethylchloro-

silane, and trimethylchlorosilane. All of the silyl ethers

were stable to the reaction conditions employed and yielded

the desired isomer mixture. The triethylchlorosilane

derivative was finally chosen because of its stability to

aqueous conditions, the ease of separation of the silylated









SCHEME VII


Oil

,3e (Me)3CSiCl2Cl Me
MeO Imidazole, DMF
MeO or Et3N Me
63-OH






OSit2 C(Me) 3


H MeO

Me 15% i
70-OSi2C(Me)3


Bu4NF, THF, 25C

2 days


OSip2C(Me)3

0


63-OSiit2C(Me)


4:1
AlCl3/LiAlH4


OSi,; 2 C(Me) 3
i-- r 2 3- -


85%
69-OSi%2C(Me)3


no desilylation


Bu4NF, THF, 50C
12 hours


Bu4NF, glyme, 80C


Bu4NF, diglyme
1100C


no desilylation


no desilylation


black tar









SCHEME VIII





MO Et3SiCl/Imidazole MeO
McO / 7 /__ ----------- =
or
1.2:1.5
MeO MeO
63-011 Et3SiCl/Et3N


4:1
ACI 3/LiAlH

91.7%




63-OSiEt
3


2:1.5
A1C 3/Et SiH

91.8%


85%


MeO 70-OSiEt3

15%


iEt3 OSiEt3


MeO

H


70-OSiEt


69-OSiEt
3
or

70-OSiEt
2


Bu NF

THF, 25C
5 hrs


69-OSiEt
-3


69-OH or 70-OH


63-OSiEt













Cl6

1iOH/EtOH












Na EtO
t-BuOHI
THF EtO


\1i


1.2 Et SiCl

1.5 Et N


EtO 8-OH
82-OH


82-OSiEt
3

3Ai
1.5 Et SiH
3


83-OH + 84-OH


TBu4NF

THF, 250C


EtO


84-OSiEt3


83-OSiEt3


SCHEME IX


140C


EtO OEt









Cl4
8o




c14


-OAc





2-OAc


81-OAc


81-OH


OSiEt





28


isomers, and finally the mild conditions under which

desilylation could be accomplished (Scheme VIII).

The tosylates of (69)-OH and (70)-OH were prepared in
22
the usual way with tosyl chloride and pyridine.

Scheme IX, which is very similar to Scheme VIII,

indicates the synthetic steps used to synthesize (83)-OH

and (84)-OH. This reduction of the diethoxy ketal appears

to be even more stereospecific than that found for the

dimethoxy ketal.

The IHnmr spectra of all of the alcohols and some of

the sulfonate esters are included in the following figures.







29















0
o





-rl
1)



O3










O*
-x0






x




0
41 0
a)









-0








CC



4 0
r"l








a)
-o
EC


; )







30













0

-P

;I


--J

'o1
FII









00

0
o
'l0






(1)

0
ro


u 1)

'- C











w>'o









0-
^ -8^'^l N H
_____ ,- .-_-^ _.. -. _ ^ -'. w H
---------- ------ ^ -- ->e a

























































3 =


a--8 8-9 S ---


O
0








I




xo
0-1
>1







0
0,
-1
(l












0
c

















0l



I
- 0









00










m .


cl

0
H I
mr 1-1
i-l

























0
> *
U o





*H --i
S4-1





t l


0





>14
I -H

X(U

OS
N -* P






I
.-l




S 0'
aD
El
'-i

o On







H *

We
-H-l
0 *






















0I

0



4L)
4-)
Q)











01





I












H
4O4
a














. r-
0







t O






0
1-4
41
-r ( I
C)
r-4
C4








E-1


4-


















O
I


0






co

I
"O



0-1
N IO
r--!




0
1.41

EU
I N
N,-
r. a



W H



0C
,-
O >1








CN








C I
w; cza





































o
0





0
U

U

















I



0


01-
-I








0
4cI









o
Si0
0r-f


^-8-^-3-
























I





rE





0
o
IO
0 1
-1 -U
U-


0


-P,-U


I 0

C C
oiCa

-0




4)j
4 ,9


oYa



S CI
C


cH
o





U I









'C
0



,4 0
h T


1












































4rI


0

0

41


-I


S,

O
_C:
H










4-1



0)



4-o
N
D r
~CI
0








cl
a)-









-o
00

0'0
.0 o




SLO








38














o

0
>1

rCo

.4
Q)
-*




Co








CO
-r-I







0


>1

a

ea

O m
,J I











Ct)M








Si
U O
I-1-














mH
'-I




z Io
4-1















CHAPTER III
RESULTS AND DISCUSSION


Kinetic and Product Results


The acetolysis rates of the syn-methoxyl (69)-OTs and

anti-methoxyl (70)-OTs along with the ketal (63)-OTs, ketone

(64)-OTs and unsubstituted tosylate (68)-OTs were determined

titrimetrically and are listed in Table II.

The acetolysis products from tosylates (63)-OTs, (69)-

OTs, and (60)-OTs are compiled in Table III with their

appropriate distribution and the conditions under which they

were obtained.

The activation parameters AHt, ASt, and AG-, were

derived from the following equations and are listed in

Table IV for compounds (63)-OTs, (64)-OTs, (69)-OTs and
28
(70)-OTs. Great care should be exercised in the use and

firm acceptance of the enthalpy and entropy values of


TrT kT
T2 1 k2T1
AHt = 4.576 2 1 log k--

kT k
H 1 k
AS = + R(n -) -R(Rn )


AGt = 4.576 T (10.3188 log k + log T)










Table II

Rates of Acetolysis of Several Endo, Exo-Bismethanonaph-
thalene Tosylates


k(s-1)b


Substrate






68-OTs

OTs




MeO 70-OTs

OTs

MeO


H 69-OTs

OTs


MeO


MeO 63-OTs



64-OTs


64-OTs


-5
5.98 x 105





-5
2.60 x 105
-5
7.41 x 10





2.16 x 10-5
-5
6.91 x 10





-4
1.10 x 104
3.84 x 10-4
3.84 x 10


25. 0c






25.0c
35.0c




c
25.0
35.0





25.0 e
35.0




50.0e
60.0
25.0a


Extrapolated from


other temperatures


bAll rates were determined in acetic acid buffered with
0.02879 M NaOAc.
Average of two runs
d
One run only
Average of three runs


k 25
rel


1.






0.43






0.36







1.84


0.015


2.41
7.82
9.09










Table III


Identity and Relative Percentages of Products from Acetolvsis
of several Endo, Vxo-Bismethanonaph Lhalene Tosylates


Substrate


Products


10o
ITs MeO
11 5

MeO

2 7


AcO




O


MeO
63-OTs


Time
2.4 half-lives
5.7 half-lives
10.4 half-lives



OTs


MeO


69-OTs



10 half-lives


Relative Percentagesc
94% 6%
93.5% 6.5%
90% 10%


84-OAc


H 84-OTs


15%


OTs AcO -


H


MeO MeO


70-OTs


>10 half-lives


85-OAc


96%


TsO





MeO

85-OTs


4%


bOther unidentified products) also produced
All solvolyses done in acetic acid buffered with sodium acetate
Percentages determined by integration of IInresonances and
comparison with authentic spectra.
















0 0 a)


























ImI
N N ON (L














H,- 0



+1 +1 +1 +1


N o Lm m












































I I I
+1 +1 +1 +1






















I | Ir q
0)1 | o ~1 o|









Table V


Compound

63-OTs
64-OTs
68-OTs
69-OTs
70-OTs
7-norborny
tosylate
anti-7-
norborneny
tosylate
syn-7-
norborneny
tosylate
aExtrapola


Comparison of Solvolytic Rates at 250C

k(s-1) krel

1.10 x 10-4 1.73 x 1010
9.09 x 10-7 1.43 x 108
5.98 x 10-5 9.39 x 109
2.16 x 10-5 3.39 x 109
2.60 x 10-5 4.08 x 109


6.37 x 10 15a



9.04 x 10-4a


1



1.42 x 1011


2.60 x 10-11 4.08 x 103
from other temperatures


'1



'1



1

ted


Reference

This work








29



29,30



31


(69)-OTs and (70)-OTs because of a number of experimental re-

strictions and problems. Although the kinetic data for these

esters appear reasonable, as indicated by acceptable values

for the free energies of activation, they were determined on

a smaller amount of R-OTs and therefore would tend to be much

more sensitive to the inherent experimental errors. Further-

more, these rates were complicated by a significant amount of

ion-pair return and this is clearly reflected in the product

analyses and lower infinity titers (Chapter IV). For purposes

of comparison of the acetolysis rates of (64)-OTs at 50 and

600C to those of the other tosylates at 25C, the observed

rate constants of (64)-OTs were extrapolated to 250C (Tables

II and V) using the equation:2c


2.303 log k -2.303 log k=AHIt/R(- ) + 2.303 log T/T2
21 T2 o 2


----------









Discussion


The kinetic results obtained in this study do not

support the contention of significant lone-pair involvement

of the syn-methoxyl qroup in the rate-determining ioniza-

tion step of tosylates (63)-OTs and (69)-OTs. This is

clearly in contrast to the interpretation of the Diels Alder

cycloaddition discussed in Chapter I, despite the fact that

the same type of frontier orbital HOMO-LUMO approach would

seem to be applicable. Although the ketal substituted

tosylate (63)-OTs does exhibit a rate acceleration of 1.84

when compared to the unsubstituted tosylate (68)-OTs, this

is still a relatively small acceleration compared to the

major alteration of double bond reactivity noted in the

cycloaddition reactions. Such results cause one to question

whether the transition states of cycloadditions involving

electron-deficient dienes and solvolytic reactions with their

positively charged centers are really comparable. Such a

comparison is not fully addressed in this study, but it

appears from our results that there are major differences in

the transition states, which account for the lack of

frontier-orbital control (FMO). Although FMO type explana-

tions have been invoked to explain reactivity differences in

neighboring group assisted ionization processes, they are

probably better correlated with charge-control factors.32

A reexamination of the solvolysis products in this work

indicates that at 2.7 half-lives, 94% of the product is the

keto ether (65) which results from methoxyl transfer. The









remaining 6% of product is the acetate (66) (Table III).

At 5.4 half-lives the ratio of (65) and (66) are, within

experimental error, virtually unchanged. At greater than

10 half-lives, the ratio of (65) to (66) has changed

slightly and a new products) is observed, whose identity

has not been established. The major product (65) at greater

than 10 half-lives still remains and no trace of the ester

from ring cleavage (67) was observed, although it could

have been missed because of the limited sensitivity of the

detection technique ( Hnmr).

Tosylate (63)-OTs can possibly be visualized as reacting

via the route indicated in Scheme X. The p-methylbenzenesul-

fonate (63)-OTs could first react in the rate-determining

step to form the nonclassical homocyclopropenium ion-pair

(86). Ion-pair (86) is probably best characterized as the

structure (87) in which the lobes of the original R-bond

are perturbed such that the lobes near the initial positive

center are larger and those near the syn-methoxyl group are

much smaller. Such an orbital arrangement provides for an

excellent interaction between the orbitals of the r-bond and

the p-orbital of the initial positive center, but a very

poor interaction between the small backside lobes of the

perturbed R-orbitals and the nonbonding orbitals of the

syn-methoxyl group. This kind of orbital arrangement does

not preclude methoxyl participation in the transition state

at some point, but does indicate that the effect should











SCHEME X


OTs + OTs


---'W-
Me DS MeO


Me 86
63-OTs 86


Ac AcO

Me

0 workup Me


UT






87


__ MeO
MeO




HoAc


MeO-4
transfer


MeO HoAc MeO-
and/or

workup
SMe I


most likely be relatively small. Our results indicate a

rate acceleration of only 1.84. Methoxyl transfer is then

accomplished via a structure such as (89) in which the anti-

methoxyl group provides assistance. The oxo-carbonium ion

(90) is obtained and product (65) results from either attack

by acetic acid/acetate ion or aqueous workup of the reaction


__









mixture. Attack by acetic acid on (87) results in the

ketal-acetate (88) which is hydrolyzed to the ketone during

aqueous workup.

The syn-methoxyl tosylate (69)-OTs appears to be

exhibiting principally the inductive effect of the methoxyl

group when compared to the parent sulfonate ester (68)-OTs.

It can possibly be visualized as reacting via the route

indicated in Scheme XI. It first ionizes to form the


SCHEME XI



r + OTs + OTs


Me Me MeOH


H
H H
69-OTs 91 992



internal
return HoAc




TsO


MeO MeO

H

84-OTs 84-OAc



homocyclopropenium ion-pair (91). The ion-pair is most

likely better represented by the perturbed orbitals shown in

figure (92). Internal return of OTs and attack by acetic

acid/acetate ion yields the observed products (84)-OTs and


I









(84)-OAc respectively. Methoxyl transfer is evidently not

favored here because of the ring strain caused by MeO-4

participation and the lack of any assistance from an anti-

methoxyl group as in (63)-OTs.

The anti-methoxyl tosylate (70)-OTs is also exhibiting

principally the inductive effect of the methoxyl group when

compared to the parent sulfonate ester (68)-OTs. It solvo-

lyzed at a rate which is only 43% of that for the unsubsti-

tuted sulfonate ester (63)-OTs. Tosylate (70)-OTs is thought

to react via the same route as that shown for (69)-OTs in

Scheme XI.

The keto tosylate (64)-OTs appears to be exhibiting the

electron-withdrawing properties of the carbonyl group. A

direct comparison between the inductive abilities of the

carbonyl group and one or two methoxyl groups indicates that

the carbonyl is better. However, this result is clearly

complicated by the differences in hybridization of carbon at

C12 and the resulting structural alterations of the substrate.
33
Professor Battiste33 contends that there is some through

space interaction in the ground state of sulfonates (63)-OTs

and (69)-OTs. He cites as evidence for this contention the

Hnmr spectra indicating greater shielding of the syn-methoxyl

group and the downfield shift of the hydrogen at C11 when

compared to that of the unsubstituted parent. (Table I)

He also proposes that maybe some credence should be given to

the consideration that the ionization step in all of the









substrates studied here is not the rate-determining step of

the reaction, but it is some step or combination of steps

later in the reaction. lie further states that this is a

speculative explanation with little experimental support.

Once the transition state is reached, the interaction

is apparently not observed and this appears to be reflected

in the results obtained in this study. There simply was no

comparable large alteration of double bond reactivity as

noted in the cycloadditions discussed in Chapter I. The

non-classical ion-pairs with perturbed orbitals proposed in

this study offer one explanation for the lack of any

interaction in the transition state by the electrons on

the syn-methoxyl group. Furthermore, once this interaction

is initiated the n-bridge and the initial positive center

are probably pulled closer together, thereby increasing

the distance between the w-bridge and the syn-methoxyl

oxygen. This is another factor favoring poor interaction of

the syn-methoxyl oxygen and the small backside lobes of the

n-bond.


1Hnmr Results


In a further attempt to ascertain the exact nature of

the possible steric and electronic influences on the reactive

sites in the compounds used in this study, the 1Hnmr spectra

of the alcohols were examined in order to determine if there

are any essential differences in the electron density at C11.









Table V
Chemical Shifts of theHn1Proton of several endo, exo, anti-
tetracyclo[6.2.1.03'6.02 '71dodec-4-en-ll-ols

Substrate Chemical Shift (6)








OH
6i8-OH 4.71






64-OH 4.85





MeO 69-OH 4.96



H

70-OH 4.85

Me



MeO 63-OH 4.96

MeO
OH



EtO

S82-OH 4.98

83-OH 4.80









Table VI lists the shifts of H1 and a number of trends are

evident. The resonance of H11 in the unsubstituted alcohol

is further upfield than all of the other keto, ether and

ketal substituted alcohols. The anti-ethoxyl alcohol has

the next resonance downfield at 6 4.80. Surprisingly the

keto and anti-methoxyl alcohol have H11 resonances at the

same chemical shift. Because of the obvious difference in

electron-withdrawing properties of these two groups, one is

definitely forced to consider other factors beside inductive

effects in discussing these resonances. Steric factors must

be causing some major differences in the actual structure of

these compounds. The syn-methoxyl (69)-OH, dimethoxyl (63)-

OH, and diethoxyl (82)-OH, compounds have essentially the

same chemical shift for their H11 proton. This observation

is most difficult to explain considering the obvious induc-

tive differences between one and two ether groups.















CHAPTER IV
EXPERIMENTAL

Physical Measurements

General


Melting points were determined on a Thomas-Hoover

capillary melting point apparatus and are uncorrected.

Elemental analyses were performed by Atlantic Micro-

lab, Incorporated, Atlanta, Georgia.


Spectra


Infrared spectra were recorded on either a Perkin-

Elmer Model 137 B or Beckman IR-10 spectrophotometer.

Infrared absorptions are described as: w=weak, m=medium,

and s=strong.

Mass spectra were obtained on an Associated Electronic

Industries (AEI) Model MS-3D mass spectrometer at 70 eV.

Accurate mass determinations were obtained using the same

instrument linked with an auxiliary PDP-8 digital computer.

Nuclear magnetic resonance spectra were recorded on a

Varian Associates Model A-60, 60 MHz spectrophotometer, a

Varian Model XL-100, 100 MHz spectrophotometer, a JEOL

JNM-PMX60, 60 MHz spectrometer and JEOL JNM-FX-100 Fourier

Transform NMR Spectrometer. Chemical shift values for









1Hnmr spectra are reported in 6 units relative to tetra-

methylsilane (TMS) at 6 0.00. After the chemical shift

values are given in parentheses the multiplicity of the

peaks, the relative integration, the coupling constants

(J) where applicable, and the assignments of the peaks if

known. The symbols used for the multiplicities are s=sing-

let, d=doublet, t=triplet, q-quartet, p=pentet, and m=mul-

tiplet.



Synthesis

Preparation of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopenta-

1,3-diene (47)-c


A three liter three-necked flask was fitted with a

mechanical stirrer, pressure equalizing funnel, and a reflux

condenser. To this flask was added 486 grams (2.15 moles)

of hexachlorocyclopentadiene (Aldrich H 600-2) and 1000 mL

of methanol. To this mixture was added a solution contai-

ning 300 grams (5.35 moles) of potassium hydroxide in

100 mL of methanol at such a rate that a gentle reflux was

maintained. The mixture was stirred overnight at room tem-

perature and most of the methanol removed by distillation.

Methylene chloride was added to the mixture and filtered

to remove potassium chloride. The resulting 1500 mL solu-

tion was washed with 4 x 200 mL of water, dried with

anhydrous magnesium sulfate, filtered and the solvent

removed to yield a black oil. The black oil was distilled









(0.3-0.4 torr, 110-1230C) to yield 382 grams (67.3%) of

pale yellow oil. The 'Hnmr spectrum (CDC13) exhibited

only a singlet at 6 3.33. All other spectral data were in

agreement with those previously reported.23,34


Preparation of 7-norbornadienyl benzoate 3-OBz


The synthetic procedure of Tanid8 with some modifi-

cations was used to prepare this compound. In a typical

reaction 153 grams (1.66 moles) of norbornadicne, 2.4 grams

(0.0165 moles) of copper (I) bromide, and 1.63 grams

(0.0165 moles) of copper (I) chloride were placed in a

flask under a nitrogen atmosphere with 700 mL of anhydrous

benzene. This mixture was mechanically stirred and heated

to 400C. A mixture of 307.5 grams (1.27 moles) of benzoyl

peroxide (Aldrich 17,996-1) in 1000 mL of benzene was

slowly added over a period of 2 hours. After the addition

was completed the reaction mixture was gradually heated to

reflux and maintained for three days. The color of the

reaction mixture changes from an initial dark green, to

blue, and finally to orange. Note: The Benzoyl Peroxide

is not very soluble in benzene and this presents problems

during its addition. It can be added to the reaction mix-

ture all at once before heating but 6 hours or more must be

used to gradually raise the mixture to reflux temperature.

Failure to do so will most likely result in an explosion!

After cooling to room temperature, the solution was placed









in a large separatory funnel and washed successively with

2 x 150 mL of 5% ferrous sulfate, 2 x 100 mL of 3N hydro-

chloric acid, 3 x 200 mL of 10% aqueous sodium carbonate,

and 3 x 200 mL of brine. It was dried over anhydrous

magnesium sulfate, filtered and the solvent removed by

vacuum distillation to leave a black oil. The oil was

distilled (0.8-1.2 torr, 140-1500C) to yield 110 grams of

light brown solid. After washing with pentane, 102 grams

(29%) of white crystalline solid was obtained. The 1Hnmr

spectrum (CC14) exhibited the following resonances: 6 7.8-

8.1 (m, 2; ortho-aromatic protons); 7.1-7.5 (m, 3; meta-

and para-aromatic protons); 6.71 (t, 2; J=2,3 Hz; H2 and H );

6.59 (broad t, 2; J=2.0 Hz; H5 and H6); 4.77 (broad, s, 1;

H7; and 3.70 (sextet, 2; J=2.0 Hz; H1 and H4).


Preparation of 7-norbornadienol (3)-OH


A three-necked 2000 mL flask was equipped with a

reflux condenser, a pressure equalizing funnel, and provisions

made for maintenance of a nitrogen atmosphere over the

reaction. In this reaction a solution of 42 grams (0.198

moles) of 7-norbornadienyl benzoate (61)-OBz in 350 mL of

anhydrous ether was added to phenylmagnesium bromide, pre-

pared from 124.4 grams (0.792 moles) of bromobenzene and

19.2 grams (0.80 moles) of magnesium turnings in anhydrous

ether, at such a rate as to maintain reflux.18 After the

addition was completed, the mixture was stirred at room








temperature overnight. The flask was chilled and 350 mL of

saturated aqueous ammonium chloride solution cautiously

added to the chilled mixture. The aqueous and ether phases

were separated and the aqueous phase washed with 2 x 100 mL

of ether. All ether phases were combined and washed with

2 x 100 mL portions of saturated aqueous sodium chloride

solution and then dried over anhydrous magnesium sulfate.

After filtration and removal of most of the ether by rotary

evaporation, pentane was added to precipitate triphenyl-

carbinol. After filtration and removal of the pentane by

rotary evaporation, the resulting red oily mixture was

distilled (35-40 torr, 80-1100C) to yield 16 grams (74.8%)

of water white liquid. The 1Hnmr spectrum (CC14) contained

the following resonances: 6 6.50 (5,4; J=2.0 Hz; H2, Hi3

H5, and H6); 3.76 (broad s, 1; H.7); 3.38 (sextet, 2;

J=2.0 Hz; H1 and H 4); and 3.2 (s, 1; OH).


Preparation of anti-7-norbornenol (2 )-OH


A solution of 35 grams (0.323 moles) of 7-norbornadienol

(61)-OH in 250 mL of anhydrous ether was added to 24.5 grams

(0.646 moles) of Lithium Aluminum Hydride in 450 ml of

anhydrous ether under a nitrogen atmosphere at 0OC.19 This

mixture was heated to reflux for one hour, cooled in an

ice-bath, and 150 mL of water cautiously added. The solid

aluminum salts were dissolved on cautious addition of 350 mL

of 10% aqueous sulfuric acid and the resulting aqueous and

ether phases separated. The ether phase was dried over








anhydrous potassium carbonate, filtered, and the solvent

removed under reduced pressure to yield 30 grams (84%) of

slushy white solid. The 1Hnmr spectrum (CC14) contained
the following resonances: 6 5.98 (t, 2; J32.0 Hz; 1H2 and

H3); 3.57 (broad s, 2; II7); 2.53 (sextet J=2.0 Hz; H1 and

14); 2.21 (s, 1; Oil); 1.8 (m, 2; 5 exo and H6 exo); and

1.0 (m, 2; H5 endo and H6 endo).
5 endo 6 endo

Preparation of anti-7-norbornenyl acetate (2 )-OAc


Acetic anhydride (31 mL) was added to 30 grams (0.27

moles) of 7-norbornenol (62)-OHI dissolved in 31 mL of dry

pyridine.20 This solution was heated to reflux for one

hour, cooled to 25C and 50 mL of water added. The mixture

was stirred for 10 minutes, poured into 100 mL of water and

extracted with 3 x 100 mL of ether. The combined ether

phases were washed with 3 x 50 mL of 5% aqueous hydrochloric

acid, 100 mL of 10% aqueous sodium carbonate and dried over

anhydrous sodium sulfate. After filtration, the solvent

was removed by rotary evaporation to yield 36 grams (87.6%)

of pale yellow oil. This was generally used without further

purification as the 1Hnmr spectrum was identical to that

reported. However, the product could be distilled (35-37C,

3.5 torr) to yield a colorless oil. The 1Hnmr spectrum

(CC14) contained the following resonances: 6 6.02 (t, 2;

J=2.0 Hz; H2 and H3); 4.33 (broad s, 1; H17); 2.76 (sextet,

2; J=2.0 Hz; H1 and J4); 1.98 (s, 3; 02CCH3); 1.8 (m, 2;

H5 exo and H6 exo); and 1.0 (m, 2; H5 endo and H6 endo)









Preparation of 3,4,5,6,12,12-hexachloro-endo, exo, anti-

tetracyclo[6.2.1.13'6.02'7]dodec-4-en-ll-yl acetate (72)-OAc


In a typical reaction, 10.0 grams (0.066 moles) of anti-

7-norbornenyl acetate (2 )-OAc and 71 grams (0.262 moles) of

hexachlorocyclopentadiene were placed in a glass tube with

30 ml of carbon tetrachloride, frozen in a dry ice/isopro-

panol bath, pumped to 0.5 torr, sealed and heated to 1400C

for 31-45 hours.21 This resulting black mixture was cooled

to room temperature, opened, and the carbon tetrachloride

removed by rotary evaporation. The resulting black residue

was treated with activated charcoal in hexane. Final re-

crystallization from hexane yielded white prisms, m.p.

132-1330C. Overall yield after repeated washings of the

black residue with hot hexane and subsequent recrystalliza-

tion was 18 grams (64.5%). The 1Hnmr spectrum (CC14)

contained the following resonances: 6 4.80 (broad 2, 1;

H 11); 2.72 (s, 2; H2 and H7); 2.50 (q, 2; J=2.0 Hz; H1 and

Hg); 1.96 (s, 3; O2CCH3); 2.0 (m, 2; H9 exo and HI exo)

and 1.2 (m, 2; H9 endo and H0 endo).


Preparation of 3,4,5,6,12,12-hexachloro-endo, exo, anti-

tetracyclo[6.2.1.13'6.02'7]dodec-4-en-.l-ol (72)-OH


In a typical reaction, 18 grams (.0424 moles) of (63)-

OAc was added slowly under a nitrogen atmosphere to 4.0

grams (.106 moles) of lithium aluminum hydride in 200 mL of

ether cooled in an ice-water bath. This mixture was stirred









for one hour at room temperature, placed in an ice bath and

100 mL of water cautiously added. The mixture was allowed

to rise to room temperature and 200 mL of 10% aqueous

sulfuric acid was added and the mixture stirred until all

solids dissolved. The aqueous and ether phases were sepa-

rated and the aqueous phase extracted with 2 x 50 mL of

ethyl ether. All ether fractions were combined and dried

over anhydrous magnesium sulfate, filtered and the ether

removed under reduced pressure to yield 14.3 grams (88.1%)

of product, m.p. 131-132C. The 1IInmr spectrum (CDC1 3)

contained the following resonances: 6 4.08 (broad s, 1;

H11); 2.73 (s, 2; H2 and H7); 2.1-2.4 (m, 4; HI, HS,

19 exo' and I10 ex ); 1.69 (s, 2; OH) and 1.0-1.3 (m, 2;

H9 endo and H10 endo).

Preparation of endo, exo, anti-tetracyclo[6.2.1.13'6.02'7]-

dodec-4-en-ll-ol (68)-OH


In a typical reaction 60 grams (0.88 moles) of tert-

butanol was added to 40 grams (1.7 gram-atoms) of finely

chopped metallic sodium in 400 mL of tetrahydrofuran at

room temperature under a nitrogen atmosphere.35 To this

mixture was added 20.0 grams (0.052 moles) of (72)-OH

dissolved in 250 mL of tetrahydrofuran. This mixture was

mechanically stirred and maintained at reflux for 36 hours,

cooled to room temperature, and the excess sodium removed

by filtration through a wire screen. Water (500 mL) was









added to the filtrate to dissolve any sodium salts. This

was extracted with 2 x 100 mL of ether. The ether phases

were combined and dried over anhydrous magnesium sulfate,

filtered, and the ether removed by rotary evaporation to

yield 12 grams of mushy brown solid. The mushy brown solid

was sublimed (0.5 torr, 90-94C) to yield 6.5 grams (71%)

of slightly oily white solid, m.p. 110-112C (lit. 107-

1090C, 108-1090C) 21,35 The 1Hnmr spectrum (CC14) contained

the following resonances: 6 6.06 (t, 2; J=2.0 Hz; H4 and

H ) ; 4.71 (broad s, 1; H11); 2.85 (sextet, 20, J=2.0 Hz;

H1 and H8); 2.01 (t, 2; J=2.0 Hz; H2 and H7); 1.7-1.9 (m,

2); 0.8-1.4 (m, 4); and 1.26 (s, 1; OH).


Preparation of endo, exo, anti-tetracyclo[6.2.1.13'6 02,7]

dodec-4,en-ll-yl p-methylbenzenesulfonate (68)-OTs


A solution of 2 grams (0.0113 moles) of the alcohol

(68)-OH dissolved in 5 mL of dry pyridine was placed in an
22
ice bath. To this solution was added 4.30 grams (0.0226

moles) of freshly recrystallized p-methylbenzenesulfonyl
22b
chloride. The resulting solution was kept at 100C for

48 hours. The mixture was poured into 75 mL of ice/water,

stirred for 15 minutes, filtered, and washed with 100 mL

of ice water. After drying overnight under vacuum, the

crude ester was dissolved in benzene, treated with acti-

vated charcoal, filtered and recrystallized from a Hexane/

Benzene solution to yield 3.30 grams (88.5%) of white









needles, m.p. 102-1040C (lit. 102.5-1030C). The Hnmr

spectrum (CDC1 ) consisted of the following resonances:

6 7.20 (d, 2; aromatic protons); 7.32 (d, 2; aromatic pro-

tons); 6.06 (t, 2; J=2 Hz; H4 and H5); 5.42 (broad s, 1;

H1i1); 2.68 (sextet, 2; J=2 lHz; 11 and H8) ; 2.5 (s, 3;

aromatic -CH3); 2.05 (m, 4); 1.7-2.2 (m, 2); I9 exo and

H10 exo 1.0-1.5 (m, 2); H9 endo and H10 endo
10 exo 9 endo 10 endo
Anal.: Calcd. for C19H22SO3: C, 69.07; H, 6.71;

S, 9.68.

Found: C, 69.11; H, 6.75; S, 9.68


Preparation of endo, exo, anti-tetracyclo[6.2.1.1 .0 0]-
dodec-4-en-ll-yl p-bromobenzenesulfonate (68)-OBs


A solution of 1 gram (5.674 mmoles) of alcohol (57)-OH

dissolved in 3.5 mL of dry pyridine was placed in an ice

bath.22 To this solution was added 2.90 grams (0.01135 moles)

of p-bromobenzenesulfonyl chloride followed immediately by

10 ml of chilled dry pyridine. This solution was maintained

at 0.50C for 24 hours and then poured into 100 ml of ice/

water, stirred for 15 minutes, filtered, and washed with

100 mL of ice water. The crude ester was dried under vacuum

for 4 hours (0.1 torr, 230C). It was then dissolved in

benzene, treated with activated charcoal, filtered and the

solvent removed under reduced pressure. Recrystallization

from a benzene/hexane solution yeilds 2.02 grams (90%) of

white needles, m.p. 96-980C (d), (lit. 96-970C).36 The









1Hnmr spectrum (CDC1,) contained the following resonances:

6 7.68 (s, 4; aromatic protons); 6.05 (t, 2; J=2.0 Hz; H4

and H5); 5.48 (broad s, 1; H11); 2.87 (m, 2); 2.07 (m, 4);

1.6-2.0 (m, 2); and 0.9-1.54 (m, 4).


Preparation of 12,12-dimethoxy-3,4,5,6-tetrachloro-endo, exo,

anti-tetracyclo[6.2.1.13'6.02'7]dodec-4-en-ll-yl acetate

(73)-OAc


In a typical reaction, anti-7-norbornenyl acetate (2)-

OAc 9 grams (0.059 moles), was mixed with 18 grams (0.068

moles) of 5,5-dimethoxy-l,2,3,4-tetrachlorocyclopentadiene

(47) and 5 mL of carbon tetrachloride in a glass bomb. The

bomb was placed in a dry ice/isopropanol bath (-780C) and

the contents frozen. The contents were then pumped down to

0.5 torr while frozen and the mixture allowed to warm to

room temperature. This freezing and pumping procedure was

repeated two more times and then the bomb was sealed under

vacuum. The mixture was placed in an oil bath and heated

for 31 hours at 140C. The carbon tetrachloride was removed

to leave a black tar. Activated charcoal and 100 mL of hot

methanol were added and the hot mixture filtered through a

celite pad. White crystals slowly crystallized in the

methanol solution. Filtration yielded 11 grams (44.8%) of

white crystalline solid, m.p. 137-1390C (lit. 140-140.50C).15

The 1Hnmr spectrum (CDC1 ) exhibited the following resonances:









6 4.85 (broad s, 1; HI 1) ; 3.6 (s, 3; -OCH3); 3.55 (s, 3;

-OCH3); 2.60 (s, 2; H2 and H7); 2.45 (m, 2; J=2.0 Hz; H1

and H8); 2.0 (s, 3; O2CCII3); 1.95 (m, 2; 9 exo and H0 exo);

and 1.2 (m, 2; H9 endo and H10 endo).


Preparation of 12,12-dimethoxy-3,4,5,6-tetrachloro-endo,

exo, anti-tetracyclo[6.2.1.13'6.02'7]dodec-4-en-ll-ol (73)-OH


A three necked round bottom flask was fitted with a

reflux condenser, magnetic stirrer, nitrogen inlet, and

placed in a dry ice/isopropanol bath. Into this flask was

placed 2.47 grams (0.065 moles) of lithium aluminum hydride

and 125 mL of anhydrous ether. A solution of the acetate,

11.0 grams (0.026 moles) in 125 mL of anhydrous ether, was

added to the stirred mixture over a one-half hour period.

Stirring was continued for two hours after the addition was

completed. Water (2.5 mL) was added and the mixture slowly

warmed to room temperature. Aqueous sodium hydroxide, 15%,

(2.5 mL) was added followed by 7.5 mL of water and the mix-

ture stirred until a white solid formed. The solid was

removed by filtration and the ether dried with anhydrous

potassium carbonate. The solvent was removed by rotary

evaporation and yeilded a white solid, m.p. 120-1250C.

Recrystallization from 60-110"C petroleum ether or hexane

yielded 8.6 grams (88.4%) of white crystals, m.p. 131-1320C.

The 1Hnmr spectrum (CDC13) contained the following resonances:









6 4.06 (broad s, 1; H11); 3.57 (s, 3; OCH3); 3.50 (s, 3;

OCH3); 2.55 (s, 2; H2 and H17; 1.9-2.3 (m, 4; H1, H8, H9 exo

and H10 exo); 1.5 (s, 1; OH); and 1.2 (m, 2; H9 endo and

H10 endo)


Preparation of 12,12-dimethoxy-endo, exo, anti-tetracyclo-

[6.2.1.13'6.02'7]dodec-4-en-ll-ol (63)-OH


Gassman's procedure of reductive-dechlorination with

some modifications was used in this synthesis.34'35 A two

liter three-necked flask was equipped with a true-bore

stirrer, a pressure equalizing funnel, and a condenser fitted

with a nitrogen inlet. To this flask was added 450 mL of

tetrahydrofuran, 27 grams (1.16 gram-atoms) of finely

chopped metallic sodium, and 43 grams (0.58 moles) of tert-

butyl alcohol. This mixture was stirred and heated to

reflux and 11 grams (0.029 moles) of (65)-OH dissolved in

350 mL of THF added dropwise over a 1.5 hour period. The

mixture was stirred under reflux for 12 hours after the

addition was completed, cooled to room temperature and the

metallic sodium removed by filtration through a wire screen.

Water (350 mL) was added to the filtrate to dissolve the

sodium salts. The aqueous and ether phases were separated

and the aqueous phase extracted with 2 x 100 mL portions of

ether. The combined ether phases were dried over anhydrous

magnesium sulfate and the ether removed under reduced

pressure to yield 6.2 grams of light brown solid. Recrys-

tallization from hexane yielded 4.0 grams of fluffy white









solid, m.p. 114-1160C, (lit. 118-119oC).15 The 1Hnmr spec-

trum (CDC13) contained the following resonances: 6 6.15 (t,

2; J=2.3 Hz, II4 and 115); 4.96 (broad s, 1; 11 ) ; 3.17 (s, 3;

OCII3); 3.08 (s, 3; OCH3) ; 2.87 (p, 2; J=2.0 Ilz; 113 and H16);

2.23 (t, 2; J=2 Hz; H12 and H7); 1.8-2.0 (m, 4; II1, IIg,

H9 exo and 10 exo); 1.4 (s, 1; H01); and 1.0-1.3 (m, 2;

119 and H, ).
9 endo and H10 exo)

Preparation of 12,12-dimethoxy-endo, exo, anti-tetracyclo-

[6.2.1.13'6.02'7]dodec-4-en-ll-yl triethylsilyl ether (63)-

OSiEt3


Method A. This synthesis was accomplished using pro-
27b
cedures similar to those developed by Corey and other

authors.27b In a typical reaction triethylchlorosilane,

1.53 grams (0.010 moles), was added to a 25 mL round bottom

flask that contained 1.266 grams (0.186 moles) of imidazole,

2.0 grams of (52)-OH and 3.0 mL of dimethyl formamide. The

flask is stoppered and the mixture shaken until everything

dissolves. The mixture is stirred magnetically for one

additional hour and the flask placed in an ice bath. Aque-

ous 10% sodium bicarbonate, 10 mL was added to the chilled

flask and the whole mixture placed in a separatory funnel

after 15 minutes. An additional 10 mL of 10% aqueous sodium

bicarbonate was added to the mixture. The resulting mixture

was extracted with 4 x 20 mL of ether and the combined ex-

tracts dried over anhydrous sodium sulfate. Filtration and







removal of the solvent yielded 2.91 grams (98%) of pale

green oil. This material was used without further purifi-

cation but sometimes resulted in partial hydrolysis of the

ketal functionality to the ketone and is the reason an

alternate method of synthesis was developed.

Method B. In a typical reaction I gram (4.232 mmoles)

of (63)-OH was added to a 25 mL round bottom flask and

enough dimethyl formamide, (3.5 mL), added to dissolve

everything. Triethyl amine, 0.642 grams (6.348 mmoles),

was added and the flask placed in an ice bath. Triethyl-

chlorosilane, 0.765 grams (5.08 mmoles) was added and caused

formation of a thick paste. An additional 3 mL of dimethyl

formamide was added to make mixing easier and the mixture

shaken for 20 minutes at room temperature. The paste was

washed with 3 x 20 mL of anhydrous ether and these washings

passed through a short column of neutral alumina to remove

the last remnants of dimethyl formamide. The solution was

then dried over anhydrous sodium sulfate and the solvent

removed by rotary evaporation to yield 1.36 grams (91.7%)

of pale green oil. The 1Hnmr spectrum (CDC13) contained

the following resonances: 6 6.19 (t, 2; H4 and H5); 4.94

(broad s, 1, H11); 3.19 (s, 3; OCH3); 3.10 (s, 3; OCH3);

1.87 (broad s, 2; H2 and H7); 1.70-2.12 (m, 2; H9 exo and

H10 exo); 0.80-1.50 (m, 2; H9 endo and 10 end); 0.40-1.50

(m, 15; silyl ethyls).









Reaction of 12,12-dimethoxy-endo, exo, anti-tetracyclo-

[6.2.1.13,6.02'7 dodec-4-en-ll-yl triethylsilyl ether

(63)-OSiEt, with a 4:1 Molar Ratio of Aluminum Chloride/

Lithium Aluminum Hydride


This reduction was modeled after the reaction procedure

developed by Eliel and others.26a,37 A three-necked 500 mL

round bottom flask was equipped with a condenser and a

nitrogen inlet. This flask was immersed in an ice bath

and in a typical reaction 4.35 grams (0.0326 moles) of an-

hydrous aluminum chloride and 0.310 grams (8.160 mmoles) of

lithium aluminum hydride were added under a nitrogen flask

and immediately covered by 150 mL of anhydrous ether.

This mixture was stirred for 20 minutes at ice temperature.

The silylated ketal, 2.86 grams (8.160 mmoles) was dissolved

in 50 mL of anhydrous ether and slowly added to the ice-

cooled mixture. The mixture was stirred for 2 hours at

0-50C and an additional 10 hours at room temperature. The

faint red color characteristic of the oxo-carbonium ion was

produced almost immediately and remained for almost two

hours. The flask was chilled and 50 mL of water cautiously

added followed immediately by 50 mL of saturated aqueous

ammonium chloride. The aqueous and ether phases were

separated and the aqueous phase extracted with 2 x 25 mL of

ether. The combined ether phases were dried over anhydrous

magnesium sulfate and the solvent removed under reduced

pressure at room temperature to yield 2.31 grams (91.7%) of








pale green oil. FInmr spectroscopy reveals that two

products are present. The recovered product contained

approximately 85% of the syn-methoxyl isomer and 15% of

the anti-methoxyl isomer. This conclusion was based on

integration of the appropriate methoxyl absorptions and

also supported by earlier work.25 The isomer mixture was

subjected to column chromatography on freshly dried Silica

Gel or Silicar CC-7 using a 50/50 Hexane/Ether solvent

mixture. Separation is accomplished with some partial

desilylation during the chromatography.

Desilylation was accomplished by treating the silyl

ethers with tetrabutylammonium fluoride in anydrous tetra-
38-40
hydrofuran at 25C for 5 hours. Isolation of the pure

alcohols was accomplished by chromatography on Silica Gel

or Silicar CC-7 with an Ether/Hexane solvent mixture. The

major product was syn-12-methoxyl-endo, exo- anti-tetracyclo-

[6.2.1.13,6. 02'7]dodec-4-en-ll-ol (69)-OH, m.p. 95-970C.

Its 1Hnmr spectrum (CDC13) exhibited the following reso-

nances: 6 6.12 (m, 4; H4 and H5); 4.96 (broad s, 1; H 1);

3.40 (m, 1; H12); 13.18 (s, 3; OCH3); 3.00 (m, 2; H and

H6); 2.00 (m, 2; H2 and H7); 1.70-2.40 (m, 2; H1, H8,

H9 exo and H10 exo); 0.90-1.30 (m, 2; H9 endo and H0 endo

and 1.40 (s, 1; OH1). The infrared spectrum (KBr) contained

the following absorption bands: 3050 (s), 2850 (s), 1765 (m),
-i
1055 (s), 1035 (s), 1020 (m), 855 (m), and 760 (s) cm 1

The mass spectrum (70 eV) had m/e 206 (M+, 4.6%), 174 (11.8%),









146 (21.5%), 117 (60.1%), 105 (39.2%), 96 (20.1%), 92 (23.0%),

and 91 (100%).

Anal.: Calcd. for C H 102: C, 75.69; II, 8.79

Found: C, 75.43; H, 8.84

The minor product was anti-12-methoxyl-endo, exo, anti-

tetracyclo[6.2.1.13'6.02'7]dodec-4-en-ll-ol, (70)-OII, m.p.

102-1040C. Its 1Hnmr spectrum (CDC13) exhibited the fol-

lowing resonances: 6 6.07 (t, 2; H4 and H5); 4.85 (broad s,

1; H 1); 3.23 (s, 3; OCH3); 2.99 (m, 1; H12); 2.80 (m, 2;

H3 and H ); 2.15 (m, 2; H1 and H ); 2.00 (m, 3; H2, H7 and

OH); 1.68-2.34 (m, 2; 9 exo and H0 exo) and 0.90-1.60

(m, 2; H9 endo and H10 endo). The infrared spectrum (KBr)

contained the following absorption bonds: 3050 (s), 2800 (s),
-i
1330 (w), 1245 (m), 1100 (s), 1080 (s), and 745 (s) cm 1

The mass spectrum (70 eV) had m/e 206 (M+, 2.2%), 146 (24.8%),

96 (21.9%), 91 (100%), 92 (21.3%), 84 (28.6%) and 77 (24.2%).

Anal.: Calcd. for C13H 1802 C, 75.69; H, 8.79

Found: C, 75.55; H, 8.78


Reduction of 12-12-dimethoxy-endo, exo, anti-tetracyclo-

[6.2.1.13'6.02'7]dodec-4-en-ll-yl triethylsilyl ether

(63)-OSiEt3 with a 2:1.5 Molar Ratio of Aluminum Chloride/

Triethylsilane


A three-necked 250 mL round bottom flask was equipped

with a pressure equalizing funnel, and a reflux condenser

with a nitrogen inlet. The flask was immersed in an ice

bath and 1.467 grams (0.0110 moles) of anhydrous aluminum








chloride was added and immediately covered by 50 mL of

anhydrous ether. Triethylsilane, 0.961 grams (8.261 mmoles),

was dissolved in 35 mL of anhydrous ether and added to the

flask. The combined mixture was stirred for 15 minutes at

ice temperature. Addition of the silated ketal 1.93 grams

(5.507 mmoles), dissolved in 35 mL of ether immediately

results in a pale red solution. The solution was stirred

at room temperature for 7 hours after the addition was com-

pleted. The flask was chilled and 50 mL of saturated aqueous

ammonium chloride added followed by 50 mL of water. A milky

white ether phase results and dissipates on stirring to

give a clear solution. The aqueous and ether phases were

separated and the aqueous phase extracted with 2 x 20 mL of

ether. All ether phases were combined and washed with 20

mL of saturated aqueous sodium bicarbonate solution and

then dried over 50/50 anhydrous potassium carbonate/magne-

sium sulfate. After filtration and removal of solvent by

rotary evaporation, 1.62 grams (91.8%) of brown oil. 1Hnmr

spectroscopy reveals that two products are present. The

oil contained approximately 85% of the anti-methoxyl isomer

and 15% of the syn-methoxyl isomer. This conclusion was

based on integration of the appropriate methoxyl absorptions
25
and also supported by earlier work. The isomer mixture

was subjected to column chromatography on freshly dried

Silica Gel or Silicar CC-7 using a 50/50 Hexane/Ether

solvent mixture. Separation is accomplished with some








partial desilylation during the chromatography. The

physical constants of the syn-methoxyl and anti-methoxyl

are the same as those listed under the reduction done with

a 4:1 Molar Ratio of Aluminum Chloride/Lithium Aluminum

Hydride.


Preparation of tetrabutylammonium fluoride


A 40% aqueous n-tetrabutylammonium hydroxide solution

(45 grams) was neutralized with a 48% hydrofluoric acid

solution in a plastic container.27b38 The resulting mixture

was transferred to a 250 mL round bottom flask and distilled

under water aspirator pressure until a glassy solid just
39
begins to appear. A benzene-acetonitrile (1:1) mixture

was added 4 times in 5 mL portions and the resulting mixture

azeotropically distilled. The residue was then further

dried under vacuum (0.5 torr, 25C) for two days. A light

brown oil with a small number of crystals on the side of the

flask was eventually obtained. The light brown color dif-

fers from the water white oil obtained by a different
40
synthetic method and was not further purified as it per-

formed quite well in the desilylation procedure.


Preparation of 12,12-dimethoxy-endo, exo, anti-tetracyclo-

[6.2.1.1 36.0 ]dodec 4-en-ll-yl-p-methylbenzenesulfonate

(63)-OTs


In a typical reaction the alcohol (63)-OH, 0.500 grams

(2.116 mmoles), was dissolved in the minimum amount of dry









pyridine (77 drops) and the mixture placed in an ice bath.

Freshly recrystallized p-methylbenzenesulfonyl chloride,

0.806 grams (4.23 mmoles) was slowly added to the chilled

flask followed by 63 drops of dry pyridine to completely

dissolve everything. The flask was tightly stoppered and

kept at 10C for 2 days. The mixture was then poured into

100 mL of ice and water, stirred for 10 minutes and filtered

to yield a beige solid. The solid was washed with 25 mL of

cold water and then dried under vacuum (0.1 torr) for 4-8

hours. The beige solid was dissolved in either benzene or

anhydrous ethyl ether and treated with activated charcoal.

After filtration through a celite pad and removal of the

solvent under reduced pressure the product was recrystallized

from hexane to yield white needles. These needles were

dried for 8 hours at room temperature under vacuum (0.1 torr)

to yield 0.800 grams (96.8%) of product, m.p. 92-950C (d).

The Hnmr spectrum (CDC13) exhibited the following resonances:

6 7.75 (d, 2; aromatic protons); 7.31 (d, 2; aromatic protons);

6.08 (t, 2; H4 and H5); 5.53 (broad s, 1; H111); 3.14 (s, 3;

OCH3); 3.07 (s, 3; OCH3); 2.84 (m, 2; H3 and 116); 2.49

(s, 3; CH3); 2.20 (m, 2; H and H8); 2.07 (m, 2; H2 and H7);

1.60-2.10 (m, 2; H9 ex and H 0 exo); 0.90-1.40 (m, 2;

H9 endo and H10 endo) The mass spectrum (70eV) had m/e

390 (M', 0.1%), 218 (15.5%), 186 (19.6%), 155 (22.9%), 92

(28.3%), 91 (100%), and 31 (88.1%).

Anal.: Calcd. for C21H26SO5: C, 64.59; H, 6.71; S, 8.21

Found: C, 64.56; H, 6.74; S, 8.16









Preparation of anti-12-methoxyl-endo, exo, anti-tetracyclo-

[6.2.1.13'6.02'7]dodec-4-en-ll-yl-p-methylbenzenesulfonate

(70)-OTs


In a typical reaction the alcohol (70i-OII, 0.250 grams

(1.212 mmoles), was dissolved in the minimum amount of dry

pyridine (63 drops) and the mixture placed in an ice bath.

Freshly recrystallized p-methylbenzenesulfonyl chloride,

0.462 grams (2.424 mmoles), was slowly added to the chilled

flask followed by 49 drops of anhydrous pyridine to com-

pletely dissolve everything. The flask was tightly stop-

pered and maintained at 100C for 35 hours. The mixture was

then poured into 100 mL of ice and water, stirred for 10

minutes and filtered to yield a beige solid. The solid was

washed with 25 mL of cold water and then dried under vacuum

(0.1 torr) for 4-8 hours. The beige solid was dissolved in

benzene and treated with activated charcoal. After filtra-

tion through a celite pad and removal of the solvent under

reduced pressure the product was recrystallized from benzene/

hexane to yield white needles. After drying at room tem-

perature under vacuum (0.1 torr) for 6 hours 0.402 grams

(92.2%) of white needles were obtained, m.p. 114-116C (d).

The 1Hnmr spectrum (CDCl ) exhibited the following resonances:

6 7.76 (d, 2; aromatic protons); 7.32 (d, 2; aromatic pro-

tons); 6.02 (t, 2; H4 and H5); 5.45 (broad s, 1; H11); 3.30

(s, 3; OCH3); 2.76 (m, 2; H2 and H6); 2.48 (s, 3; CH3);

2.03-2.2 (m, 4; H1, H2, H7 and H8); 1.6-2.1 (m, 2; 19 exo









and H10 exo); and 0.85-1.6 H9 endo and H10 endo). The mass

spectrum (70 eV) had m/e 360 (M 0.3%), 241 (1.5%), 205

(10.7%), 188 (68.9%), 155 (44.5%), 129 (39.6%), 117 (46.8%),

97 (50.5%), and 91 (100%).

Anal.: Calcd. for C20 124SO4: C, 66.64; H, 6.71;

S, 8.89

Found: C, 66.91; H, 6.80; S, 8.74


Preparation of syn-12-methoxyl-endo, exo, anti-tetracyclo-

[6.2.1.1 '6.02'7]dodec-4-en-ll-yl-p-methylbenzenesulfonate

(69)-OTs


In a typical reaction the alcohol (6_)-OTs, 0.360

grams (1.743 mmoles), was dissolved in the minimum amount

of dry pyridine (2.5 mL) and the mixture placed in an ice
22
bath. Freshly recrystallized p-methylbenzenesulfonyl
22b
chloride, 0.6646 grams (3.486 mmoles), was slowly added

to the chilled flask followed by 3.5 mL of anhydrous pyri-

dine to completely dissolve everything. The flask was

tightly stoppered and kept at 100C for 65 hours. The mix-

ture was then poured into 100 mL of ice and water, stirred

for 15 minutes and filtered to yield a beige solid. The

beige solid, 0.520 grams (82.8%) was dried at room tempera-

ture under vacuum (0.1 torr) for 4 hours. It was dissolved

in benzene, treated with activated charcoal, filtered through

a celite pad and most of the solvent removed under reduced

pressure. Recrystallization from benzene/hexane yields






75

0.490 grams (78%) of white solid, m.p. 109-1110C. The IHnmr

spectrum (CDC13) exhibited the following resonances: 6 7.76

(d, 2; aromatic protons); 7.30 (d, 2; aromatic protons);

6.00 (m, 2; 114 and I 5); 5.51 (broad s, 1; fill); 3.37 (broad

s, 1; I112); 3.14 (s, 3; OCI3) ; 2.92 (m, 2; 113 and II6; 2.45

(s, 3; CH3); 2.04 (m, 4; If2, 17, l1, and H8 ); 1.6-2.1 (m, 2;

H9 exo and H10 ); 0.85-1.6 (m, 2; H9 endo and H0 endo).
9 exo 10 exo 9 endo 10 endo
The mass spectrum (70 eV) had m/e 360 (M 0.2%), 243 (1.1%),

188 (29.1%), 155 (23.0%), 129 (40.0%), 117 (40.3%), 115

(44.3%), 91 (100%), 77 (38.8%) and 43 (53.6%).

Anal.: Calcd. for C20 I24SO4: C, 66.64; H, 6.71; S,

8.89

Found: C, 66.74; H, 6.85; S, 8.79


Preparation of endo, exo, anti-tetracyclo[6.2.1.1 .02 ']-

dodec-4-en-ll-ol-12-one (64)-OH


In a typical reaction the alcohol (63)-OH, 200 grams

(8.46 mmoles), was dissolved in the minimum amount of ether

and added to 100 mL of 5% aqueous sulfuric acid.1 The

mixture was stirred at room temperature for 8 hours and then

extracted with 2 x 100 mL of ether. The combined ether

phases were washed with 100 mL of 10% sodium carbonate,

dried with anhydrous magnesium sulfate, filtered, and the

ether removed by rotary evaporation to give 1.45 grams

(90%) of crude alcohol. The crude product was recrystal-

lized from hexane to yield 1.20 grams (75%) of white

needles, m.p. 108-110C (dec) (lit. 103-105C (dec).15








The infrared spectrum (KBr) contained the following absorp-

tions: 3180 (s), 2810 (s), 1770 (s), 1745 (s), 1540 (s),

1070 (s), and 740 (s) cm-1. The 1Hnmr spectrum (CDC13)

contained the following resonances: 6 6.55 (5, 2; J=2.3 Hz,

114 and 115); 4.85 (broad s, 1; 1il1); 3.05 (m, 2: J=2.3 IIz,

113 and 116); 2.62 (broad s, 1; 011); 2.29 (m, 2; H2 and 119);

2.14 (m, 2; H1 and Hg); 1.55-2.20 (m, 2; H9 exo and

H10 exo); and 0.80-1.50 (H9 endo and 10 endo). The mass

spectrum (70 eV) had m/e 190 (M+, 0.1%), 162 (M+-CO, 9.8%),

129 (15.1%), 105 (100%), 91 (26.5%), 84 (58.2%), and 78

(25.8%).


Preparation of endo, exo, anti-tetracyclo[6.2.1.13'6.02'7]-

dodec-4-en-12-one-ll-yl-p-methylbenzenesulfonate (64)-OTs


In a typical reaction the alcohol (64)-OH, 0.839 grams

(4.41 mmoles), was dissolved in dry pyridine (63 drops) and

the mixture placed in an ice bath.22 Freshly recrystallized

p-methylbenzenesulfonyl chloride,22b 1.68 grams (8.82

mmoles) was slowly added to the ice cold flask followed by

77 drops of dry pyridine to completely dissolve everything.

The flask was tightly stoppered and placed in a refrigerator

for 24 hours. The mixture was then poured into 100 mL of

ice and water, stirred for 10 minutes and filtered to yield

a beige solid. The beige solid, 1.35 grams (88.8%) was

dried at room temperature (0.5 torr) for 4 hours. It was

dissolved in benzene, treated with activated charcoal,

filtered through a celite pad and most of the solvent








removed under reduced pressure. Recrystallization from

benzene/hexane yields 1.1 grams (72.3%) of white plates,

m.p. 125-1270C (dec). The 1Hnmr spectrum (CDC13) exhibited

the following resonances: 6 7.76 (d, 2; aromatic protons);

7.31 (d, 2; aromatic protons); 6.50 (t, s; J=2.3 Hz, H4 and

HS); 5.42 (broad s, 1; 11 ); 3.02 (m, 2; J=2.3 Hz, H and

H ) ; 2.48 (s, 3; CH3); 2.28 (m, 4; H1, H2, H7 and H );

1.65-2.18 (m, 2; H exo and H exo; and 1.00-1.50 (m, 2;

H9 endo and H0 endo). The mass spectrum (70 eV) had m/e

316 (M+-CO, 1.2%), 144 (41.6%), 129 (40.0%), 91 (50.0%),

79 (73.5%), 78 (100%), and 66 (50.8%).

Anal.: Calcd. for C19H20SO4: C, 66.27; H, 5.85;

S, 9.29

Found: C, 66.01; H, 5.88; S, 9.22


Preparation of 1,2,3,4-tetrachloro-5,5-diethoxycyclopenta-

1,3-diene (RO)


A two liter three-necked flask was fitted with a

mechanical stirrer, pressure equalizing funnel, and a reflux

condenser. To this flask was added 273 grams (1.0 mole) of

hexachlorocyclopentadiene (Aldrich H 600-2) and 500 mL of

95% ethanol. To this mixture was added a solution contai-

ning 140.3 grams (2.5 moles) of potassium hydroxide in

500 mL of 95% ethanol. The rate of addition was regulated

so as to maintain gentle reflux. The mixture was stirred

at room temperature overnight and the precipitated potas-









sium chloride removed by filtration. The ethanol was

removed by distillation and 300 mL of water added to the

black oily residue. The organic and aqueous phases were

separated and the aqueous phase extracted with 5 x 100 mL

portions of methylene chloride. The combined extracts and

organic phase were dried over anhydrous magnesium sulfate

and the methylene chloride removed by distillation. The

remaining black oil was distilled under reduced pressure

(106-120C at 0.30 to 2.5 torr) to yield 93 grams (32%) of

pale yellow oil. The 1Hnmr spectrum (CC14) contained the

following resonances: 6 3.60 (q, 4;) and 1.22 (t,6;).


Preparation of 12,12-diethoxy-3,4,5,6-tetrachloro-endo,

exo, anti-tetracvclo[6.2.1.13'6.0'7 ]dodec-4-en-ll-yl

acetate (81)-OAc


In a typical reaction, 10.0 grams (0.066 moles) of

anti-7-norbornenyl acetate ( 2)-OAc and 23 grams (0.079

moles) of 1,2,3,4-tetrachloro-5,5-diethoxycyclopenta-l,3-

diene (80) was mixed with 14 mL of carbon tetrachloride in

a glass bomb. The bomb was placed in a dry ice/isopropanol

bath (-780C) and the contents frozen. The contents were

then pumped down to 0.5 torr while frozen and the mixture

allowed to warm to room temperature. This freezing and

pumping procedure was repeated two more times and then the

bomb was sealed under vacuum. The mixture was placed in

an oil bath and heated for 45 hours at 140C. The bomb was









opened and the carbon tetrachloride removed under reduced

pressure to leave a black tar. This black tar was dis-

solved in hot methanol and treated with activated charcoal.

After filtration through a celite pad, water was added to

the filtrate until it just became turbid. The mixture was

then set aside for crystallization of the product. Fil-

tration yielded 14 grams (48%) of white crystalline solid,

m.p. 135-1370C. The 1Hnmr spectrum (CDC13) exhibited the

following resonances: 6 4.80 (broad s, 1; H11); 3.92

(q, 2; methylene of anti-ethoxyl); 3.82 (q, 2; methylene

of syn-ethoxyl); 2.60 (s, 2; H2 and H7); 2.42 (m, 2;

J=2.0 Hz; H1 and H ); 1.98 (s, 3; O2CCH3); 1.90 (m, 2;

H9 exo and H0 exo); 1.20 (m, 2; H9 endo and H10 endo)

and 0.96-1.3 (m, 6; CH3 of ethoxyls).


Preparation of 12,12-diethoxy-3,4,5,6-tetrachloro-endo,

exo, anti-tetracyclo[6.2.1.13'6.02'7]dodec-4-en-ll-ol

(81)-OH


A three-necked round bottom flask was fitted with a

reflux condenser, magnetic stirrer, nitrogen inlet, and

placed in a dry ice/isopropanol bath. Into this flask was

placed 3.04 grams (0.08 moles) of lithium aluminum hydride

and 125 mL of anhydrous ether. A solution of the acetate,

14 grams (0.032 moles) in 150 mL of anhydrous ether, was

added to the stirred mixture over a one-half hour period.

Stirring was continued for two hours after the addition

was completed. Water (3.0 mL) was cautiously added and the









mixture warmed to room temperature. Aqueous sodium

hydroxide, 15%, (3.0 mL) was then added and also an addi-

tional 9 mL of water. The mixture was magnetically

stirred until no more white solid formed. The solid was

removed hy filtration and the other dried over anhydrous

potassium carbonate. After filtration the ether was

removed under reduced pressure to yield 11.0 grams (86%)

of pale-green oil. On sitting for a few hours, the oil

solidified into a white solid, m.p. 87-90C. The IHnmr

spectrum (CDC13) contained the following resonances:

S4.08 (broad s, 1; H 1); 3.92 (q, 2; methylene of anti-

ethoxyl); 3.82 (q, 2; methylene of syn-ethoxyl); 2.60

(s, 2; H2 and H ); 2.42 (m, 4; J=2.0 Hz; H1 and H ; 1.90-

2.10 (H9 exo and H10 exo); 1.12-1.21 (m, 6; CH3 of ethoxyls);

and 1.20 (m, 2; H9 endo and H0 endo).
9 endo 10 endo

Preparation of 12,12-diethoxy-endo, exo, anti-tetracyclo-

[6.2.1.1 36.02'7]dodec-4-en-ll-ol (82)-OH


Gassman's procedure of reductive dechlorination with

some modifications was used in this synthesis.34,35 A two

liter three-necked flask was equipped with a true-bore

stirrer, a pressure equalizing funnel and a condenser fit-

ted with a nitrogen inlet. To this flask was added 450 mL

of tetrahydrofuran, 26 grams (1.52 gram-atoms) of finely

chopped metallic sodium and 41.5 grams (0.56 moles) of

tert-butyl alcohol. This mixture was stirred and heated









to reflux and 11 grams (0.028 moles) of (81)-OH dissolved

in 350 mL of tetrahydrofuran was added dropwise over a 1

hour period. The mixture was refluxed and stirred for 12

hours after the addition was completed, cooled to room

temperature and the metallic sodium removed by filtration

through a wire screen. Water (350 mL) was added to the

filtrate to dissolve the sodium salts. The aqueous and

ether phases were separated and the aqueous phase extracted

with 2 x 100 mL portions of ether. The combined ether

phases were dried over anhydrous magnesium sulfate and the

ether removed under reduced pressure to yield 4.5 grams

(60.8%) of white crystals, m.p. 78-810C. Recrystallization

from hexane yields a fluffy white solid, m.p. 104-1050C.

The 1Hnmr spectrum (CDC13) exhibited the following reso-

nances: 6 6.13 (t, 2; H4 and H ) ; 4.98 (broad s, 1; H 1);

3.40 (m, 4; CH2 of ethoxyls); 2.86 (p, 2; H3 and H );

2.23 (m, 2; HI and HS); 1.96 (m, 3; H2, H7 and OH); 1.5-

2.05 (m, 2; H9 exo and H10 e); 0.96-1.3 (m, 6; CH3 of

ethoxyls, H9 endo and HI0 eno). The mass spectrum (70 eV)

had m/e 264 (Mi, 31.7%), 219 (17.4%), 189 (44.5%), 161

(60.4%), 143 (94.6%), 123 (43.6%), 105 (78.5%), and 91

(100%).









Preparation of 12,12-diethoxy-endo, exo, anti-tetracyclo-

[6.2.1.1 3.027 ]dodec-4-en-ll-yl triethylsilvl ether

(82)-OSiEt3


In a typical reaction 1 gram (3.783 mmoles) of

(82)-OH was added to a round bottom flask and enough

dimethyl formamide (3.5 mL) added to dissolve everything.

Triethyl amine, 0.574 grams (5.675 mmoles) was added and

the flask placed in an ice bath. Triethylchlorosilane,

0.684 grams (4.540 mmoles) was added and caused the forma-

tion of a thick paste. An additional 3.5 mL of dimethyl

formamide was added to facilitate mixing and the mixture

shaken for 20 minutes at room temperature. The paste was

washed with 3 x 20 mL of anhydrous ether and these washings

passed through a short column of Alumina to remove the

last remnants of dimethyl formamide. The solution was

dried over anhydrous sodium sulfate and the solvent removed

under reduced pressure to yield 1.432 grams (90.8%) of

light brown oil. The 1Hnmr spectrum contained the follow-

ing resonances: 6 6.12 (t, 2; H4 and H5); 4.94 (broad s,

1; H11); 3.20-3.70 (m, 4; methylene of ethoxyls); 2.86

(m, 2; H3 and H6); 2.20 (m, 2; H1 and H8) 1.75-2.05 (m, 2;

H9 exo and H10 exo); 0.22-1.4 (m, 17; methyls of ethoxyls,

H9 endo and H10 endo' and ethyls attached to silicon).


1









Reduction of 12,12-diethoxy-endo, exo, anti-tetracyclo-

[6.2.1.1 36.02'7]dodec-4-en-ll-yl triethylsilyl ether

(82)-OSiEt3 with a 2:1.5 Molar Ratio of Aluminum

Chloride/Triethylsilane


A three-necked 250 mL round bottom flask was equipped

with a pressure equalizing funnel, and a reflux condenser

with a nitrogen inlet. The flask was immersed in an ice

bath and 0.916 grams (6.868 mmoles) of anhydrous aluminum

chloride was added and immediately covered by 50 mL of

anhydrous ether. Triethylsilane, 0.599 grams (5.151 mmoles),

was dissolved in 35 mL of anhydrous ether and added to the

flask. The combined mixture was stirred for 15 minutes

at ice temperature. Addition of the silated ketal (82)-

OSiEt3, 1.30 grams (3.434 mmoles), dissolved in 35 mL of

ether immediately results in a pale red solution. The

solution was stirred at room temperature for 7 hours after

the addition was completed. The flask was chilled and 50 mL

of saturated aqueous ammonium chloride added followed by

50 mL of water. A milky white ether phase results and

dissipates on stirring to give a clear solution. The aque-

ous and ether phases were separated and the aqueous phase

extracted with 2 x 25 mL of ether. All ether phases were

combined and washed with 20 mL of saturated aqueous sodium

bicarbonate solution and then dried over 50/50 anhydrous

potassium carbonate/magnesium sulfate. After filtration

and removal of solvent by rotary evaporation 1.02 grams








(88.8%) of brown oil. 1Hnmr spectroscopy reveals that two

products are present. The oil contained approximately 95%

of the anti-ethoxyl isomer and 5% of the syn-methoxyl

isomer. Separation of these isomers was achieved by chro-

matoqraphy on freshly dried Silica Gel or Silicar CC-7

using a 50/50 Hexane/Ether solvent mixture. Desilylation

was achieved by treatment with tetrabutylammonium fluoride

in THF7b,38 to yield the corresponding alcohols, (83)-OH

and (84)-OH. The anti-ethoxyl isomer (69)-OH exhibited

the following resonances in its 1Hnmr spectrum (CDC3) :

6 6.05 (5, 2; H4 and H5) ; 4.80 (broad s, 1; Hl); 3.38

(q, 2; CH2 of ethyl); 3.36 (m, 1; H12); 2.15 (t, 2; H3 and

H6); 1.99 (s, 3; H2, 7 and OH); 1.67-2.15 (m, 4; H1, HB,

H9 exo and H10 exo); 1.17 (t, 3; CH3 of ethyl); and 0.8-

1.4 (m, 2; H9 endo and H10 endo). The mass spectrum (70 eV)

had m/e 220 (M+, 3.5%), 174 (10.0%), 143 (16,8%), 91

(100.0%), 83 (30.8%) and 59 (69.7%).



Kinetic Studies


Preparation of kinetic solutions


Preparation of acetic acid for kinetic solutions.

Reagent grade acetic acid, 2500 mL was placed in a 3 liter

flask with 0.1 mole of sodium acetate and 50 mL, approxi-

mately 2%, of acetic anhydride. This mixture was refluxed

for 7 hours, distilled, and stored in a dry atmosphere.42








Preparation of standard perchloric acid. The standard

perchloric acid titrant was prepared by adding 6.8 grams

of 60-62% perchloric acid (Mallinkrodt) and 18 mL of acetic

anhydride to a two liter volumetric flask and diluting the

mixture to the mark with reagent grade glacial acetic acid.

The mixture was maintained at room temperature for 24 hours
41
before it was used.41 This solution was standardized

against primary standard potassium hydrogen phthalate using

a bromophenol blue endpoint. The normality of the solution

was 0.02277 N and remained constant throughout the kinetic

studies.

Preparation of standard sodium acetate. The standard

sodium acetate titrant was prepared by adding 2.12 grams

(0.02 moles) of primary standard anhydrous sodium carbonate

to a two liter volumetric flask and then adding anhydrous

glacial acetic acid up to the mark. The solution was held

at room temperature for 24 hours before standardization

was attempted.41 This solution was standardized against

the standard perchloric acid using a bromophenol blue

endpoint. The normality of the solution was 0.02024 N and

remained constant throughout the kinetic studies.

Preparation of the acetic acid kinetic solution. The

acetic acid kinetic solution was prepared by adding 3.183

grams (0.0300 moles) of sodium carbonate to a volumetric

flask and adding anhydrous acetic acid up to the 2 liter

mark. This solution was held at room temperature for 24









hours and then standardized against the standard perchloric

acid using a bromophenol endpoint. The normality of the

solution was 0.02879 N and was assumed to remain constant

throughout the kinetic studies.

Calibration of constant delivery pipets.42 A 5 mL

constant delivery pipet was filled with anhydrous kinetic

acetic acid and the acid delivered into a tared 50 mL

erlenmeyer flask. The acid was found to weigh 5.2418

grams. The temperature was 230C and the density of acetic

acid is 1.0491 g/mL at 200C. The inverse of the density

measurement is 0.9532 mL/gram and multiplying this value

by the number of grams of acetic acid delivered by the

pipet yields a volume of 4.9965 mL. The coefficient of

expansion of acetic acid is 0.11% per degree Celsius. A



Temperature Correction= V -[V x[(T2-T ) x 0.0011]]


= 4.9800 mL at 200C



constant delivery pipet of about three mL was calibrated

by the same method as described here and found to deliver

at 20C, 3.070 mL of acetic acid.

Preparation of bromophenol blue indicator solution.

The indicator for the acetic acid kinetics was prepared by

adding 0.1 grams of bromophenol blue and 1.0 mL of acetic

anhydride to 100 mL of acetic acid and using the saturated

which resulted.









Kinetic procedures


Acetic acid kinetics of all tosylates. A carefully

weighed sample of R-OTs was added to a 25 mL or 50 mL

volumetric flask and then dissolved in 25 mL or 50 mL of

0.02879 N sodium acetate in acetic acid containing 2%

acetic anhydride.43 This concentration of R-OTs afforded

a solution of approximately 0.01 M in tosylate. The

volumetric flasks were then stoppered and placed in either

a silicon oil bath or water bath. These baths were heated

in conjunction with a Yellow Springs Instrument Company

probe and Model 72 Proportional Temperature Controller.

After an equilibration time of 5 to 15 minutes, the first

aliquot was removed and analyzed. This aliquot was arbi-

trarily taken as the zero point. The infinity point was

taken after 8-10 half-lives.

Each run was analyzed by adding a 4.980 mL or 3.070

mL aliquot to 6.30 mL or 3.88 mL of 0.02277 N perchloric

acid respectively and 7-10 drops of bromophenol blue

indicator. This mixture was titrated with 0.02024 N sodium

acetate solution to the first appearance of a permanent

yellow color.


Analysis of data


The observed infinity titers were used to calculate

the amount unreacted for all of the sulfonate esters. In

runs where the infinity titer was smaller than that observed

for another run of the same compound, the larger infinity









titer was used. The following equation was used to calcu-

late the amount unreacted. The natural logarithm was taken




mL NaOAc mL NaOAc
amount unreactod = at at time
mL NaOAc mL NaOAc
at at zero time



of the resulting value to obtain -In(amount unreacted).

Each specific rate constant was obtained by dividing the

-Zn(amount unreacted) by the appropriate time in seconds.

The data are presented for each run in the following

tables, along with the concentration of the ester, the

concentration of the kinetic solution, the concentration

of the titrant and the temperature of the bath. The half-

life was obtained by dividing Zn 2 by the rate constant k.



















M r- D O -H
C00 N, ormmmNo
0 000000















0 0 C00 0


0 0 0 0000


SocH N L mo





o o 0c, 0 H cH







O D C0 C-- CD
.N .00000 .
000000000







00000000
000000000




o Ln o o o o


000000 O0
-Z 0 3' 0) 1, 0 r- --i L0 00
Ln r- co C) (1 Lrn o co 'A IQ.

0000000-0-0(N





000000000
OO000000000
Hn L0n0 r) cn Ln 0 mo Ln t
- CN M rH- O CN L CN >




H-0 0 -- f-1 N 0 4-
0






H N M -T Ln k 9 o a -

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