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Xerox University Microfilms 300 North Zaeb Road Ann Arbor, Michigan 48106 I I 75-26,677 VALGHO, Joseph James, 1948- REACTIONS OF CRGANOLIIHIUMS. WITH A VARIETY OF VINYL CHLORIDES.

The Ohio State University, Ph.D., 1975 Chemistry, organic

j Xerox University Microfilmsr Ann Arbor, Michigan 48106

THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED. REACTIONS OF ORGANOLITHIUMS WITH A

VARIETY OF VINYL CHLORIDES

DISSERTATION

Presented in Partial Fulfillment of the Requirements for

the Degree Doctor of Philosophy in the Graduate

School of The Ohio State University

Joseph James Valcho, B.S.

* * * * «■

The Ohio State University

1975

Reading Committee: Approved By

Paul G. Gassman John S. Swenton John A. Secrist, III

Advisor Department of Chemistry ACKNOWLEDGMENTS

The author would like to thank Dr. Paul G. Gassman for his patience and prodding during the course of this research. His high scientific ideals are contagious and collaboration with him has been an intellectually stimulating experience.

Mr. George Rowse is gratefully acknowledged as a spark during the author's early exposure to science. Thanks are extended to Dr.

Toby Chapman for his good counsel while the author was an undergraduate at the University of Pittsburgh. The author would like to thank his parents for their encouragement and concern during his education.

The author would also like to thank Tom and George for their lessons in good lab technique.

How my wife, Jeannie, put up with the author during these years is a mystery, but he is eternally grateful for her cheerful support.

Her love is soothing— she makes me smile.

ii VITA.

October 3, 1 9 4 8 ...... Born - Aliquippa, Pennsylvania

1970 ...... B. S., University of Pittsburgh, Pittsburgh, Pennsylvania

1970-1973...... Teaching Associate, The Ohio State University, Columbus, Ohio

1975-1975 ...... Research Associate, The Ohio State University, Columbus, Ohio

FIELD OF STUDY

Major Field: Organic Chemistry

iii TABLE OF CONTENTS

Page

ACKNOWLEDGMENTS...... ii

VITA ...... iii

LIST OF TABLES ...... xi

INTRODUCTION ...... 1

THE PROBLEM...... 12

RESULTS AND DISCUSSION...... 13

The Reactions of 3-Chlorobicyclo[3* 2. l]oct-2-ene (37) ..... 13

The Reactions of 2-Chlorobicyclo[3.2. l]oct-2-ene ( 64)..... 21

Sie Deuterated Chlorobicyclo[3.2. l]oct-2-enes...... 27

The n-Butyllithium Reaction of 2r-Chloronorbornene ( 4 ) ...... 37

The Methylated Chlorobicyclo[3«2.l]oct-2-enes...... 49

Reactions of l-Chloro-2-Alkylcyclohexenes ...... 53

The n-Butyllithium. Reaction of l-Chloro-2-vinylcyclohexene (1 92) ...... 66

Reactions of 2-Chloromethylenenorbornane ...... 69

SUMMARY...... 76

EXIERIMENTAL...... ? 78

3-Chlorobicyclo[3.2.l]oct-2-ene (3 7 ) ...... 78

Reaction of 3-Chlorobicyclo[3.2. l]oct-2-ene (37) with n-Butyllithium...... 78

Bicyclo[3* 2. l]octan-3-one (42) ...... 79

iv Page

3-n-Butylbicyclo[3.2.l]octan-3-ol (43) ...... 80

3-n-Butylbicyclo[3.2.l]oct-2-ene (4o) ...... 8l

exo-2-n-Butylbicyclo[3«2.1]octan-2-ol (45) .... 8l

exo-2-n-Butylbicyclo[3.2. l]oct-2-ene (4l) ...... 82

Reaction of 3-Chlorobicyclo[3»2.l]oct-2-ene (37) with Hienyllithium ...... 82

Reaction of 3-Chlorobicyclo[3.2.l]oct-2-ene (37) with Methyllithium...... 84

exo-3 -Fhenylbicycio[3 .2. l] octan-3-ol (30) ...... 85

3 -Ihenylbicyclo[3 .2 . l]oct-2-ene (46) ...... 85

exo-2-Hienylbicyclo[3.2 . l]octan-2 -ol (51) ...... 86

2-Rienylbicyclo[3 .2 . l]oct-2 -ene (47) ...... 86

exo-3 -Methylbicyclo[3 .2 . l]octan-3 -ol (5 2) ...... '. 87

3-Methylbicyclo[3. 2. l]oct-2-ene (48) ...... 88

exo-2-Methylbicyclo[3.2.l]octan-3-ol (5 5) ......

2-Methylbicyclo[3.2. l]oct-2-ene (49) ...... 89

2,2-Dichlorobicyclo[3-2.l]octane (65) ...... 89

2-Chlorobicyclo[3.2. l]oct-2-ene (64) ...... 90

Reaction of 2-Chlorobicyclo[3.2.l]oct-2-ene (64) with n-Butyllithium...... 91

Reaction of 2~Chlorobicyclo[3.2.l]oct-2-ene (64) with n-Butyllithium Followed by Quenching with Deuterium Oxide .. 91

Reaction of 2-Chlorobicyclo[3.2.l]oct-2-ene (64) with Phenyllithium...... 92

Reaction of 2-Chlorobicyclo[3.2. l]oct-2-ene (64_) with Hienyllithium Followed by Quenching with Deuterium Oxide ... 93

v Page

Reaction of 2-Chlorobicyclo[3.2.l]oct-2-ene (64) with Methyllithium...... 93

Reaction of 2-Chlorobicyclo[3.2. l]oct-2-ene (64) with Methyllithium Followed by Quenching with Deuterium Oxide ... 94-

Reaction of 3-Chlorobicyclo[3.2.l]oct-2-ene (3 7 ) with n-Butyllithium Followed by Deuterium Oxide Quenching...... 94

Reaction of 3-Chlorobicyclo[3.2. l]oct-2-ene (37) with Fhenyllithium or Methyllithium, Followed by Deuterium Oxide Quenching...... 95

Control Reaction of the 3- and 2-n-Butylbicyclo[3.2.1]- oct-2-enes (40 and 4-1) with n-Butyllithium Followed by Deuterium Oxide Quenching...... 95

Bicyclo[3.2.l]octan-3-one-2,2s4-,4-d4 (7 9) ...... 96

3 ,3 -Dichlorobicyclo[3 .2 .1 ]octane-2 ,2 ,4,4-d4 (8 0) ...... 97

3-Chlorobicyclo[3.2. l]oct-2-ene-2,4,4-d3 (77)...... 97

Bicyclo[3.2.l]octan-2-one-3,3-d2 (8l) ...... 98

2,2-Dichlorobicyclo[3.2. l]octane-3,3-d2 (8 2) ...... 98

2-Chlorobicyclo[3« 2. l]oct-2-ene-3-d (7 8) ...... 99

Reaction of 3-Chlorobicyclo[3.2. l]oct-2-ene-2,4,4-d3 (77) with n-Butyllithium...... 100

Reaction of 2-Chloro-3-deuteriobicyclo[3. 2.l]oct-2-ene (7 8) with n-Butyllithium...... 101

Reaction of 3~Chlorobicyclo[3.2. l]oct-2-ene-2,4,4-d3 (77) with Fhenyllithium...... 102

Reaction of 2-Chloro-3-deuteriobicyclo[3-2.l]oct-2-ene (7 8) with Phenyllithium...... 103

Reaction of 3-Chlorobicyclo[3.2.l]oct-2-ene-2,4,4-d3 (77) with Methyllithium...... 104

Reaction of 2-Chloro-3-deuteriobicyclo[3.2. l3oct-2-ene (7 8) with Methyllithium...... 105

vi Page

Reaction of 2-Chloronorbornene (^) with n-Butyllithium Followed by Deuterium Oxide Quenching ...... 106

2-Chloronorbomene-3-d (97)...... 107

Reaction of 2-Chloronorbornene-3-d (97) with n-Butyl- lithium...... 107

Control Reaction of 2-n-Butylnorbornene (102) with n- Butyllithium Followed by Deuterium Oxide Quenching ..... 109

(+)-(l£)-2-Chloronorbomene (ll4) ...... 109

Reaction of (+)-(ls)-2-Chloronorbornene (ll4) with n-Butyllithium ....;...... 110

Hydrogenation of 2-n-Butylnorbornene (121 and 122) ...... Ill

(+)-(3S)-2-Butylidenenorbomane (124) ...... 112

(-)-(lS)-(2R)-endo-2-n-Butylnorbomane (123) ...... 112

3 -Chloro-4-exo-hydroxybicyclo[3.2.l]oct-2-ene (133 )•...... 113

3-Chlorobicyclo[3.2. l]oct-2-ene-4-one (134) ...... 113

3-Chlorobicyclo[3.2.l]octan-2-one (13 3 ) • • • H4-

3-Chloro-2-exo-methylbicyclo[3.2.l]octane-2-ol (136) ...... 115

3-Chloro-2-methylbicyclo[3.2.l]octene-2 (131) ...... 115

2-Ethylidenenorbornane (137) ...... H 6

3-Methylbicyclo[3.2.l]octan-2-one (1 3 8 ) ...... 117

2,2-Dichloro-3-methylbicyclo[3.2.1]octane (139) •••••...... 117

2-Chloro-3-methylbicyclo[3*2.l]octene-2 (132 ) ...... 118

Reaction of 2-Chloro-3-methylbicyclo[3.2.l]oct-2-ene (132 ) with n-Butyllithium ..... 119

Reaction of 3-Chloro-2-methylbicyclo[3.2. l]oct-2-ene (l^l) with n-Butyllithium ...... 119

vii Page endo-4-n-Butyl-3,3-dichlorotricyclo[4.2.1.02s 4]nonane (l42a) and 2-n-Butyl-3,3-dichlorotricyclo[4.2.1.02»4]nonane (lg2b) ...... 120 endo-4-n-Butyltrieyclo[4.2.1.0g? 4]nonane (143) and 2-n- Butyltricyclo[4.2.1.02»4]nonane (144) ...... 122

Reaction of 3_Chloro-2-methylbicyclo[3«2. l]oct-2-ene (131) with Ehenyllithium...... 123

Reaction of 2-Chloro-3-methylt>icyclo[3.2.l]oct-2-ene (1 3 2 ) with Ehenyllithium...... 124

Reaction of 3-Chloro-2-methylbicyclo[3.2.l]oct-2-ene (131) with Methyllithium...... 125

Reaction of 2-Chloro-3-methylbicyclo[3.2.l]oct-2-ene (132) with Methyllithium...... 126 trans -1,2-Dichloromethylcyclohexane (1 5 2) ...... 126 l-Chloro-2-methylcyclohexene (145.)...... 127

She Reaction of l-Chloro-2-Methylcyclohexene (l45) with n-Butyllithium...... 128

1-n-Butylnorcarane (15 4 ) ...... 129 l-n-Butyl-2-methylcyclohexanol (157) ...... 130 l-n-Butyl-2-methylcyclohexene (155) ...... 131

The Reaction of l-Chloro-2-methylcyclohexene (145) with Hienyllithium...... 132

Reaction of l-Chloro-2-methylcyclohexene (145) with Methyllithium...... 132

1-Methylnorcarane (159) ...... 135 l-Methyl-d3-cyclohexanol (l6l) ...... 134 l-Methyl-d3-cyclohexene (l6 2 ) ..... 134 trans-1,2-Dichloro-l-methyl-d3-cyclohexane (2l6) ...... 135

viii Page l-Chloro-2-methyl-d3-cyclohexene (l6o) ...... 135

Hie Reaction of l-Chloro-2-methyl-d3-cyclohexene (l6o) with n-Butyllithium...... 136

Reaction of l-Chloro-2-methyl-d3-cyclohexene (l6o) with Methyllithium...... 137

Hie Reaction of l-Chloro-2-methyl-d3-cyclohexene (l60) with Hienyllithium...... 138

Preparation of trans-l,2-Dichloro-l-ethylcyclohexane (217) ...... 139 l-Chloro-2-ethylcyclohexene (178) ...... 140

Reaction of l-Chloro-2-ethylcyclohexene (178) with n- Butyllithium...... 1^1

Preparation of 2-Ethylcyclohexanone (219) ...... 1^-3

Preparation of the Epimeric l-n-Butyl-2-ethylcyclohexanols (220) ...... 1 ^

1-n-Butyl-2-ethylcyclohexene (l80) ...... 1 ^

2-n-Butyl-2-chlorocyclohexanone (22l) ...... 1^-5

2-n-Butylcyclohexenone (1 83 ) ...... 1^6

Diethyl(3-ethyl-2-n-butylcyclohexene)phosphate (1 8 5) ...... 1^7

Preparation of 2-n-Butyl-3-ethylcyclohexene (l8l) ...... 148

Reaction of l-Chloro-2-ethylcyclohexene (178) with Hienyllithium...... 1^8

Reaction of l-Chloro-2-ethylcyclohexene (1 7 8) with Methyllithium...... 150

1-Ethyl-2-methylcyclohexene (1 8 8) ...... 151

2-Chlorocyclohexenecarhoxaldehyde (1 9 3 ) ...... 151 l-Chloro-2-vinylcyclohexene (192) ...... 152

ix Page

Reaction of 2-Chloro-l-vinylcyclohexene (192) with n- Butyllithium...... 153

3-Hexylidenecyclohexene (194) ...... 154

Chloromethylenenorbornane (19 9 ) ...... 154

Reaction of 2-Chloromethylenenorbomane (199) with n- Butyllithium...... 155

2-Pentylidenenorbomane (200) ...... 156

Reaction of 2-Chloromethylenenorbomane (199) with Fhenyllithium...... 157

E- and Z-2-Benzylidenenorbornanes (201 and 202) ...... 158

Reaction of 2-Chloromethylenenorbornane (199) with Methyllithium...... 159

Reaction of 2-Chloromethylenenorbornane (l99) with n- Butyllithium Followed by Quenching withDeuterium Oxide .... 160

Control Reaction of 2-Pentylidenenorbornane (200) with n-Butyllithium Followed by Deuterium OxideQuenching ...... l6l

Reaction of 2-Chloromethylenenorbomene (199) with Hienyllithium and Methyllithium Followed by Deuterium Oxide Quenching...... l6l

REFERENCES ...... 162

X LIST OF TABLES

Table Page

I Summary of Results of the Organolithium Reactions of 37, and 6 ^ ...... 22

II Organolithium Reactions of 3-Chlorobicyclo[3»2.1]- oct-2-ene-2,4,4-d3 (77) and 2-Chlorobicyclo[3. 2.1]- oct-2-ene-3-d (Jo) ...... 3 0 -3 1

Ill Products and Isotope Distribution from the Reactions of l-Chloro-2-methyl-d3-cyclohexene (l6o) with Organolithiums...... 38

xi INTRODUCTION

In the course of research involving the question of the classical

or non-classical nature of the 7-norbornenyl cation, Gassman and 1 Patton had need for certain methylated norbomene derivatives. No

useful routes to compounds such as 1 existed in the literature. Syn-

thetic sequences involving carbonium ion intermediates are unsuitable,

as illustrated by the fact that exo-2-methylnorbornane-2 -ol (2 ) on

treatment with acid gives mainly 2-methylenenorbornane (3 ), along 2 with 1-methylnorbomene, rather than 2-methylnorbornene (l, X=H).

(1) P. G. Gassman and D. S. Patton, J. Amer. Chem. Soc., 91? 2160 (1969).

(2) M. Rei and H. C. Brown, ibid., 8 8, 5335 (1966); J* A. Berson, et.al., ibid., 8 9. 2590 (1 9 6 7), and references therein.

1 2 3

Thus these workers began an investigation of the reaction of 2-chloronorbornene (k) and derivatives with organolithium reagents in the hope

1 of forming 1, with the positional integrity of the double bond intact.

They found that treatment of with methyllithium in ether at 25° for 3 8 days gave a 73% yield of 1, X=H. This reaction was studied in 4 detail by Atkins. Following these results, a suitable precursor

(3) P« G. Gassman, J. P. Andrews, Jr., and D. S. Patton, Chem. Commun., ^37 (l9&9)-

(4) T. J. Atkins, Ph.D. Thesis, The Ohio State University, 1972.

4 1, X = H to anti-7-hydroxy-2-methylnorboraene (l, X=OH) seemed to be 2-chloro-

7,7-dimethoxynorbornene (5). However, reaction of 5^ with methyllithium in ether gave only 5% of 7,7-dimethoxy-2-methylnorbornene (6), the major product (5b-%) being the nortricyclene (j). The sensitivity of these

reactions to substituents was demonstrated, and the synthetic goal

achieved when it was shown that a mixture of the anti and syn-7-

hydroxy-2-chloronorbomenes (8_ and respectively) react with methyl

lithium to give the 2-methylnorbornene-7-ols, 10_ and 11, in 66% com

bined yield (contaminated with traces of 7-hydroxynorbornene and nor

tricyclene).

8 9 1 0 11

4 The scope of the reaction was further examined by Atkins. It

was found that the reaction of 5_ with n-butyllithium in hexane-ether

gave a 2:1 mixture of 2-n-butyl-7>7-dimethoxynorbornene (12) and 3-n-

butyl-7,7-dimethoxynortricyclene (13) in 88% yield. The reaction of ^

H 5 12 13 with phenyllithium in 7 0 :3 0 benzene-ether gave a 69% yield of 1: 9 mix- 4

ture of 3 -phenylnortricyclene (l4) and a compound identified as 5-

benzalbicyclo[2.1. l]hexane (15,). & Separation was accomplished, and

(5) (a) P. G. Gassman and T. J. Atkins, J. Amer. Chem. Soc. , 92, 5810 (19T0); (b) K. B. Wiberg, B. R. Lowry, and T. H. Colby, ibid., 8 3 , 3998 (1961).

a sample of 15, was hydroxylated (osmium tetroxide) and cleaved (periodic

acid) to afford a 67^ yield of 16. The five-step route to (and

structure proof of) l6_ from norcamphor gave an overall yield of 2QPjo.

This route to 16 provides an attractive alternative to the 11-step

> + Hi

H H 14 15 16

sb literature procedure. The reaction of phenyllithium with 5, again

illustrates the sensitivity of such reactions to substitution, in that

only syn-3 -phenyl-7,7-dimethoxynortricyclene (1 7) was obtained, in 8 yield.

cifeO- . OCIfe

Hi H 17 3 , 4 , 5 a Mechanisms for the ahove reactions have been postulated,

and they will be discussed in detail when pertinent. As outlined for

the vinyl chlorides described above, investigation in these labora

tories had been limited to reactions of the sensitive and geometrically unique 2-chloronorbornenes. Thus it was desirable to further measure the scope of these reactions of vinyl chlorides with organolithiums, by going to other systems, and undertaking mechanistic studies (and conjecture) where appropriate.

Some pertinent aspects of the chemistry of organolithium e reagents should be mentioned. An early example of the variety of paths available to organolithiums in their reactions with vinyl halides is provided by the reaction of p-bromostyrene (l8) with n-butyllithium. ■7a It was reported that treating l8_with n-butyllithium in petroleum ether for 38 days gave (3-n-butylstyrene (1 9) and 1,4-diphenylbutadiene

/ \ (20). Later this reaction was reinvestigated, and it was found7b that

(6) For reviews outlining the preparation, structure, and reactivity of organolithiums see: (a) R. J. Jones and H. Gilman, Organic Reactions, 6, 339 (1951); (h) H. Gilman and J. W. Morton, Jr., ibid., 87 25B (195^); (c) J. M. Mollan and R. L. Bebb, Chem. Rev., 6 % 693 (1 9 6 9); (d) T. L. Brown, Adv. Organometal. Chem. , 2j> 365 (I9 6 5)» C' Coates, M. L. H. Green, and K. Wade, *'Organometallic Compounds,'' Vol. I, 3rd ed., Metheun and Co., LTD, London, 1 9 6 7*

(7) (a) C. S. Marvel, F. D. Hager, and'D. Coffman, J. Amer. Chem. Soc., b9j 2323 (1927); (b) H. Gilman, W. Langham, and F. W. Moore, ibid., 62, 2327 (19^0). H Ph H n-Bu * > - 0 H Hi H Ph H

19 20

H,L Br H C02H / ■ \ Hi> = \ Hi NH

18 21

after shorter reaction times, quenching the reaction with carton dioxide gave 21. On the other hand on changing to ether as a solvent, quenching the n-butyllithium reaction of l8_with carbon dioxide now gave 22.

Product 19 from the reaction of 18 is an example of a coupling mechanism, that is, carbon-carbon bond formation occurring with for mation of lithium halide. Such a reaction can be of synthetic utility

(for example this may be the mode of formation of 10_ and 11 from 8_ and \ 6a g), or an interfering side reaction in the synthesis of an organolithium reagent itself. Coupling mechanisms have been the object of 8 considerable mechanistic interest, and have been studied using sa Chemically Induced Dynamic Nuclear Polarization (CIDNP) and label- sb, c ing.

(8) (a) For an excellent review see: H. R. Ward, R. G. Lawler, and R. A. Cooper in Chap. 7 of ''Chemically Induced Magnetic Polarization,'' A. R. Lepley and G. L. Closs, Eds., John Wiley and Sons, New York (1973); (t>) R* M. Magid, E. C. Nieh, and R. D. Gandour, J. Org. Chem., 36, 2099 (1971); (c) R. M. Magid and E. C. Nieh,~~ibid7, -3 6 , 2103 (1971).

The formation of trans-cinnamic acid (2l) on quenching requires 6a a second course involving the well-documented halogen-metal inter conversion reaction illustrated below. Reaction of the intermediate

H v Br H Li + n-BuLi ----- > /==< + n-BuBr ,X» Hi H

18 23 2k

(3-lithiostyrene (23 ) with carbon dioxide gives 21, while coupling of

23 and 2b_ provides an alternative source of 19,. Coupling of 23_ with l8 represents a rational path to 20. Halogen-metal interconversion sa reactions have also been the object of recent mechanistic interest.

Product 22_comes from the n-butyllithium functioning as a strong base, where dehydrobromination can be effected in two different ways, n a m e l y via a- or ^-elimination reactions. As illustrated in {3- elimination, hydrogen bromide is lost, either through the interme- 9a diacy of 2k (Elcb mechanism) or concertedly(E2). Rienylacetylene

(9) (a) G. Kobrich, Aigew. Chem. Internat. Edit., kj, k$ (1 9 6 5)*, (b) G. Kobrich, ibid. , 6, 41 (1967); (c) G. Kobrich, ibid., 11, 475 (1972).

H\ ^ r H>r> Br / = \ ► * HiC = CH -- > HiC = CLi Ph H Hi H 26

18 *****2k 25 I 22

5b, c (2 5) is thus formed and is itself metallated to give 26 . which is carbonated to give 22.

The second possibility, a-elimination, requires loss of the proton from the carbon atom bearing the bromide, to form the carbenoid

(27). Migration of phenyl (or hydrogen) would give 25; Carbenoids 9 such as 27 have been extensively studied by Kobrich. The rearrange-

Hv ,Br H /Br

Hf Li Hi Li ment of the type 27, to 25, (the Fritsch-Buttenberg-Wiechell rearrange- . 9b,c,io ment) is likewise well documented, and support for such a mechanism in the reaction of p-chlorostyrene (2 8) with phenyllithium li to give 25^has been presented. However a '’free'' carbenoid as 9b,C,12 illustrated by 27b is most likely not involved.

(10) D. Y. Curtin and E. W. Flynn, J. Amer. Chem. Soc., 8l, 4714 (l959)i Y. Curtin and W. H. Richardson, ibid., 8 1, 4719 (1959).

(11) S. J. Cristol and R. F. Helmreich, ibid., 77, 5034 (1955).

(12) D. Y. Curtin, E. W. Flynn, and R. F. Nystrom, ibid., 80, 4599 (1958); See also, D. Y. Curtin, J. A. Kampmeier, and B. R. O'Connor, ibid., 8 7, 863 (1 9 6 5).

When metal-halogen interchange occurs on treating gem-dihalides sb,c,13 with organolithiums, carbenoid intermediates are formed. As opposed to the case of vinyl carbenoids of the type illustrated by 27: saturated carbenoids such as 29, derived from benzoyl bromide (2 9) and / % 14a phenyllithium can be trapped by olefins (3 1 ) to give 3 2 . Intra-

(13) W. Kirrase, ''Carbene Chemistry,'' 2nd ed., pp 9 6-IO8 and 236 - 240, Academic Press, New York, 1971; G. Kobrich, Bull. Soc. Chim. France, 2712 (1 9 6 2).

(14) (a) G. L. Closs and R. A. Moss, J. Amer. Chem. Soc. , 86^ 4042 (1 9 6 ^); (b) For the intramolecular reaction of an alkenyl substituted carbenoid see: G. L. Closs and L. E. Closs, ibid., 85, 99 (1963). 10

u © © RiCHBr2 FhCHBr x

molecular reactions of suitably substituted carbenoids generated under similar conditions (particularly with methyllithium) have 15 proven of great utility in the synthesis of strained-ring compounds.

(15) W. R. Moore, H. R. Ward, and R. F. Merritt, ibid., 8 3 , 2019 (1 9 6 1); L. Skattebj^l, Tetrahedron Lett. , 2361 (19707; W. R. Moore, K. G. Taylor, and P. Muller, ibid., 2365 (1970).

Another type of reactivity exhibited by organolithiums is their 16 17 18, 19 ability to add to ethylene, conjugated dienes, and other olefins, as illustrated for the addition of n-butyllithium to norbornadiene isa (33) to give a 5:1:10 mixture of 3k? 35, and 3 6 . Unless the olefin

Li -Bu n-Bu + + © Li.©

a a a 11

(l6) (a) K. Ziegler and H.-G. Gellert, Justus Liebigs Ann. Chem., 5 6 7, (195 (see also pp 179 and 1 8 5) (1950); (b) P. D. Bartlett, S. Friedman, and M. Stiles, J. Amer. Chem. Soc., 75, 1771 (1953).

(IT) K, Ziegler, F. Dersch, and H. Wollthan, Justus Liebigs Ann. Chem. , 5J4L; 13 (1934); K. Ziegler, H. Wollthan, and A. Weriz, ibid. , 5JL1, 64 (1934); E. Grovenstein, Jr., and G. Wentworth, J. Amer. Chem. Soc. , 89; 1852 (1 9 67)', A. V. Tobolsky, Polymer Sci., 25; 2451 (1957).

(18) (a) G. Wittig and C. Hahn, Angew. Chem., 72; 781 (i9 6 0); (b) G. Wittig and J. Otten, Tetrahedron Lett., 601 (1 9 6 3).

(19) J. K. Crandall and A. C. Clark, ibid., 325 (19&9).

is activated to attack by strain (as is the case of 3 3 )> or substi- 16a, iv tution, addition of primary or aryllithiums is difficult. 16b Secondary and tertiary organolithiums are considerably more reactive.

Such an addition mechanism, followed by P-elimination of lithium bromide, could be an alternative to the coupling mechanism discussed for the formation of 19 from 18. THE PROBLEM

As discussed in the previous section, several unprecedented reactions had "been observed in these laboratories during studies of the organolithium reactions of various 2-chlorobicyclo[2.2.l]heptenes.

These observations showed that vinyl chlorides could undergo reactions other than a - or ^-elimination, where the organolithium reagent functions as a strong base.

It therefore seemed of interest to study other vinyl chloride systems, in order to gather additional mechanistic information and explore possible synthetic utility.

12 RESULTS AND DISCUSSION

The Reactions of 3-Chlorobicyclo[3.2.l]oct-2-ene (27). 3 , 4, 5 q , As briefly outlined, Gassman and coworkers have reported a number of unprecedented reactions in their study of the reactions of organolithiums with a variety of 2-chloronorbornenes. As was the case for the reactions of (3-br omostyrene (l8), a number of mechanisms may be proposed to explain the formation of the products observed.

In view of the mechanistic interest in these reactions, particularly in light of their possible synthetic utility, we decided to venture into other systems.

The simple homologue of 2-chloronorbornene (4), namely 3-chlorobicyclo[3 .2 .13 oct-2-ene (37)a was chosen as the first target of investigation. Compound 2X vas readily available from a two step pro- 20 cedure via the lithium aluminum hydride reduction of exo-3,4-dichloro-

(20) C. W. Jefford, J. Gunsher, D. T. Hill, P. Brun, J. Legros, and B. Waegell, Org. Synthesis, 51, 60 (1971). bicyclo[3 .2 . l]oct-2-ene (52.), which is itself the adduct obtained

from the addition of dichlorocarbene to norbornene (3 8 ).

Compound 37 was found to react sluggishly (7-10 days, 25°) with n-butyllithium when either hexane-ether or ether were employed as solvents. However when the solvent was removed from a 5-fold excess 21 of commercially available n-butyllithium in hexane and replaced by an equal amount of dry tetrahydrofuran, and 3 7 was added, the 22 reaction went to completion in 3 -6 hr, giving a 2.4:1 mixture of

(21) Ventron (Alfa) Inorganics, Inc., 2.2-2.4 M n-butylli thium in hexane; 1.4-2.2 M phenyllithium in 70:30 benzene-ether; 1.9-2.2 M methyllithium in ether.

(22) For a discussion of the stability of organolithrums in tetra hydrofuran see H. Gilman and B. J. Gaj, J. Org. Chem., 22, II65 (1957)* In practice, while substantial reductions in activity are seen at long retention times in tetrahydrofuran with all three organolithiums, in general reactions with the vinyl chlorides mentioned was rapid enough so that this was not a great problem.

3-n-butylbicyclo[3. 2. l]oct-2-ene (4-0 ) and 2-n-butylbicyclo[3• 2. l]oct-

2-ene (4l) in J2fo yield. The mixture proved to be inseparable by a variety of chromatography techniques, including column chromatography on silver nitrate impregnated silica gel, or vapor phase chromatography on a wide range of column types. However the vinyl protons in the

2- and 3-positions of 40^ and 4l (H2 and H3, respectively) were cleanly separated in the nmr spectrum, and the product ratio was determined by the relative integrations of these protons. The structures were established by synthesizing authentic samples of 40_and 4l_by first reacting n-butyllithium with bicyclo[3* 2. l]octan-3-one (4*2) or bicyclo-

[3. 2.1] octan-2-one (44_), and dehydrating the resulting tertiary alcohols

42 & 4o

44 45 4l

with 85# phosphoric acid. Mixing 40 and 4l in the ratio of 2.4:1 gave 16 nxnr and ir spectra identical in all respects to those of the reaction mixture from 37*

Tetrahydrofuran was also the solvent of choice for the reactions of phenyllithium. and methyllithium with £7. Addition of a five-fold excess of 2.2 M phenyllithium in tetrahydrofuran to 37 with reflux for 8 hr gave a 3*3:1 mixture of 3-phenylbicyclo[3.2.l]oct-2~ene (46) and 2-phenylbicyclo[3.2.l]oct-2-ene (47) in JOfi yield. Similarly, stirring 2Z with five equivalents of 2.0 M methyllithium in tetra hydrofuran at 25° for 5 days gave a 60f> yield of an 8.3:1 mixture of

3-methylbicyclo[3.2.1]oct-2-ene (48) and 2-methylbicyclo[3.2.1]oct-2- ene (4ft). In each case the isomers were still inseparable. However, again the hydrogens in the 2- and 3-P°sitions were cleanly separated in the nmr spectrum and product ratios could easily be obtained.

Authentic samples of each compound were obtained (Scheme i) and mixed to provide structure proofs.

Perhaps the first mechanism that comes to mind to provide a rationale for the product mixtures just presented would be a cycloalkyne (elimination-addition) mechanism. Proton abstraction would give the intermediate anion 54, which could then eliminate chloride ion to give bicyclooctyne (55). Such a strained species would be ex- isa, b pected to rapidly add a second equivalent of organolithium from either end of the triple bond to give vinyl anions !?6_and £7, which could be hydrolyzed to give the products mentioned, represented by

III and II. 17

Scheme I

37 46 47 t I

Eh OH OH

50 51 X

42 44

c h 3 OH

OH ai 18

RLi

R © Li '' © L l ® 56l 51

III II

Support for a mechanism of this type in other systems has heen 23 24 gathered by Roberts and by Montgomery. Roberts and coworkers found

(2 3 ) L. K. Montgomery, F. Scardiglia, and J. D. Roberts, J. Amer. Chem. Soc., 8 7, 1917 (1965).

(2b) (a) L. K. Montgomery and L. E. Applegate, ibid., 8 9, 2952 (1 9 6 7); (b) L. K. Montgomery, A. 0. Clouse, A. M. Crelier, and L. E. Applegate, ibid., 8 9, 3^53 (1967)j (c) see also L. K. Montgomery and L. E. Applegate, ibid., 8 9, 53°5 (1967)* .19

that when a 1:1 mixture of l-chlorocyclohexene-2-14C (58) and 1-chloro-

cyclohexene-6-14C (59) was reacted with phenyllithium in ether at

150°, a 285b yield of 1-phenylcyclohexene-X-14C products 6O-65 were

obtained. Degradation of the mixture gave benzoic acid-a'-14C (64)

containing 23 $ of the activity of 58, and 59; and in accord with

this, the cyelohexynes 64 and 65 were postulated ad intermediates.

Similar results were obtained for labeled 1-chlorocyclopentene (66).

58 64 60 61

rh . x y a

65 62 &

Support for intermediates of the type 64_ and 65, in the phenyllithium reactions with deuterium labeled 1-chlorocyclohexene (6?) was provided 24 by Montgomery and Applegate.

In addition, the dehydrohalogenation of aromatic halides to give 25 benzyne and other aryne intermediates is now well established. 20 9a,25,2 6 Cycloalkynes have also "been generated by other methods. m

(25) (a) R. W. Hoffman, ''Dehydrobenzene and Cycloalkynes,*.' ' Academic Ib:ess, New York, 1967; (h) ' 'Chemistry of Acetylenes, ' ' H. G. Viehe, ed., Marcel Dekker, New York, 1969; (c) J. C. Martin and Daniel R. Bloch, J. Amer. Chem. Soc., 93 j 451 (1971); (d) G. Wittig and H. Hega, Ber., 97, 1609 (19657*.

(2 6) (a) G. Wittig and E. R. Wilson, Ber., 9 8, 451 (19 65); (b) G. Wittig, J. Weinlich, and E. R. Wilson, ibid., 9 8, 458 (1 9 6 5); (c) G. Wittig and J. Weinlich, ibid. , §8, 471 (1965); (d) G. Wittig and P. Fritze, Angew. Chem. Intemat. Edit. , 5^ 846 (19 66); (e) For evidence of cyclohexyne as an intermediate in the n-butyllithium reaction of 1-fluorocyclohexene see: G. Wittig and U. Mayer, Ber., 9 6, 329 (1 9 6 3); (f) G. Wittig, Angew. Chem. Intemat. Edit. , 1, 415 (1 9 6 2).

27a-c studies by several groups which appeared after much of the work described here on the bicyclo[3*2. l]oct-2-ene system was completed,

37 and several other bicyclic haloolefins were treated with potassium ST’a-d . 27b _t-butoxide and/or sodium pyrrolidide. Results reported 27a,b,d . 27C implicate bicyclooctyne 55^ (in contrast to an earlier report ) as the major product determining intermediate in most cases, with an exception being the reaction of with potassium t-butoxide in dimethylsulfoxide. In this case (and several others) an allene 27b, c mechanism is implicated.

(27) (a) P. K. Freeman and T. A. Hardy, Tetrahedron Lett., 3 3 17 (1973); Ob) A. T. Bottini and B. Anderson, ibid., 33 21 (1973); (c) P. Monhanakrishnan, S. R. Tayal, R. Vardyanathaswamy, and D. Devaprabhakara, ibid., 2871 (1972); (d) J. J. Brunet, B. Fixari, and P. Caubere, Tetrahedron, 30, 2931 (1974). 2 1

The Reactions of 2-Chlorobicyclo[3.2. l]oct-2-ene (6k).

If bicyclooctyne (55) is the sole intermediate by which 37. reacts with n-butyl, phenyl, and methyl lithiums to form mixtures of 3- and.

2-substituted bicyclooct-2-enes (hence designated as III and II_), it is obvious that the isomeric 2-chlorobicyclo[3.2.l]oct-2-ene (6k) could also react via 55 (and thence 56, and 57) to give product mixtures of III and II. similar to those from £7,. Compound 55, was synthesized by the potassium t-butoxide in t-butanol dehydrochlorination of the gem-dichloride (65.) obtained by treating bicyclo[3. 2. l]octan-2-one

(44) with phosphorus pentachloride.

Cl Cl rci RLi

& St 51

The reactions of 64. were carried out, and the results along with those from J7, are summarized in Table I. The case of methyllithium, where the product ratio changing from 8.3:1 with 37 to 2.5:1 with 6k ? it is evident that some other mechanism is operating,-either exclu sively or in competition with a cycloalkyne mechanism.

Whatever mechanism that might be, the product ratios indicate that it preferentially produces 3-substituted bicyclo[3.2.l]oct-2-enes

(ill) from 37. The differences are smaller for the more reactive and Table I

Summary of Results of the Organolithium Reactions of 37 and 64

Cl RLi RLi

37 III II 6k

from 3X from 64

a R= Yield Ill/ll ratio8, Ill/ll ratio' Yield n-Bu 72 2.4 1.9 63

Hi 70 3-3 2.4 61

Me 60 8.3 2.5 57

Ratios of H I and II were determined by relative integrations of the protons in the 2- and 3- positions, H2 and H3, respectively. 23

presumably less selective n-butyl and phenyl lithiums, but the

Ill/ll ratio is still higher in the reactions of 37. Several com

peting mechanisms are possible.

Abstraction of the allylic proton from 3£ would lead to anion

66 which then could eliminate chloride ion to yield allene 6j.

Allenes are known to undergo nucleophilic attack only at the center carbon of the diene moiety. Such attack by an organolithium would give allylic anion 68, and thence III on hydrolysis. Such a mechanism is impossible for 6b.

RLi -LiCl Cl

A second alternative mechanism is the addition-p-elimination mechanism. Attack at the 3-position of might be easier than attack at the 2-position of 6b. Such a mechanism could be more competitive

* — - C l la H i 2h

ci 6k ii H

TO II

with a cycloalkyne mechanism in the case of 37, thus producing higher

Ill/ll ratios.

Addition of the organolithium in a fashion opposite to that men- 3,4,5a tioned above would produce carbenoids 71 and 72. R migration would then give III and II. respectively.

37 'LiCl

71 III

..LiCl 6h

H II

Still another alternative mechanism is provided by a coupling ea, s mechanism, whereby carbon-carbon and lithium halide bonds are a formed by either a step-wise or concerted mechanism. Again, if the 25

5-position of 37 is more exposed than the 2-position of 6kj perhaps this mechanism could be more competitive in the case of 37. Organo- 6C, sa lithiums are known to form aggregates, which could contribute to stereoselectivity. Colligative properties of methyllithium, phenyllithium, and n-butyllithium in tetrahydrofuran have been measured ssa using differential vapor pressure techniques and through kinetic 28b, c studies. These studies indicate that methyllithium and n-butyllithium exist as solvated tetramers in solution, while phenyllithium exists as solvated dimers in equilibrium with the monomeric species.

Reaction orders, and even relative reactivities, of various organolithiums are concentration dependent for the metallation of triphenyl- 2 8 C 2813 methane and for the addition to 1,1-diphenylethylene. Analysis of this concentration dependence indicates that the dimeric phenyl lithium species is more reactive than the monomer, while the reactive forms of methyllithium and n-butyllithium are less aggregated (presumably monomeric) than the solvated tetramers.

(28) (a) P. West and R. Waack, J. Amer. Chem. Soc., 8 9, ^395 (19&7H (b) R. Waack and M. A. Doran, ibid., 9 1? 2^5& (1 9 6 9H (c) P. West, R. Waack, and J. I. Purmort, ibid. , 92, 840 (1970).

Relative reactivities are also reaction dependent. In the metalla tion reaction of triphenylmethane, the relative reactivities of methyl lithium, phenyllithium, and n-butyllithium were 1: 2.8: 20, while the relative rates for the addition of the three organolithiums to 1,1- 28c diphenylethylene were 1 :0 .3 4 :1900. The metallation of triphenylmethane is of course analogous to the first step of cycloalkyne for mation - the formation of vinyl anions 56_ or 57» While no rate measurements were undertaken in the present study, the relative rates for the metallation of triphenylmethane are in approximate agreement in magnitude and direction with reaction times and temperature necessary for the reactions of the three organolithiums with £7 and 29 6b (and also with other vinyl chlorides to he discussed).

(29) See ref. 19 and references described therein.

It was hoped that quenching the organolithium reactions of 37 and 3§_with deuterium oxide would reveal the presence of anions 56 and 57 and/or 68^ by observing deuterium incorporation into the vinyl and/or allylic positions. However, when the phenyllithium and methyl lithium reactions of 37 and were quenched with deuterium oxide, no deuterium incorporation was observed, even if the reaction was quenched at shorter retention times. This may be due to proton abstraction 27

D 68

22 from the tetrahydrofuran by the anions. However when the faster n-butyllithium reactions were quenched, incorporation was 1 5-20$) from

6k and 40$ from 37, with incorporation being observed in the vinyl positions. Although this offered some support for a cyeloalkyne mechanism, the deuterated analogues of J7, and 6^ were synthesized in order to obtain more definitive evidence about the possible mechanisms.

The Deuterated Chlorobicyclo[3.2.lloet-2-enes.

Scheme II indicates the syntheses of 3-chlorobicyclo[3.2.l]oct-2- ene-2,4,4-d3 (7J\) and 2-chlorobicyelo[3-2.l]oct-2-ene-3-d (T8)- Treat ment of bicyclo[3.2.l]octan-3-one (b2) several times with trifluoroacetic acid-O-d in deuterium oxide gave 79* Chlorination of 7§, with phosphorous pentachloride gave 80, which was dedeuterochlorinated with potassium 1>butoxide in t-butanol to give 77 which was 93$ d3 and

7$ d2 by mass spectral analysis, and ca. 98$ deuterated in the vinyl position by nmr. A similar sequence gave 78. The n-butyl, phenyl, and methyl lithium reactions were carried out, and the results are summarized in Table II. The existence of a substantial deuterium iso tope effect made the use of tetramethylethylenediamine (TMEDA) advisable 2 9 in order to enhance the reactivity of the organolithiums. The effect of TMEDA on n-butyllithium is so dramatic that hexane could now be used Scheme II 29 as a solvent. While yields increases and reaction times decreased, product ratios and deuterium percentages were similar. Effects on phenyl and methyl lithium were less pronounced.

Overall deuterium content was determined by mass spectral analy sis while the percentage of deuterium in the vinyl position was determined by integration of the nmr spectra. In general, the amount of d3 or di products as determined from the mass spectra agreed closely with the amount of vinyl deuterium (percentages of and £_) as determined by nmr.

The n-butyllithium reactions of 77 and T8_ produced mixtures of deuterated products which were 10$ d3 and 15$ d1? respectively.

These figures agreed fairly well with nmr data which indicated the reaction of 77 had retained 18$ deuterium in the vinyl region, while the n-butyllithium reaction of 7§_retained 20$. The fact that these figures agree (and that in fact the nmr figure is slightly larger) indicate that the third or first deuterium is present in the vinyl positions. Thus the d3 and dj. products are indeed 85^ R = nBu, and

86, R = n-Bu. For 8 3 , R = n-Bu, and 84, R = n-Bu, these structures are clear from the nmr spectrum, and it also can be seen that the allylic

C-D stretch region of the ir is intact. Similar conclusions may be drawn for the phenyllithium and methyllithium reactions. For these less reactive organolithiums, larger amounts of vinyl deuterium are retained in the products.

The formation of products 83_ and 84^ from 77, and III and II from

78 strongly support the idea that a cycloalkyne mechanism (87, as Table II 2 9 Organolithium Reactions of 3-Chlorobi eye lo [3 • 2.1] oc t -2- ene - 2,4,4- d3 (77) and 2-Chlorobicyclo[3.2. l]oct-2-ene-3-d (7 8).

1) RLi Cl 2) H20

77 & 84 85

R= % Yield 83/84 ratio ft §5. ft ^3 ft *2 ft di

Cl —— — 93 7 trace n-Bu 77 2.5 18 10 84 6

Hi 46 1-3 23 25 71 4

Me 58 2.7 49 33 62 5 Table II (Continued)

H 1) RLi R

2) H20 R H

78 III II 86

R= 1o Yield Ill/ll ratio8. * 86° % dx % dp’

Cl tm mm — — 88 12 n-Bu 65 2-3 20 15 85

Hi 28 4.8 7 16 84

Me 33 3-5 24 21 79

(a) Product ratios were determined by relative integrations of the vinyl protons of the 3- and 2- substituted products. (b) The percentages of products and 86_was taken to be the % d3 or f> dx (i.e. the percentages of vinyl deuterium), respectively, as determined by nmr. (c) Deuterium percentages were determined by mass spectral analysis.

H Illustrated for 77) is the major mechanism involved in these reactions.

This of course is in spite of the fact that a substantial deuterium isotope effect operates in reactions with the deuterated chlorides.

l)RLi R > 2)H20 D2 d2 H

77 87 &

As mentioned bicyclo[3-2. l]oct-2-yne (55) has previously been postu- 27 lated, and when generated via another route, Wolinsky was able to 30 trap a substituted version of 55, using 1 ,3 -diphenylisobenzofurane.

Trapping attempts in these organolithium reactions were not successful, presumably because the reactive dienes employed were not able to successfully compete with the organolithiums for addition to 55,.

(3 0 ) J. Wolinsky, J. Org. Chem., 26, 704 (1 9 6 1).

The evidence that deuterium is lost from the vinyl positions of

7 7, while protons are not incorporated into allylic positions, ex cludes a cycloallene (8 8) mechanism from consideration. Compound 8g_ is not observed, so this mechanism cannot be involved to explain the

Ill/ll product ratio of 8.3:1 observed in the me thyHithium reaction of 3 7 . The cycloallene mechanism also could not provide an explana tion for formation of d3 and dj. products from 77 and 7 8, respectively. 33

D 77 -#-> 1) RLi 2) H20 R D D 88 §2.

Since the other mechanisms discussed as alternatives to the cyclo-

alkyne mechanism do not involve anions as final intermediates, look

ing at the deuterium percentages does little good in differentiating

among them. However the ratios of 3“ to 2-substituted products pro

vide an additional basis for discussion. For instance, the methyl

lithium reaction of 3X gives a 8-3:1 ratio of and ^ while 77 gives

a 2.5:1 ratio of 83, and 8k. This second ratio appears to be a

'’normal'’ ratio for addition to intermediates 55, or 8j> as illus

trated by the n-butyllithium product ratios from O b XL? or 78. Together with the 2.5:1 product ratio found for the methyllithium

reaction of 6k, this provides additional evidence that the competing

mechanism produces k8_in the reaction of 37_preference to kg.

The carbenoid (9 0) mechanism is rendered unlikely from considera

tion of the fact that methyl migration to the carbenoid center would have to be faster than hydrogen migration in order to explain the

product ratios. Hydrogen migration is known to be favored relative 31 to methyl migration. Thus H migration product k9 would be expected

(31) H. Shechter, personal communication to P. G. Gassman; W. E. Slack, C. G. Moseley, K. A. Gould, and H. Shechter, J. Amer. Chem. Soc., 96, 7596 (197k); See also: J. W. Wilt and W. J. 34

Wagner, J. Org. Chem., 2g? 2788 (1964); A. P. Krapcho and R. Donn, ibid., 30, 641 (196$); See ref. 13 for a discussion of the relative reactivity and selectivity of carbenes and carbenoids.

k8_ 4£ 91

to be formed in preference to 48, if intermediate 90, is involved. In addition, no gl^ was observed.

The addition-P-elimination and coupling mechanisms discussed cannot be differentiated by the data available. To explain product ratios, both mechanisms require that steric factors be decisive enough to allow increased competition with a pycloalkyne mechanism in the case of £7 relative to 64. The bulk of organolithium aggregates has 2 3 been noted. However the addition-f3-elimination mechanism requires 35 addition in a manner opposite to that expected (formation of 69, and

70). Thus it appears that simple coupling may be the competing mechan- 32 ism in these reactions. This may also be the case in the phenyl-

(32) It also appears that methyllithium may react with 2-chloronorbomene (4) to produce 1^ X = CH3 by a coupling mechanism.

lithium and n-butyllithium reactions described, however with competi tion occurring to a smaller' extent with the latter, the product ratios were similar in all cases. 'While trends follow those observed in the methyllithium case, definitive requirements for such a competing mechanism are not evident.

For phenyllithium, retention of vinyl deuterium is only slightly higher than for n-butyllithium in the reactions of 77 and 78. How ever, the ratios of 3 - to 2 -substituted products changes from 3 *3 :1 and 2 . 4: 1 in the phenylli thium reactions of undeuterated 37. 831(1 §}t to 1.3:1 and 4.8:1 in the reactions of 77 and j8. Puzzling results 2 4 a have also been observed by Montgomery and Applegate in their inves tigation of the phenyllithium reaction of l-chlorocyclohexene-2 ,6,6-d3

(9 2). They found that this reaction gave phenyllated products (9 5) in 13 $ yield which retained ca. 1 .9 deuterons in the saturated posi tions, while ca. 0 .8 deuterons per molecule were retained in the olefinic position. Through competition experiments (based on disappear ance of starting material, rather than appearance of product) the authors also found a of ca. 5-3 (at 150°.'). The isotope effect 36 of course indicates that the rate determining step involves C-D bond breaking, presumably as the first step of a cycloalkyne (93) mechanism.

To rationalize retention of vinyl deuterium in light of the isotope effect, the authors postulate an autocatalytic reaction whereby intermediate competes with phenyllithium in the reaction of g2, thus providing essentially a cycloalkyne source for 95*

22 2I 2t

+ 2i --- * + ^

We believe the postulated mechanism to be unlikely for several reasons. First, while phenyllithium is considerably more reactive than methyllithium, we have found that vinyllithium will not react with 2-chloronorbornene (^) even under conditions where methyllithium reacts readily. The phenyl group of £4. certainly would not be ex pected to activate 9b. Thus, it doesn't seem reasonable that §1 should 3 7 compete effectively with 2.5 molar excess of phenyllithium. Further more, if such competition were possible, addition of g4_ to §3 . form 96 might be observed, and indeed this may be a more likely course of reaction for §4^ considering the high reactivity of 9 3 .

No such products were reported, and likewise products of this sort

I>2 Eh Hi II Li . j).

§3 2t 2£ were never observed in the work described here. These authors also 24a studied the phenyllithium reactions of deuterated chlorocyclopentene and chlorocycloheptene, and in these cases results which paralleled those reported here were obtained, providing evidence for cycloalkyne intermediates. The differences observed in the 6-membered ring as compared to the 5- and 7-membered cyclic chlorides were not explained.

The n-Butyllithium Reaction of 2-Chloronorbornene (4). . — - As mentioned in the preceding section, labeling studies by 4 Atkins indicated that 2-chloronorbomene (4) reacted with methyllithium by a mechanism not involving vinyl C-H (or C-D) cleavage, and further, that the reaction proceeded with retention of configuration. Thus 2- chloronorbornene-3-d (97) reacted with methyllithium to give 98, with no loss of deuterium, while optically active (+)-(ls)-2-chloronorbor-

nene (99) gave optically active 100 of absolute configuration indi

cated. These results were interesting in light of results in the

D D

21 2§.

22. ass.

just outlined, where even the methyllithium reactions of labeled

chlorobicyclo[3.2.l]oct-2-enes 77 and 78 resulted in considerable

deuterium loss, and mixtures of 3- and 2-substituted bicyclo[3.2.l]-

oct-2-enes.

Atkins had also found that when was reacted with n-butyllithium

in 1:1 ether-hexane at 25° for 7 days, a mixture of 2-n-butylnortri-

cyclene (1 0 1 ) and 2 -n-butylnorbornene (1 02) was produced in 6l$ yield.

■While a carbenoid (103 ) mechanism seems likely for forming 101, no

evidence was obtained for a mechanism leading to the formation of 1 02.

Candidates for forming 102 are cycloalkyne, addition-P-elimination, 39

n-Bu

-Bu H

101 102 coupling, and also carbenoid mechanisms. Here the carbenoid center of 103 , formed by the addition of n-butyllithium across the double 33 bond of kj could insert into the C-H bond across the ring to give 101, 3 4 or insert into the neighboring C-H bond to give 102. Evidence indi cating that butyl migration is unlikely to be a major factor has been 3 1 presented.

LiCl 101 + 102 •n-Bu H 103

(33) This is a common reaction of this type of bicyclic carbene. For example, see ref. 13, pp 247-250; J. Bredt and W. Holz, J. Prakt. Chem., 203, 133 (1917)'■> A. Angeli, Gazz. Chim. Ital., 24, II, 51771894); J. W. Powell and M. C. Whiting, Tetrahedron, 7? 305 (1959); Clarke, M. C. Whiting, G. Papenmeier, and W. Reusch, J. Org. Chem., 27, 3356 (1 9 6 2); J. H. Hammons, E. K. Probasco, L. A. Sanders, and E. J. Whalen, ibid. , 53 , 4493 (19 68).

(34) See ref. 13, pp 236-240; W. Kirmse and B. von Biilow, Justus Liebigs Ann. Chem., 666, 1 (1 9 6 3). In order to determine which mechanism is responsible for the for

mation of 1 0 2 , and to provide evidence for intermediate 103 as a

precursor to 101, several experiments were carried out. When n-butyl-

lithium in tetrahydrofuran was stirred with 4^ for 2 hr at 25°, and

the reaction was quenched by the addition of deuterium oxide, an 88$

yield of a 1: 6 .1 mixture of 101 and 2-n-butylnorbomene-3 -d (104) was

~ 101 104

obtained. Tricyclic 101 was undeuterated, while 104 was 87$ cLi by mass spectral analysis. When the reaction was run to 95$ completion

and starting material was isolated, it was found that 4_ had been con

verted to 2-chloronorbornene-3-d (97)» which was 93$ di*

The reaction was repeated using 2X £ 1) which was prepared 4 by the method of Atkins. Reaction of 97_with n-butyllithium followed by aqueous work-up gave a 1 6 :1 mixture of 3-n-butylnortricyclene-3-d

(105) and 102 in 88$ yield. Separation by preparative vpc gave 103 41 which was 89% dx while 102 (presumably contaminated with some 1 0 5) was

15% dx- These two pieces of information indicate that tricyclics 105 and

101 are formed by a process not involving either C-D (or C-H) bond cleavage, or a carbanion as a final intermediate. A carbenoid mechanism through intermediates 106 (or 105, Scheme III) fits these criteria.

The formation of bicyclics 102 and 104 have the opposite requirements— vinyl C-D (or C-H) bond cleavage and formation of a vinyl anion 109 as a final intermediate (before quenching). A norbornyne (1 0 8) mechanism fits these requirements. Vinyl deuteron or proton abstraction would give anion 10J, which would form 108 on loss of chloride ion.

Rapid addition of n-butyllithium to 108 would be expected, thus form ing 109 which would be quenched with deuterium oxide to give 104 or water to give 102. As mentioned, §7, which was 93% dj, was isolated when the n-butyllithium reaction of 4_ was quenched with deuterium oxide after the reaction was run to 95% completion. This offers support for

107 as a discrete intermediate, and indicates that loss of chloride to form iiorbornyne (108) is not a fast process. This is not surprising when the strained nature of 108 is considered. The dramatic change in ratios of tricyclic and bicyclic products in the reactions of 4_ and g7

(1 :1 .6 and 16:1 , respectively) indicate that addition of n-butyllithium to the double bond and vinyl deuterium or proton abstraction are the product determining steps of these competing reactions. The reaction of deuterated 9X was not perceptively slower than the reaction of 4, due to the efficient competition of the carbenoid mechanism with that Scheme III involving norbomyne (1 0 8).

Using the assumptions that deuterium has no effect on tricyclic

formation and that the tricyclic products from ^ and §7. arise from

product determining steps for the competing reactions which are both

first order in chloride, a kjjAp 25.6 can be calculated for

bicyclic formation. This is considerably larger than the value of 8.3 35b 35C calculated as a maximum k^/k^ for linear transition states where

C-H (or C-D) bond breaking and : B-H (or :B-D) bond formation are

approximately equally developed. For multicentered reaction, C-H and

C-D bending modes may also be important, and a maximum k^/k^ of 17.2 35b was calculated. Such a multicentered (perhaps involving lithium-

chlorine complexation or proton abstraction by an organolithium 28 aggregate ) could be occurring here. However, multicentered transibr 35C,d tion states have also been used to explain low isotope effects.

(35) (a) G. A. Russell in ''Technique of Organic Chemistry,’' Vol. VIII, Part I, A. Weissberger, ed., Interscience Publishers, Inc., New York, N. Y., 1 9 6 1, p 3^3'» ("b) L. Melander, ' * Isotope Effects on Reaction Rates,’' The Ronald Press Co., New York, N. Y. , i9 6 0, Chap. 2 (c) For a discussion of transition state structure in elimination reactions see: G. Biale, A. J. Parker, I. D. R. Stevens, J. Takahashi, and S. Winstein, J. Amer. Chem. Soc., 9b, 2235 (1972); (d) F. H. Westheimer, Chem. Rev. , 61, 265 (19^2)} (e) V. J. Shiner and M. L. Smith, J. Amer. Chem. Soc., 8 5, 593 (19 61); (f) L. Funderburk and E. S. Lewis, ibid., 8 6, 2531 (1961+).

Tunneling, whereby the wave nature of the proton allows it to pass through a potential barrer (that is in effect proton abstraction) without the system necessarily having enough energy to pass over the 24a barrier, has been used to explain high isotope effects. Shiner

has used tunneling to explain observed isotope effects for proton

removal from l-bromo-2 -phenylpropane larger than can be explained by 35e calculations using ground state, vibrational frequencies. A

kjj/kp of 24 for the proton removalfrom 2-nitropropane has also been 35f rationalized on the basis of tunneling. 26a Unsuccessful attempts have been made to generate cyclobutyne. 26b . , Wittig has succeeded in trapping cyclopentyne (1 1 0 ) as the di-1 ,3 -

diphenylisobenzofuran adduct (1 1 3 ) obtained from the reaction of 111 with n-butyllithium. The rate of decomposition of 112 has also been 2S C studied. Several arynes (e. g. dehydrocyclopentadienyl anion, 25d 26d dehydroindene, and dehydroeoumarane ) have been generated by

other methods and trapped in low yield. Thus it appears that norbornyne (108), a bridged cyclopentyne, may be the most strained cycloalkyne for which literature evidence exists. While the quenching and

labeling studies provide two avenues of evidence for 1 0 8, it seemed that additional evidence would be desirable.

Since 108 was the only symmetrical intermediate involved an any of the possible routes to 102 discussed, it was decided to study the reaction of optically active 2-chloronorbornene (114). According to a modification of the procedure of McDonald and Steppel, 3 6 a (+)-(l£)-/ \ r \ 36b (2S)-norbornyl-2-acetate (11^), which had been obtained by the asym- 37 metric hydroboration method of Brown by treating norbornene with diiso- O

110

Hi Hi

VJ1 46

pinocamphenylborane (prepared from d-gc-pinene and diborane), was

reduced with lithium aluminum hydride to give (+)-(lS)-(2S)-exo-nor-

borneol (12.6), [®]p5 = 1.1 + 0.1° (c, 21.0, CHC13) (Scheme IV). A 38 modified Collin's oxidation of 116 gave (+)-(lS)-norcamphor (llj),

(3 6 ) (a) R. N. McDonald and R. N. Steppel, J. Amer. Chem. Soc., 92, 3664 (19T0)* (b) A sample of 113 was kindly provided by Dr. T. J. Atkins.

(37) H. C. Brown, R. R. Aygangar, and G. Zweifel, J. Amer. Chem. Soc., 8 6, 397 (1964).

(3 8 ) R. Ratcliffe and R. Rodehorst, J. Org. Chem., 35,, 4000 (1 970).

39 = 5*0 +0.1° (c 21.0, CHCI3 ), with a maximum optical purity

of 16%. Treatment of 117 with phosphorous pentachloride gave (+)-(lS)-

2,2-dichloronorbornane (118), [a]p5 = +2.14 +0.1° (c 22.3 j CHCI3 ).

Dehydrochlorination with potassium t-butoxide in t-butanol gave (+)-

(lS)-2-chloronorbornene (114), [

(39) K. Mislow and J. G. Berger, J. Amer. Chem. Soc., 84, 7956 (1 9 6 2); J. A. Berson, R. G. Bergman, J. H. Hammons, and A. W. McRowe, ibid., 8 9, 2581 (1 9 67).

Reaction of 114 with n-butyllithium gave two products, (-)-3-n~

butylnortricyclene (119), [u]^ 5 = -8.1 + 0.1° (c 3*1» CHCI3 ) and 2-n- butylnorbomene (1 0 2 ) (mixture of isomers 121 and 1 2 2 ), [cv]p5 = +2 .0

+ 0.1° (c 3.3, CHC13). The structural correlation for isomers 121 and 47

Scheme IV

OAc OH

H H

115 116

114 118 124

n-Bu

n-Bu H 121 H 119

123

n-Bu 122 bQ

1 2 2 ^ was carried out by first hydrogenating the mixture to give endo-

2-n-butylnorbornane (123), [a] ^ 5 = -0.23 + 0.05° (c 2.5> CHC13) (only one isomer is illustrated). A sample of 123 was also obtained by hydrogenation of 2-butylidenenorbornane (124) which was itself ob tained from the Wittig reaction of n-butyltriphenylphosphine with a portion of the same optically active 117 used to prepare ll4. This

123 had [alp5 = -0.86 +0.1° (c 10.0, CHCI3 ), and thus on the basis of correlation of absolute rotations, the mixture of 1 2 1 and 1 2 2 from the n-butyllithium reaction of 114 is formed with 73 % racemization, presumably through symmetrical intermediate, 108. Together with the quenching and labeling studies, three avenues of evidence for the intermediacy of norbomyne (1 0 8) are presented.

Correlation of the absolute stereochemistry (-)-3-n-butylnor- 39b tricyclene (119) is provided by work of Berson and Bergman. They found that when 3 ~exo-methylnorcamphor (1 2 5) of absolute configuration indicated was converted into the salt of its tosylhydrazone (1 2 6), thermolysis gave (-)-3 -methylnortricyclene (1 2 7), [

-y

H H H

125 126 (-)-127 (95$ ethanol) of ca. 23$ optical purity. Likewise the salt of the tosylhydrazone of the 3 -endo-methylnorcamphor (1 2 8) gave (+) -3 - methylnortricyclene (130), [cv] ^ 3 = +14.7° (95$ ethanol). Thus it

Na'

CH3 128 (+)-13P appears that the n-butyl group has added exo, with the absolute stereo chemistry as indicated, providing stereochemical evidence for the addition-o-elimination (carbenoid) mechanism.

n-Bu n-Bu H H 114 (~)-lQ3 (-)-H9

The Methylated Chlorobicyclo[3.2.lloct-2-enes

‘In the work discussed dealing with the organolithium reactions of the labeled 3 - and 2 -chlorobicyclo[3 .2 .l]oct-2 -enes (7 7 and 7 8), products formed which retained the vinyl deuterium. This provided evi dence that some mechanism (perhaps coupling) could compete with the dominant cycloalkyne mechanism. Putting a methyl group on the double 50

"bond with chlorine would render a cycloalkyne mechanism impossible, and

presumably allow the competing mechanism to assert itself.

With this idea in mind, 3-ehloro-2-methylbicyclo[3.2.l]oet-2-ene

(1 3 1 ) and the isomeric 2 -chloro-3 -methylbieyclo[3 . 2 . l]oct-2 -ene (1 3 2 ) 40 were synthesized as indicated in Scheme V. Allylie alcohol 113 was

(40) (a) R. C. DeSelms and C. M. Combs, J. Org. Chem., 28 , 2206 (1 9 6 3); (b) E. Bergman, ibid.- 28, 2210 (1963); (cTl. Ghosez and P. Laroche, Proc. Chem. Soc., 90 (1 9 6 3 )*

38 oxidized to unsaturated ketone 134; which was hydrogenated to give 4 1 4a a-chloro ketone 135. Treatment of 135 with methylmagnesium iodide

gave 1 5 6, which could be dehydrated to give 131. By the method of 43 Sisti, 137 was converted through its hydroxybromide to a-methyl-

(41) Attempted hydrogenation of 133. gave preferential hydrogenolysis to give 3 -chlorobicyclooctane.

(42) Use of methyllithium was unsatisfactory, presumably due to exporide formation and further reaction.

(43) A. J. Sisti, J. Org. Chem. , 35, 26?0 (1970).

ketone 1 3 8 . Chlorination with phosphorous pentachloride gave 13 9 which was treated with base to give 1 3 2 .

The reactions of 131 and 132 with n-butyl, phenyl, and methyl lithium were carried out. Reaction times necessary were long, and no olefinic products were observed. Surprisingly, mixtures of four 51 Scheme V

535. 134 as.

,CH3

1 5 1

Cl 1 ch3 ch3 H H ax 138 as.

CHs products, with cyclopropyl absorptions in the nmr spectra, were ob served. Preparative scale separation was not possible, but vpc-mass spectral experiments indicated the respective mixtures to be isomers.

Accordingly, the structures represented by 140 and l4l, with a mixture 44 of exo and endo cyclopropyl rings were assigned to the products.

131 140 l4l

(44) Product mixtures from lgl and Ip2 were similar, but not identical for each organolithium.

Stereochemistry is not certain, but was assigned on the basis of pro ducts obtained by reduction of the dichlorocarbene adduct 142 (obtained from a 2.4:1 mixture of 40_ and 4l) to give l4g and l44. Here stereo 53 chemistry is assigned on the basis of assumed exo addition of dichlorocarbene. The spectra of this product mixture were similar to those of

140 and l4l, R = n-Bu, from the n-butyllithium reactions of 131 and

132. However, the cyclopropyl region of the nmr was different, most likely due to l40 and l4l having the major products with cyclopropyl ring endo. These reactions were certainly interesting, so a better system was chosen for detailed study.

Reactions of l-Chloro-2-Alkyicyclohexenes

An obvious candidate as a 1 'blocked'' chloride to repeat the reactions described for 1 3 1 and 1 3 2 was l-chloro-2-methylcyclohexene

(3 A 5). The latter compound cannot be synthesized in a manner which guarantees the position of the double bond if one follows routes similar to those described for 131 or 132. One such route has been 24a described by Montgomery and Applegate. Hiosphorous pentachloride was reacted with 2-methylcyclohexanone (l46) to give l4j, which was treated with base to give a 65:35 mixture of 145 and 148. These isomers were found to not be easily separated, so a subsequent investigation of the phenyllithium reaction of 145 was carried out on 24a the mixture. These authors found that treatment of the mixture with a 5-fold excess of phenyllithium in ether at 150° for 1.3 hr gave 6056 of recovered 145, 23 % of recovered 148, and 17% of a 1 : 1 mixture of 14$) and 150_. These two products are of course formally cycloalkyne products. The fact that no other products are observed was attributed to the fact that a vinyl proton (as in 148) is necessary for reaction, while 145 leads to no phenyllated products, such as 151. 54

CH3 ch3 .CH3

a a Cl Cl

146 147 145 148

orEh a 'Hi c r Hi 151 ISP.

Mils result, of course, is not in accord with the results given for

131 and 1 3 2 , or those to he presented for 145 itself, where here tetrahydrofuran at reflux was used as the solvent.

Preparation of 145 involved dehydrohalogenation of trans-1,2- dichloromethylcyclohexane (152) which was prepared by reacting iodobenzene dichloride with 1-methylcyclohexene (153)« By taking advantage of the fact that the hydrogen at C-2 of 152 is the most acidic hydrogen of the molecule, dehydrohalogenation could be effected with sodium 45 amide in liquid ammonia to give pure 145 in 6 0-705& yield. 55

(45) A variety of other bases were tried, including potassium t- butoxide in various solvents (no reaction or over reaction), exotic and common amines (no reaction), and methoxide and ethoxide (substantial amounts of alkyl ether formation). A strong enough base to abstract a hindered proton to effect a cis-elimination is needed. Thanks are extended to Mr. W. Pike for the idea of this method of synthesizing 145«

155 m . 145

The reactions of 145 were carried out, and again the addition

of N,N,N',N'-tetramethylethylenediamine (TMEDA) shortened reaction

times and improved yields, particularly in the case of n-butyllithium,

where with TMEDA hexane could be used as the reaction solvent. Stirring

145 with 5 equivalents of n-butyllithium in hexane containing 2 .5

equivalents of TMEDA for 29 hr at 25° gave a 78ft yield of a 2.1:1 mixture of 1 -n-butylnorcarane (154) and l-n-butyl-2 -methylcyclohexene

154 2 5 1 (155). These compounds were separated and were identified by com parison with authentic samples. An authentic sample of norcarane lj?4 was synthesized from 1 -n-butylcyclohexene (1 5 6) by methylene transfer 46a reaction using methylene iodide and diethylzine. Olefin 155 was synthesized by dehydration of the alcohol (1 5 7) obtained from the reaction of 2 -methylcyclohexanone (l46) and n-butyllithium.

(46) (a) J. Furukawa, N. Kawabata, and J. Nishimura, Tetrahedron, 24, 55 (1 9 6 8)j (b) J. Nishimura, N. Kawabata, and J. Furukawa, ibid., 25. 2647 (1969).

a Bu an-Bu

O j ' - ' B " OH n-Bu

J5I JSL

In the phenyllithium and methyllithium reactions, only norcaranes were formed. Thus, a 5 hr reflux of 5 equivalents of phenyllithium in tetrahydrofuran containing 2.5 equivalents of TMEDA with 145 gave 57

1-phenylnorcarane (1 5 8) in 84$ yield. The similar reaction with

methyllithium (25 hr reflux, 5*0 equivalents of TMEDA) gave 1-methyl-

norcarane ( in 47$ yield. An authentic sample of 159_ was synthe- . 4ra sized by the method described for the synthesis of 154. Diese 47 three norcaranes have been described in the literature.

m s ass.

(47) (a) For 1 58 and 159 see Y. S. Shabarov, T. P. Surikova, and R. Y. Levina, Zh. Org. Khimii, Vol. 1, No. 10, 1895 (1965); (b) For 1 5 4 and 159 see S. I. Khromov, G. P. Kochnova, 0. I. Guseva, and E. S. Balenkova, Neftek himiya, 6, 8 0 9 (1 9 6 6).

Possible mechanisms for this unprecedented reaction were con sidered and investigated by studying the reactions of l-chloro-2- methyl-d3-cyclohexene (l6o). The results are summarized in Table III.

cd3 cD3 OH O' O C

1 6 1 1 6 2 Table III

Products and Isotope Distribution From the Reactions of l6o with Organoli thiums (RLi)

R= Products Yield $d3 $d2 $dx $dc

CD; 8l 15 aCl

ch3 \ V 42 10b TO 13 T

Hi 68 10b 67 18

164

n-Bu f y ' 0 l4b 62 14 10 \^*"n-Bu 165 72 CD; + CC-bu + Ct;.BU 42 3 8 1 1 9 166 167

(a) Deuterium content was determined by mass spectral analysis, and was confirmed by nmr integration. Deuterium content of the 7- position by nmr analysis were: 165 - 85$; 164 - 79$; 1 6 3 - 80$. (b) This percentage of ''residual'' d3 product(s) may be due to inseparable side-products analogous to 1 6 6 and 1 6 7. 59 The Grignard reagent prepared from iodomethane-d3 "was reacted with cyclohexanone. Alcohol l6l was dehydrated with acid to give 1- methyl-d3-cyclohexene 1 6 2 which was converted to l6o "by the proce dure described for the preparation of 145.

In each case the cyclopropyl absorptions in the nmr spectra of the deuterated norcaranes had virtually disappeared, indicating that the deuterium was in the 7-position. For methyllithium and phenyl lithium, only norcaranes 163 and 164 were isolated. In the case of the n-butyllithium reaction, products 1 6 5, 1 6 6, and 1 6 7 were formed in the ratio of 3:1:1.

From the mass spectral and nmr evidence from the reactions of 160 it seems that the first step leading to the 1-substituted norcaranes 4 8 in allylie deuterium (or proton) abstraction to give intermediate

(48) The synthetic utility of allylic anions formed using n-butyl lithium and TMEDA has recently been explored. R. J. Crawford, W. F. Erman, and C. D. Broaddus, J. Amer. Chem. Soc., 94, 4298 (1972).

l6 8 (Scheme VI). Closure of 168 could be accomplished in two ways..

Path A involves a direct coupling via a 3-membered transition state to give A1’6-norcarene (1 6 9) and lithium chloride. Addition of organolithium would give 1 7 1. which would be hydrolyzed to products.

If this 11 coupling'' is viewed as an intramolecular nucleophilic displacement on an sp2 hybridized center, this method of closure seems less attractive. 6o

Scheme VI

,cd2 o p Li® A GC Cl e x:

1 60 168 2 &

Id© D D B Ck ^ ^ f I A C ’ l Cl

168 1J0 171

R 6l Path B simply involves the 1,3-shift of the electron pair to

give an ^-elimination carbenoid 170. Such a species is analogous to

a number of vinyl carbenes (or carbenoids) found to yield cyclopropenes , v 49 a 49b, c (1 7 2; when generated from organometallic or tosylhydrazone

precursors. An intramolecular reaction of 170 to give 16 9 is of

course analogous to the transformation illustrated for 172a going to

1 7 2b.

CH3 CH3 , N ' I (CH3 ) 2C = C — CH2 — Cl + n-BuLi ---- >- (CH3 )2C= C - CHLi X

1 7 2a

CH3 I I (CH3 )2C = C~CHBr2 + CH3Li

(49) (a) G. L. Closs and L. E. Closs, J. Amer. Chem. Soc. , 8 5, 99 (1 9 6 3) and references to earlier papers therein^ (bj G. L. Closs, L. E. Closs, and W. A. Boll, ibid., 8 3 , 3796 (1 9 6 3H (c) H. Durr, Ber. , 103, 369 (1970).

Since intermediate 16 9 is obviously more strained than a monocyclic cyclopropene this point deserves comment. While A1’6- 62

7,7-dimethylnarcarene (175) (synthesized by photolysis of 3-H-pyra- 50 zole 174) has been identified and found to be stable below -40°,

rearrangements of cv-exo-methylene carbenes to bicyclic cyclopropenes H3C ch3 O x

174 171

is unknown. One example where such a rearrangement does not occur is

illustrated by intermediate 175 generated by the photolysis of 176a in

4° n 0 H

r — q

175 a 175 176b

177 wet benzene. Rather than rearrange to 177 (which would of course be more strained than 173.) > 175 is capturated directly by water to give 51 176b. 63

(50) G. L. (Moss, W. A. Boll, H. Heyn, and V. Dev, J. Amer. Chem. Soc., On, 175 (1 9 7 5 ).

(51) D. H. Morton, E. Lee-Ruff, R. M. Southam, and N. J. Turro, ibid^, k^k-S (1 9 7 0).

A third path, or rather a different way to look at path A, is 8 to imagine the coupling of l68 to 1 6 9 to proceed via diradicals.

Such a process may then be similar to the mentioned photochemical

transformation of 174 to 173. The labeling data, of course, does not differentiate among these possibilities.

The organolithium reactions of l-chloro-2-ethylcyclohexene (178) were also studied. In this case, for reaction to occur by paths analogous to those discussed for 143 and l6 0, a secondary allylic

proton must be abstracted. The n-butyllithium reaction of 178 gave a 3:1:1 mixture of 179, l8 0, and a compound assigned the structure l8l were obtained in 57$ yield. The stereochemistry of 179 is assigned

181

182 on the basis of attack on the face of the intermediate 1 8 2 opposite 52 the methyl group. Olefin l80 -was identified by spectral comparison with an authentic sample obtained by a method similar to that used

(52) L. A. Paquette and S. E. Wilson, J. Org. Chem., 37, 3 8 ^ 9 (1972).

to prepare 15]?. Compound l8l was first thought to be 2-n-butyl-3- ethylcyclohexene (1 8 6) and a structure proof for I8I was attempted following a procedure developed by Ireland for the regiospecific syn thesis of olefins. The addition of lithium diethyl cuprate to l8g gave the enolate l84 which was trapped with diethylphosphorochloridate to give 1 8 5. The reduction of 3B]? with lithium in ethylamine containing t-butanol gave j86 which had an nmr spectrum similar to l8l (parti cularly in the olefinic region), however they were clearly not identical. The structure of 1 8 1 is not certain, but is assigned based on the similarity to l8l.

0 II 0-P(0Et)2 65

(53) R* E. Ireland and G. Pfister, Tetrahedron Lett., 2145 (19&9); R. E. Ireland, D. C. Muchmore, and U. Hengartner, J. Amer. Chem. Soc., §4, 5 0 9 8 (1972).

In contrast to the n-butyllithium reaction, phenyllithium gave

a 30% yield of 1 8 7 while methyllithium gave 24% of I8 9. A 5:1 mixture

187 178 188 1 89

of 1 88 and compounds 1 8 7 and 1 8 6 along with l8 0 could be explained by a coupling mechanism.

However all olefinic products except l8l could likewise be ex- 54 plained by an allene mechanism, as illustrated for the n-butyllithium reaction of 178. Allylic proton abstraction from the ring (also a

(54) A. T. Bottini, R. P. Carson, R. Fitzgerald, and K. A. Frost, II, Tetrahedron, '28 , 4883 (1972).

secondary allylic proton) would give the allylic anion illustrated, which could lose chlorine ion to give 190. Addition of n-butyllithiura would give 191, which would be protonated to give l80. This mechanism could also explain the tri-deuterated products 1 66 and 1 6 7, from the 66

190 191

n-butyllithium reaction of l6 0, however no mechanistic studies were attempted. These reactions of 178 illustrate the fact that a variety of pathways are available to organolithium reagents in their reactions with vinyl chlorides. As discussed, when cycloalkyne mechanisms become energetically unattractive (as was the case with the bicyclo-

[3.2.l]oct-2-ene and bicyclo[2.2. l]heptene chlorides), other mechanisms may compete with the elimination mechanism. In the case of 1 7 8 a cycloalkyne mechanism is impossible, and the mechanism through norcarene 1 8 2 requires the abstraction of a secondary allylic proton, products 1 8 0, 1 8 7, and 1 8 8 could be produced by a competing coupling mechanism.

The n-Butyllithium Reaction of l-Chloro-2-vinylcyclohexene (192).

The title compound (1^2) was prepared by the reaction of triphenyl- phosphonium methylide with 2-chlorocyclohexenecarboxaldehyde (jffi.) • oe - oc 325. 32£ This compound provides an additional example of a case where a cyclo

alkyne mechanism is blocked. To date, studies of reactions of

chlorodienes with organometallic compounds have generally been con- 55 cemed with polymerization reactions. Three exceptions have been

(a) a study of the dehydrochlorination of epimeric l-chloro-4-phenyl- sea butadienes with phenyllithium, (b) a similar methyllithium reaction 56b reported by Corey, and (c) a dehydrochlorination using n-butyl- 56c lithium reported by Kobrich.

(55) B. L. Erusalimskii, et al., Dokl. Akad. Nauk. SSSR, 1 6 9, 114 (1 9 6 6), and references therein; B. L. Erusalimskii, I. G. Krasnosel'skaya, and V. V. Mazurek, Vysokomolekul Soedin., 6, 1294 (1964).

(56) (a) M. Schlosser and V. Landenberger, Ber., 100, 5901 (19^7)» (b) E. J. Corey and R. A. Ruden, Tetrahedron Lett., 1495 (1975 )j (c) G. Kobrich, Angew. Chem. Internat. Edit., 1, 51 (1 9 6 2).

When 1 9 2 was heated at reflux for 20 hr with a five-fold excess

of n-butyllithium in hexane, a' 56% yield of 5-hexylidenecyclohexene

(i22_) was obtained. Diene 195 was identified by comparison with an

authentic sample synthesized by the Wittig reaction of n-hexylidene-' triphenylphosphorane with cyclohexenone (l§4). cc - a This novel reaction may take place "by an initial 1,4-conjugate addition of n-butyllithium on 192, forming carbenoid 195. Hydrogen migration to the carbenoid center would then give Iffi. It should of

192 LiCl

""n-Bu

196

course be noted that 19^ is analogous to carbenoid 170 (Scheme Vi) which was discussed as a possible intermediate in the formation of the norcaranes discussed earlier. However no lj?6 was formed here or in the previous case. F,N,N',N'-Tetramethylethylenediamine was used in the norcarane producing reactions. No support for the un precedented addition-carbenoid mechanism proposed was obtained, but it would not be expected that n-butyllithium in hexane could lead to any sort of an initial dehydrochlorination step. The phenyllithium 69 and methyllithium reactions of 1J2 gave mixtures of products in low- yield under a variety of conditions, and were not farther explored.

Reactions of 2-Chloromethylenenorbornane (1 9 9)»

In the work dealing with the reactions of 3- and 2-chlorobieyclo-

[3*2.l]oct-2-enes (37 and 6k) with organolithiums, evidence was pre sented that the major reaction pathway went through a cycloalkyne intermediate, namely bicyclo[3.2.1]oct-2-yne (5^). It was hoped that intermediate 55. could be generated from a different precursor, yet in the presence of organolithiums, in the hope that Ill/ll product ratios from only 53 could be clearly established and compared with results from and 6k. Wolinsky found that when 1 9 7 was treated with potassium t-butoxide bicyclooctyne 1 9 8 was generated and reacted 5 7 subsequently with jb-but oxide ion, or it could be trapped with 1,3- 30 diphenylisobenzofuran. Other examples of such rearrangements were 58 also studied.

CHBr

1 2 1 ass.

(57) J* Wolinsky, J. Org. Chem., 26, JOk (l96l). TO

(5 8) K. L. Erickson, B. E. Vanderwaart, and J. Wolinsky, Cheat. Common., IO3 1 (1 9 6 8).

In the hope of obtaining an analogous rearrangement (which in- 30,58 volves an a-elimination, and perhaps a free carbene ), 2-chloromethylenenorbornane (lgg) was synthesized as a mixture of epimers 59 by the reaction of chloromethylenetriphenylphosphorane with nor-

(59) D» Seyferth, S. 0. Grim, and T. 0. Reed, J. Amer. Chem. Soc. , 8 3 , 1617 (1961).

m camphor. However when 199, was reacted with n-butyllithium for 0. 5 hr in tetrahydrofuran, an 87% yield of the epimeric 2-pentylidenenorbomanes (200) was obtained. A similar result was obtained for

Hi Hi 199 > + H

200 201 202 71 phenyllithium where a 2:1 mixture of the separable E and Z epimers

(201 and 202, respectively) was obtained in 81$ yield. In the methyllithium in either case, a 3: 1 mixture of 2-ethylidenenorbornane (1 3 7 ) and 3-methylbicyclo[3.1.0]oct-2-ene (48) was obtained in 53% yield.

The presence of 2-methylbicyclo[3.2. l]oct-2-ene (4

199

137 48 spectrum. Structures of all three alkylidenes was proven by comparison with authentic samples obtained by the Wittig reaction of norcamphor with the appropriate triphenylphosphorane. In the case of 1^7 and 4§^ an authentic mixture was prepared.

Because the least reactive organolithium studied, methyllithium, gave some ring expansion attempts were made to change the course of the n-butyllithium reaction by altering the reaction conditions.

Reaction in hexane for 24 hr at 25° or in tetrahydrofuran at -78° for

4 hr, gave 8:1 and 7:1 mixtures of 200 and 40. as determined by nmr.

No 2-n-butylbicyclo[3.2.l]oct-2-ene (4l) could be detected for the same reasons described for 4g. 72

The n-butyllithium reaction with may be imagined to just involve some sort of coupling reaction. An alternative mechanism could be hydrogen abstraction followed by an ^-elimination of lithium chloride to give carbenoid 204. Nucleophilic attack of n-butyllithium followed by quenching with water of the resulting viny Hi thium (205) would give 200. Evidence for such a mechanism was obtained by running the reaction in tetrahydrofuran and quenching with deuterium oxide to give 206, which was 7&f> by mass spectral analysis. Confirmation that the deuterium was incorporated in the vinyl position was provided by nmr.

LiCl

204 205 2 0 6

-7 8°/thf or ,, 2 5° hexane

55 40 41 73

Alpha eliminations of the type leading to 20k are well docu- 9 mented. Nucleophilic attack on carhenoids as illustrated by the formation of 20j> have been observed, but apparently only as a side- 9 reaction occurring in low yield. For example on reaction with n- butyllithium, dichloromethyllithium has been found to yield 2 0 7 in eoa a$> yield, and 2 0 8 has been found to give, on hydrolysis, 20? in Qfo 60b yield. Slightly higher yields have been obtained from the reactions

/ C1 Li - CHC12 + n-BuLi LiCH + LiCl ^n-Bu

o : -

2 0 8 2 0 ?

(60) (a) G. Kobrich and H. R. Merkle, Ber., §£, 1782 (1966); (b) G. Kobrich and W. Goyert, Tetrahedron, 4527 (1 9 6 8).

of organolithiums with vinyl carbenes, 2 1 1 being produced from 2 1 0 . eia in ITp yield on reaction with n-butyllithium, while 9-chloromethyl- 6ib enefluorene (212) gives 19$ of 21p. In the case of the phenyllithium reaction of, 2-chloromethylenecyclohexane (214), 21jj was pro- eic duced in 30-40$ yield.

(6l) (a) G. Kobrich and R. Ansari, Ber., 100, 2011 (1 9 6 7); (b) D. Y. Curtin and W. H. Richardson, J. Amer. Chem. Soc.,4 7 1 9 (1959); (c) H. Gunther and A. A. Bothner-By, Ber., 3112 (1963).

CH-n-Bu CHi 210

CHHi

212

CHC1 ;--- CHFh When the phenyl and methyl lithium reactions of lffg were quenched with deuterium oxide, no deuterium incorporation was noted. In these two cases, alkylidene norbornane formation may be taking place by a coupling mechanism. This could be expected if coupling is faster than proton abstraction for these organolithiums which are of course weaker bases than is n-butyllithium. J

SUMMARY

Labeling studies indicated that the organolithium reactions of

3-chlorobicyclo[3.2.l]oct-2-ene (37) and 2-chlorobicyclo[3.2. l]oct-2-

ene (6b) produced substituted products by way of a bicyclo[3.2.1]oct-2-

yne (3 3 ) intermediate. However, a competing mechanism (perhaps

coupling) was also clearly operating. When a more strained bicyclic

chloride, namely 2-chloronorbomene (^) was studied, labeling impli

cated norbornyne (1 0 8) as an intermediate in the n-butyllithium

reaction of bj leading to the production of 2-n-butylnorbornene (101).

The strain in the double bond of allowed an addition-a-elamination

(carbenoid) mechanism to compete resulting in the formation of 3-n-

butylnortricyclene (102).

When the cycloalkyne mechanism was blocked by synthesizing vinyl

chlorides with a methyl group on the double bond, a novel reaction

giving products containing cyclopropyl rings [e.g. 1-substituted

norcaranes from l-chloro-2-methylcyclohexene (l4j?)1 was observed.

Labeling showed that a primary allylic proton is first removed, and

chloride ion loss (by two possible mechanisms) gives a norcarene

intermediate, which then adds RLi to give, on hydrolysis, 1-substituted

norcaranes. When l-chloro-2-ethylcyelohexene (178) was studied, the

formation of l-substituted-7-methylnorcaranes would require secondary

proton abstraction by the organolithium. When n-butyllithium was

76 77

capable of doing this, both methyllithrum and phenyllithium seem to

react via a coupling mechanism. ■

A scheme involving the 1,4-conjugate addition of n-butyllithium

to l-chloro-2-vinylcyclohexene (l§2) giving 3-hexylidenecyclohexene

(iff?) as a product was presented. The n-butyllithium reaction of 2-

chloromethylenenorbornane (lffff) seems to occur via ^-elimination to

give a carbenoid species (204) which suffers nucleophilic attack to

give 2-pentylidenenorbornane (200) on quenching of the intermediate vinyl anion 20ff.

In conclusion, several unprecedented reactions have been ob

served between vinyl chlorides and organolithium reagents. Mechanisms expanding the scope of possible pathways available for these reactions have been added to the elimination and coupling mechanisms documented in the literature.

( EXPERIMENTAL

Melting points and boiling points are uncorrected. Proton mag netic resonance spe.ctra were on Varian A-60A and A-60 spectrometers.

Infrared spectra were determined on Perkin-Elmer model 137 and 457 instruments. Mass spectra were recorded on an AEI-MS9 spectrometer at an ionization potential of 70 eV, while gc-mass spectra (at 20-70 eV) were recorded on a DuPont 21490 instrument which was coupled with a Perkin-Elmer 990 gas chromatograph. Preparative and analytical vpc work was done on a F&M 810 Chromatograph, equipped with one analy tical and one preparative column, and a thermal conductivity detector.

Optical rotations were obtained on a Perkin-Elmer l4l Polarimeter.

Elemental analyses were performed by the Scandinavian Microanalytical

Laboratory, Herlev, Denmark.

3-Chlorobicyclo[3. 2. l]oct-2-ene (37)• This compound was prepared

according to the procedure of 20 Jefford.

Reaction of 3~Chlorobicyclo[3.2.l]oct-2-ene (%j) with n-Butyllithium.

The solvent was removed from 15.2

ml (3 .5 mmol) of 2.3 M n-butyl-

lithium in hexane on a rotary n-Bu 40 evaporator. The residue was cooled

78 to 0° and 15 ml of dry tetrahydro- 21 furan was added followed by 0.94 n-Bu g (6.6 mmol) of j5£. The solution

was then allowed to warm to 25°

4l and was stirred at 25° for 6 hr.

The mixture was poured onto ice pentane was added, the layers were separated, and the aqueous layer was extracted with three 50-ml portions of pentane. The combined pentane extracts were washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solution was filtered, the sol vent was removed by distillation through a glass helices packed column, and the residue was chromatographed on 100 g of Fisher basic alumina

(pentane) to yield 0 .7 8 g (72$) of a 2.4:1 mixture of 3 -n-butylbicyclo-

[3 .2.l]oct-2-ene (40) and 2 -n-butylbicyclo[3 .2.l]oct-2-ene (4l), bp

72-77° (3.2 mm). These compounds were inseparable but were identified by comparison with a mixture of authentic samples of 40^ and 4l. The nmr (CC14/TMS) of the mixture showed absorptions at T 4.43 (0.7 H, broad d, J = 6.1 Hz), 5-02 (0.3 H, broad m), 7.33-7.93 (4 H, broad m),

7.93-8.92 (12 H, broad m), and 8.92-9 .3 6 (3 H, m).

Bicyclo[3. 2.l]octan-3-one (42). This compound was prepared by the 20 method of Jefford. 3-n-Butylbicyclo[3-2. lloctan-3-ol (43_). A solution of 2.1 g (17 mmol)

of bicyclo[3 .2. l]octan-3 -one (42)

in 20 ml of dry ether was cooled

to 0° and 20 ml (46 mmol) of 2.3 M

n-butyllithium in hexane was slowly OH 62 added. The mixture was allowed

to warm to 25°, stirred for 1 hr, and then poured carefully onto ice. The layers were separated and the aqueous layer was extracted with three 50-ml portions of ether.

The combinedorganic extracts were washed with saturated salt solution and dried over anhydrousmagnesium sulfate. The solution was filtered, the solvents were removed on a rotary evaporator, and the crude alcohol (2,5 g, 89$, contaminated with ca. 5$ of 42) was used without further purification.

(6 2) For a general study of the reaction of alkyllithiums with alde hydes and ketones see: J. D. Buhler, J. Org. Chem., 3 8 , 904 (1973).

The spectral properties of were: nmr (CCI4/TMS): T 7.30-9*32

(broad m, sharp absorptions at T 7-68, 8.47, 8.73 and 9»llH i** (neat)

2.83 , 3 .3 7 , 6.9 2, 8.88, 9.67, 11.06, and 11.65 |j,. Calcd m/e for

Ci2H220: 182.1671. Found: 182.1672. 8 i

3-n-Butylbicyclo[3.2. l]oct-2-ene (40). 'The crude residue 2.5 g (13

mol) from the previous reaction was stirred with 2.0 ml of 85$

phosphoric acid for 1 hr. The solution was poured onto ice and diluted with ether. The layers were separated and the aqueous layer was ex

tracted with three 50-ml portions of ether. The ether extracts were

then washed with saturated sodium carbonate and saturated salt solu tions, and dried over anhydrous magnesium sulfate. The solution was filtered, the ether was removed by distillation and the residue was distilled to yield 1.7 g (77%) of 40, bp 74-76° (4 mm), ng1 = 1.4881, contaminated (nmr) with ca. 5% of an olefinic impurity (presumably

3-butylidenebicyclo[3.2.1]octane). An analytical sample was obtained by preparative vpc on a 4 ” x 1 0 ' 10% SE-30 on 60/80 Chrom W column at 100°.

The spectral properties of 40_ were: nmr (CCI4/TMS) T 4.43 (1H, broad d, J = 6.1 Hz), 7.38-7-94 (4h, broad m), 7.9^-9.38 (15H, broad m, with sharp peaks at T 8.21, 8.48, and 9*09)» ir (neat) 3*40, 6.02,

6.83 , 6.93, 7.26, 8.05, 9.50, and 11.40 p,.

Anal. Calcd for CiaH2o' C, 87.73; H, 12.27.

Found: C, 87.42; H, 12.11.

2-n-Butylbicyclo[3.2. l]octan-2-ol (45). Utilizing the same procedure

outlined for the preparation of

3-n-butylbicyclo[3.2.l]octan-3 -ol

(4 3 ), a solution of 1 .0 g (8 .0

mol) of bicyclo[3 .2 . l]octan-2-one itl 82

(44) (Aldrich Chemical Co.) in 5 ml of dry ether was cooled to 0° and

10 ml (23 mmol) of 2 .3 M n-butyllithium in hexane was added slowly.

The solution was stirred for 1 hr at 25° and worked-up as described

above to give 1.4 g (90fi>) of crude 4^ (contaminated with ca. 5$ of 44)

which was used without further purification.

The spectral properties of 4^_were: nmr (CC14/TMS) T 7.50-9.25

(broad m, 8.6l, 8.82, and 9.0 8); ir (neat) 2.90, 3*40, 6.73> 7.39s

7.46, 8.23 , 8.50, 9.46, 9*93 s and 10.52. Calcd m/e forCi 2H220:

182.1671. Pound: 182.1672.

2-n-Butylbicyclo[3.2.l]oct-2-ene (4l). This compound was prepared

according to the general procedure described for 3 -n-butylbicyclo-

[3 . 2.l]oct-2-ene (4o). Thus, crude 2-exo-n-butylbicyclo[3.2.l]octan-2-

°1 (4jj) (1.3 g5 7.1 mmol) was treated with 1 .0 ml of 85$ phosphoric acid. Work-up and distillation gave 0.82 g (63%) of 41, bp 74-76°

(4 mm), n^5 = 1.4888.

The spectral properties of 4l were: nmr (CCI4/TM 3 ) T 5*05 (1H, broad s), 7.30-9*33 (19H, broad m, sharp peaks at T 7-78, 8.42, and

9.0 8); ir (neat) 3.3*S 6.04, 6.84, 6.95, 7.28, 7.60, 8.0 7, 9*51, H-^3, and 11.97).

Anal. Calcd for C12H20: C, 87.73 ; H, 12.27.

Found: C, 87.60; H, 12.25.

Reaction of 3-Chlorobicyclo[3.2.l]oct-2-ene (37) with Rhenyllithium.

The solvents were removed from 7.0 ml (14 mmol) of 2.0 M phenyllithium in 70:30 benzene-ether on a rotary evaporator. The residue was cooled 83

to 0° and 6 .0 ml of dry tetrahydro-

furan followed by 0.40 g (2 .8 mmol)

of 2X were added- flask was

allowed to warm slowly to reflux

46. and was stirred for 8 hr. The

solution was then poured onto ice,

ether was added, the layers were

separated, and the aqueous layer

was extracted with three 50-ml

47 portions of ether. The ethereal

extracts were washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were removed on a rotary evaporator, and the residue was chromatographed on 50 g of Fisher basic alumina

(pentane) to yield O.3 6 g (70$) of a 3 -3 :1 mixture of 3 -phenylbicyelo-

£3 .2.l]oct-2-ene (46) and 2-phenylbicyclo[3-2-l]oct-2-ene (47), bp

92-94° (O.35 mm). Separation of 46_ and 4£was not possible, however, authentic samples of 46_ and 4£ were prepared and mixed in the ratio

3.3:1- Spectra of this mixture were identical with those of the reaction mixture. The nmr (CC14/TMS) showed absorptions at t 2.74 (5H, s), 3 .6 5 (0.77H, broad d, J = 6.5 Hz), 4.33 (0.23H, broad), 6.98-7-74

(4h, broad m), 7-80-8 .7 7 (6h, broad m, with sharp absorptions at t 8.27 and 8.37). 84

Reaction of 3-Chlorobieyclo[3.2. l]oct-2-ene (37) with Me thylli thium.

The solvent was removed from 16 .6

ml (35 mmol) of 2.1 M methyllithium

on a rotary evaporator. The flask

containing the white, solid

methyllithium was cooled to 0° and

l4 ml of dry tetrahydrofuran was

added followed by 0.94 g (6 .6 mmol)

of 3 X* Ihe mixture was then allowed

to warm to 25° and was magnetically

stirred for 5 days. The solution

was poured carefully onto ice, pentane was added, the layers were separated, and the aqueous layer was extracted with three 50-ml portions of pentane. The combined pen tane extracts were washed with saturated salt solution, and dried over anhydrous magnesium sulfate. The pentane was removed by distilla tion through a glass helices column and the residue was chromatographed on 80 g of Fisher basic alumina (pentane) to yield 0.51 g (60f») of an

8.3:1 mixture of 3-niethylbicyclo[3.2. l]oct-2-ene (48) and 2-methylbicyclo[3.2.l]oct-2-ene (42), bp 42-44° (10 mm). Again, separation of mixture was not successful, but when authentic samples of 48_ and 4^ were synthesized and mixed in an 8.3 :1 ratio, nmr and ir spectra identical to those of the reaction mixture were obtained. The nmr showed absorptions at t 4.48 (0.8h, broad d, J = 6.0 Hz), 5*07 (0.1H,

( 85

"broad m), 7« 43-8.0 0 (4h, broad m), 8.04-8.90 (6h, broad m, -with a

sharp absorption at t 8.53 )-

exo-5-Hienyrbicyclo[3»2-l]octan-5-ol (50). According to the general

procedure described for exo-3 -n-

butylbicyclo[3•2.l]octan-3 -ol

(4^5), 32 ml (70 mmol) of 2.2 M

phenyllithium in 70:30 benzene- 0H ether was added to a solution of 5° 4. 0 g (35 mmol) of 40_ in 20 ml of dry ether. Work-up and removal of solvent on a rotary evaporator gave

6 .0 g of crude 50; contaminated with a considerable amount of biphenyl. 63 This compound has been reported.

(63 ) C. W. Jefford and E. H. Yen, Tetrahedron, 4549 (19^7).

3-Fhenylbicyclo[3.2.l]oct-2-ene (46). According to the general pro cedure described for the dehydration of exo-3 -n-butylbicyclo[3 .2.1]- octan-3 -ol (4j), 6 .0 g (35 mmol) of crude exo- 3 - phenylbi eye lo [3 .2.1] -

(50) was treated with 3*0 ml of 85% phosphoric acid. Work-up and chromatography on 150 g of Fisher basic alumina gave 2.5 g (31%» 63 overall for two steps of known 46, for which only incomplete spectral data had been given in the literature. An analytical sample with n^5 =

1.5802 was obtained by preparative vpc on a i 11 x 10' 10$ SE-30 on 60/80

Chrom W column at l4o°. The spectral properties of 46 were: nmr (CCI4 /TMS) t 2.82 (5H,

m), 3-64 (1H, broad d, J = 7-0 Hz), 7.00-7.75 (4h, broad m), 7.79-8.67

(6h, broad m, sharp peaks at 8.17, 8.27, and 8.3 7 ); ir (neat) 3 *38 ,

5.15, 5.32, 6.25, 6.70, 6.76, 6.92, 9.31, 11-36, 13.30, 13 .60, and

14.46 p,.

Anal. Calcd for C14H16: C, 91.25* H, 8.75.

Found: C, 91-24; H, 8.57-

exo-2-Hienylbicyclo[3-2.l]octan-2-ol (51)♦ The procedure used to

prepare 4^. was employed. Thus,

reacting 1 .2 g (10 mmol) of 44_ in

5 ml of ether with 10 ml (22 mmol)

of 2. 2 M phenyllithium in 70:30

5i benzene-ether followed by work-up

and solvent removal gave 1 .8 g

(89$) of 5JL contaminated with biphenyl, which was used without further

purification.

The spectral properties of 51. were: nmr (CCI4/TMS) t 2.8l (5H,

s), 7.15-9.32 (13H, broad m); ir (neat) 2.87, 3-36, 5-09, 5-29 , 5.50,

6.24, 6.73 , 7-24, 8.44, 9.81, 10.99* 13 .01, 13 *52, 14.31, and 14.80 \l.

Calcd m/e for C14Hia0: 202.1358. Found: 202.1360.

2-Hienylbicyclo[3.2.l]oct-2-ene (4j). This compound was prepared using the procedure described for 40. Thus, crude 1.8 g (8 .9 mmol) of crude exo-2-phenylbicyclo[3 .2. l]octan-2-ol (47) was treated with 0 .5 ml 87

ml of 85$ phosphoric acid. Work-up and column chromatography gave 64 0 .6 0 g of known kj_ contaminated with a small amount of bi

phenyl. An analytical sample, n^4 = 1.5672, was obtained by prepara

tive vpc on a i " x 10' 10$ SE-30 on 60/80 Chrom W column at l40°.

The spectral properties of 4j_were: nmr (CC14/TMS) T 2.80 (5H, m), 4.33 (1H, m). 6.85-7.42( 2H, m), 7.42-7-70 (2H, m), and 7-70-8 .8 2

(6h, broad m with sharp peaks at T .7.75, 7-92, and 8.2 6); ir (neat)

3-39, 6.26, 6.72, 6.93 , 8.67, 9-32, 9-99, 11-40, 13-25, 13 .6 1, and

14.49

Anal. Calcd for C14Hx6: C, 91.25; H, 8.75.

Found: C, 91.23; H, 8.73.

(64) C. W. Jefford, A. Sweeney, and R. Delay, Helv. Chim. Acta, 2214 (1972).

exo-3-Methylbicyclo[3.2.l]octan-3-ol (52). According to the general

procedure described for 3 -n-butyl-

bicyclo[3 .2. l]octan-3 -ol (52) 2 .0 g

CH3 (l6 mmol) of bicyclo[3 . 2. l]octan- 3 -one (42) in 10 ml of ether was OH reacted with 1 7 .0 ml (32 mmol) of

1 .9 M me thylli thium in ether.

Work-up and solvent removal gave 2.2 g (97$) of 4J?. (contaminated with ca. 5$ of 42) which was used without further purification. This com- 65 pound has been previously reported in the literature. 88

(65) W. Kraus and R. Dewald, Justus Liebigs Ann. Chem. , 689^ 21 (1965). A detailed examination of the stereochemistry of 52 and 53 » 311(1 the details of dehydration are presented.

3-Methylbicyclo[3.2.l]oct-2-ene (48). According to the general proce dure described for the preparation of 3 iL> 2 g (15*5 mmol) of crude exo-3 -methylbicyclo[3 .2.l]octan-3 -ol (52) was treated with 2 .0 ml of

85^ phosphoric acid. Work-up and distillation gave 1.5 g (80fo) of M3, 65 bp 153-155 (750 mm) (lit bp 152°) for which no nmr spectral data had been reported. Ihe nmr of 48_ (CC14/TMS) showed absorption at: T

4.42 (XH, broad d, J = 6.0 cps), 7.34 -7.9^ (4h, broad m),7.9^-8.95

(11H, broad m, sharp peak at T 8.48); ir (neat) 3.M}-, 6.10, 6.93 * 7«30j

7.60, 7.80, 8.09, 9.81, 11.44, and 12.19 p.

Anal. Calcd for CsH i4: C, 88.45; H, 11.55*

Found: C, 88.6l; H, 11.46. exo-2-Methylbicyclo[3« 2. l'joctan-2-ol (5 3 ). The preparation of 53. was

accomplished according to the

general procedure described for the

,CH3 preparation of 41. To a solution

OH of 1*0 8 (8 .0 mmol) of bicyclo-

[3 .2.l]octan-2-one (44) in 5 ml of

dry ether was added 20 ml (40 mmol) of 2.0 M methyllithium in ether. Work-up and removal of solvent gave 1 .1 g (98%) of crude, known, £5. (contaminated with ca. 5% of 44) which was used without further purification.

2-Methylbicyclo[3*2.l]oct-2-ene (4 9). Following the procedure used to prepare 3 8 ; 1.1 g (7*9 mmol) of crude was stirred with 1.0 ml of

85$ phosphoric acid. Work-up and distillation gave 0.5 2 g (54%) of 65 49, bp 152-154° (745 mm) (lit 152.5°)• Again, the literature did not provide complete spectral data.

The spectral data for 4g. were: nmr (CCI4/TMS) T 5.00 (1H, broad s), 7*42-9*00 (13H, broad m, sharp peak at T. 8.37)*

Anal. Calcd for C9H3.4: C, 88.45; H, 11.55*

Found: C, 88.42; H, 11.42.

2,2-Dichlorobicyclo[3.2.l]octane (65). To a solution of 2.5 g (20

mmol) of bicyclo[3 .2.l]octan-2-one

(44) in 1 .0 ml of phosphorous

trichloride at 0° was added 4.6 g

(22 mmol) of phosphorous penta-

chloride in small portions over a

period of 1.5 hr. The suspension was then stirred at25° for 20 hr and then poured onto ice. Fentane was added carefully, the layers were separated, and the aqueous phase was extracted with three 5°-ml portions of pentane. The combined extracts were washed with three 50-ml portions of water and 50 ml of saturated salt solution and dried over anhydrous magnesium sulfate. 90

The solution was filtered, the pentane was removed by distillation,

and the somewhat unstable dichloride 6^_ (3 *0 g, 84$) was used without

further purification.

The spectral properties of 6^ were: nmr (CCI4/TMS) T 7.15-8.85

(12H, broad m); ir (CC14 soln) 3*38, 6.90, 10.66, and 11.75 p<*

Calcd m/e: 178.0159* Found: 178.0157*

2-Chlorobicyclo[3. 2.l]oct-2-ene (64). A stirred solution of 4.5 g

(40 mmol) of potassium t-butoxide

in 45 ml of dry dimethylsulfoxide

was cooled to its freezing point

and 3 *0 g (IT mmol) of crude

2,2-dichlorobicyclo[3 * 2.1]octane

(65) was added over a 10 min period.

The solution was allowed to warm to 25°, was stirred for 1 hr, and

poured onto ice. Pentane was added, the layers were separated, and the aqueous phase was extracted with four 50-ml portions of pentane,

three 100-ml portions of water, 100 ml each of saturated solutions of

sodium bicarbonate and sodium chloride, and dried over anhydrous magnesium sulfate. The solution was filtered, the pentane was dis tilled off and the residue was fractionally distilled to yield 1.4 g 27h (57$) of 64, bp 74-75° (20 mm) [lit bp 100-105° (100 mm)]. The 2 7 b , d preparation of this compound has since been reported but no details of the synthesis were given. 91

The spectral properties of 64 -were: nmr (CC14/TMS) t 4.62 (1H, •

m), T.27-8.TT (10H, broad m); ir (CC14 soln) 3.37, 6.08, 6.9 0, 9.65,

9.95, and 10.29 M*.

Anal. Calcd for CaHnCl: C, 67.37; H, 7.77; Cl, 24.86.

Found: C, 67.54; H, 7-77; Cl, 24.54.

Reaction of 2-Chlorobicyclo[3. 2. l]oct-2-ene (64) -with n-Butyllithium.

The solvent was removed from 3.3 ml (7.0 mmol) of 2.0 M n-butyllithium

in hexane on a rotary evaporator. The flask was cooled to 0° and 3-0

ml of tetrahydrofuran was added. After stirring for 5 min, 0.10 g

(0.7 mmol) of 64, in 0 .2 ml of tetrahydrofuran was added, and after warming, the solution was stirred at 25° for 3 hr. The mixture was

then diluted with ether and poured onto ice. The layers were

separated and the aqueous layer was further extracted with two 30 -ml

portions each of ether and pentane. The combined organic extracts were then washed with saturated salt solution and dried over anhy drous magnesium sulfate. The solution was filtered, the solvents were distilled off through a glass helices packed column and the residue was chromatographed on 60 g of Fisher basic alumina (pentane) to yield 72 mg (63%) of a 1.9 :1 mixture of 3 - and 2-n-butylbicyclo-

[3 .2 .1]oct-2-ene (4_0 and 4l, respectively).

Reaction of 2-Chlorobicyclo[3-2. l]oct-2-ene (64) with n-Butyllithium

Followed by Quenching with Deuterium Oxide. This reaction was carried out as described above except that after stirring at 25° for 2 hr the solution was diluted with

ether, cooled to 0°, and 5 ml of

deuterium oxide was added slowly. n-Bu The deuterium oxide layer was lit saturated with sodium chloride the layers were separated and the

organic layer was dried over anhy-

n-Bu drous magnesium sulfate. Filtra

D tion, distillation of the solvents, and chromatography of the residue TL as described gave 6l mg (91%) of a 1.9 :1 mixture of 5- and 2-n-butylbicyclo[3 . 2. l]oct-2-enes (40 and ij-1, respectively). Deuterium incorporation was 14% as determined from the mass spectrum and 20% by nmr, indicating the presence of

14-20% of a mixture of 3 -n-butylbicyclo[5.2. l]oct-2-ene-2-d (lb,

R = n-Bu) and 2-n-butylbicyclo[3.2.l]oct-2-ene-3-d R = n-Bu).

Reaction of 2-Chlorobicyclo[3.2.l]oet-2-ene (64) with Ehenyllithium.

The solvents were removed from 3.1 ml (7.0 mmol) of 2.3 M phenyllithium in 70:30 benzene-ether on a rotary evaporator. The flask was then cooled to 0° and 2.5 ml of tetrahydrofuran was added. After stirring for 5 min, 0 .1 0 g (0.70 mmol) of 64_ in 0.3 ml of tetrahydro furan was added, and the solution was refluxed for 10 hr. The mixture was then diluted with ether and poured onto ice. The layers were separated and the aqueous layer was extracted with two 40-ml portions each of ether and pentane. The combined organic extracts were then

washed with saturated salt solution and dried over anhydrous magnesium

sulfate. The solution was filtered, the solvents were removed on a

rotary evaporator, and the residue was chromatographed on 60 g of

Fisher basic alumina (hexane) to yield 78 mg (6l% ) of 2.4:1 mixture

of 3 - and 2-phenylbicyclo[3 *2. l]oct-2-enes (46_and 4j, respectively).

Reaction of 2-Chlorobicyclo[3. 2.l]oct-2-ene (64) with Fhenyllithium

Followed by Quenching with Deuterium Oxide. This reaction was carried

out as described above except that, after reflux, the reaction solu tion was diluted with dry ether, cooled to 0° and 5 ini of deuterium oxide was added slowly. The deuterium oxide layer was then saturated with sodium chloride and the layers were separated. The organic layer was dried, filtered, solvents were distilled and residue was chroma tographed as described to give a 60$ yield of a 2.4:1 mixture of 3 - and 2-phenylbicyclo[3.2.l]oct-2-enes (46 and 4j ) . No deuterium incor poration was detected by mass spectral or nmr measurements.

Reaction of 2-Chlorobicyclo[3.2.l]oct-2-ene (64) with Methyllithium.

The solvent was removed from 3-5 ml (7*0 mmol) of 2.0 M methyllithium in ether on a rotary evaporator. The flask was cooled to 0° and 3.0 ml of dry tetrahydrofuran was added. After stirring for 5 min, 0.10 g

(0 .7 0 mmol) of 64 in 0 .1 ml of tetrahydrofuran was added, and the solution was refluxed under nitrogen for 18 hr. The solution was diluted with ether and poured slowly onto ice. The layers were separated and the aqueous layer was further extracted with two 25-ml

portions each of ether and pentane. The combined organic phases were

washed with saturated salt solution and dried over anhydrous magnesium

sulfate. The solution was filtered, the solvents were distilled off

through a glass helices packed column and the residue was chromato

graphed on 60 g of Fisher basic alumina (pentane) to yield 48 mg

(57$) of a 2.5 :1 mixture of 3 - and 2-methylbicyclo[3 .2.l]oct-2-enes

(48 and 4^, respectively).

Reaction of 2-Chlorobicyclo[3.2.l]oct-2-ene (64) with Methyllithium

Followed by Quenching with Deuterium Oxide. The reaction was carried out as described above except that after reflux the solution was diluted with ether, cooled to 0°, and 5 nil of deuterium oxide was added. The layers were separated and the organic layer was dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were distilled off, and the residue was chromatographed as described to yield 86fc of a 3 :1 mixture of 3 - and 2 -methylbicyclo-

[3 . 2. l]oct-2-ene (48 and 4^, respectively). No deuterium incorporation was observed by nmr or mass spectral analysis.

Reaction of 3-Chlorobicyclo[3.2.l]oct-2-ene (31) with n-Butyllithium

Followed by Deuterium Oxide Quenching. This reaction was carried out as described above for the n-butyllithium reaction of A solution of 5*5 nil (l4 mmol) of 2.5 M n-butyllithium in tetrahydrofuran containing 0 .2 0 g (24 mmol) of 3X was stirred for 2 hr at 25° under nitrogen.- The solution was diluted with dry ether, cooled to 0°, and

5 ml of deuterium oxide was added slowly. The deuterium oxide layer

was saturated with sodium chloride, the layers were separated, and

the organic layer was dried over anhydrous magnesium sulfate. The

solution was filtered, the solvents were distilled off, and the residue

was chromatographed on 60 g of Fisher basic alumina to yield 0.IT g

( ? W of a 2. 1 mixture of 3 - and 2-n-butylbicyclo[3 .2.l]oct-2-ene

(40 and 4l). Deuterium incorporation was 40$ by mass spectral analysis,

and 37$ by nmr, indicating the presence of ca. 40$ of a mixture of 3 -

n-butylbicyclo[3. 2. l]oct-2-ene-2-d (lkj R = n-Bu) and 2-n-butylbicyclo[3«2.l]oct-2-ene-3-d (73 , R ~ n-Bu).

Reaction of 3-Chlorobieyclo[3.2.l]oct-2-ene (37) with Ehenyllithium

or Methyllithium, Followed by Deuterium Oxide Quenching. When JX was reacted with phenyllithium or methyllithium, as described above, and the reactions were quenched with deuterium oxide, a maximum of

2$ deuterium incorporation could be detected by mass spectral analysis.

Control Reaction of the 3“ and 2-n-Butylbicyclo[3.2.l]oct-2-enes (40 and h3.) with n-Butyllithium Followed by Deuterium Oxide Quenching.

A mixture of iti. was subjected to the reaction conditions des cribed above for the reaction of 3 -chlorobicyclo[3 .2.l]oct-2-ene ($j) with n-butyllithium in tetrahydrofuran followed by deuterium oxide quenching. A maximum of 2$ of deuterium incorporation was observed in the recovered mixture of 40. and as determined by mass spectral analysis. Bicyclo[3.2. l]octan-3-one-2,2,4,4-d4 (72)* According to the general 66 procedure of F a m u m and Mehta,

6.6 g (53 mmol) of bieyclo[3 .2 .1]-

octan-3 -one (42) in a mixture of

6 .0 g (53 mmol) of trifluoro

acetic acid-O-d (prepared by the 22. addition of deuterium oxide to

trifluoroacetic anhydride) and 15.5 g (0*77 mol) of deuterium oxide

was heated in a sealed Carius tube at 155° for 18 hr. The mixture

was diluted with pentane and was neutralized by the careful addition

of anhydrous sodium carbonate. Hie layers were separated and the

aqueous layer was extracted with three 60-ml portions of pentane. The

combined pentane extracts were then washed with 5 ml of deuterium

oxide ana dried over anhydrous magnesium sulfate. The so3.ution was

filtered, the pentane was distilled off, and the above procedure was

repeated three times. At this point the residue was sublimed at J0°

(15 mm) to give 5*6 g (83$) of 72* mp 135-*137°, which was 89$ d4, 10$> d3, 1$ d2, with a trace of d0 by mass spectral analysis; nmr (CC14/TMS): most of the peak at T 7 .8 2 due to protons in the 2- and 4-positions has disappeared, T 7.50 (2H, m), 8 .10-8.65 (6h, broad m); ir (CC14

soln) 3.41, 3*48, 4.52, 4.68 , 4.76, 5.86, 6.89, 7.48, 7.63 , 7-93, 8.58,

8.76, 8.89, 10.55, and 11.15 M-

(6 6) D. G. F a m u m and G. Mehta, J. Amer. Chem. Soc., 91? 3256 (1969)* 3,3-Dichlorobicyclo[3.2.l]octane-2,2,4,4-d4 (80). This compound was

prepared according to the procedure

described above for the preparation

of 2,2-dichlorobicyclo[3.2.l]-

octane (6%). Thus, 5*5 g (43 mmol)

of bicyclo[3 .2.l]octan-3 -one-2,2 ,- 80 4,4-d4 (75O was reacted with 9 -8 g

(47 mmol) of phosphorous pentachloride in 3 ml of phosphorous penta-

chloride. Work-up as described give 6.7 g (85$) of crude 80 which was used without further purification*, nmr (CC14/TMS) t 7*51 (2H, broad m), 7.90-8.70 (6h, broad m)*, ir (CC14 soln) 3 .3 3 , 3.41, 4.38 , 4.54,

4.74, 6.05, 6.15, 6.90, 7.65, 8.64, 9.12, 9.57, 10.07, 10.50, and

11.06

3-Chlorobicyclo[3.2.l]oct-2-ene-2,4,4-d3 (jj). A solution of potassium

t-butoxide was prepared by reflux-

ing a suspension of 5 -1 g (0.13 mol)

of potassium metal in $0 ml of t-

butanol for 6 hr. To the solution

was added 6 .6 g (36 mmol) of 3 ,3 “ II dichlorobicyclo[3.2. l]octane-

2,2,4,4-d4 (80), and the solution was refluxed for 18 hr. After pour ing onto ice, pentane was carefully added, the layers were separated, and the aqueous layer was extracted with four 75-ml portions of pentane.

The combined pentane extracts were washed with four 75-ml portions of water and 75 ml of saturated "brine, and dried over anhydrous magnesium sulfate. The solution was filtered, the pentane was distilled off,

and the residue was distilled to give 1 .9 g (31 %) of JJj bp 80-82°

(20 mm), n^5 = 1.4998* Mass spectral analysis indicated that 7J was

93 % d3 and 7% d2 with a trace of dx product, while nmr analysis indi

cated the vinyl 2-position to be ca. 99% deuterated.

Bicyclo[3.2.l]octan-2-one-3,3 -^ 2 (8l). This compound was prepared by

the procedure described above for

the preparation of bicyclo[3 .2.1]-

octan-3-one-2,2,4,4-d4 (7%),

except that the bicyclo[3 . 2. l]-

8l octan-2-one (44) was only treated twice with acid-deuterium oxide mixtures. Thus, 5*5 g (44 mmol) of 44^ was heated with a mixture of

5 .1 ml (44 mmol) of trifluoroacetic acid-0-d and 12 g (0.60 mol) of deuterium oxide in a sealed Carius tube at 155° for 18 hr. The mix ture was worked-up as described, and the process was repeated.

Work-up and sublimation of the residue at J0° (15 mm) gave 4.2 g (l6f>) of 81, mp 120-122°, which was 9&fo d2 and 4% d^ by mass spectral analysis.

2,2-Dichlorobicyclo[3.2.1]octane-3,3 -^ 2 (8 2). This compound was prepared according to the procedure described above for the prepara tion of 2,2-dichlorobicyclo[3.2.l]octane (6^). Thus, 4.0 g (32 mmol) 99

of bicyclo[3«2.1] oc t an-2-one-3-3- d2

(8l) in 3 “I °f phosphorous tri

chloride was reacted with T. 1 g

(34 mmol) of phosphorous penta-

chloride. Work-up as described 82 gave 5*4 g (94$) of crude 8 2, n^1*6

= 1. 5116, which was used in the following reaction without further purification; ir (CC14 soln) 3*38, 4.50, 6.92, 7»71j 9*28, 10.52,

10.74, and 11.42 p,.

2-Chlorobicyclo[3. 2.l]oct-2-ene-3 -d (j8). This compound was prepared

according to the procedure des

cribed for the preparation of 3-

chlorobicyclo[3.2. l]oct-2-ene-

2,4,4-d3 (71). Thus, 5.3 g (30

mmol) of 2,2-dichlorobicyclo[3.2.1]-

octane-3,3-d2 (82) was reacted with

80 mmol of potassium t-butoxide in 80 ml of t-butanol. Work-up and distillation gave 1.7 g (40$) of J8, bp 80-81° (20 mm), n^ = 1.5041.

Mass spectral analysis indicated that J8_ was 88$ d]_ and 12$ d0, while nmr analysis indicated that the 3-position was 92$ deuterated; nmr

(CCI4/TMS) T 4.69 (0. H, m, vinyl H), 7.25-8.85 (10H, broad m); ir

(CCI4 soln) 3-46, 6.12, 6.9 0, 7-50, 7-72, 8.02, 8.88, 9-85, 10.49, and U . 59 1 0 0

Reaction of 3-Chlorobicyclo[3.2. l]oct-2-ene-2,4,4-d3 (JT) with n-

Butyllithium. To a solution of 2.9 nil (7.0 mmol) of 2.4 M n-butyl-

lithium in hexane were sequen

tially added 0.4l g (3 .5 mmol) of

N, N, N', N' - te trame thylethylene-

diamine and 0 .2 0 g (1 .4 mmol) of

83 R = n-Bu IX* ® ie solution was then warmed

to reflux, stirred for 0 .5 hr, and

then cooled and poured onto ice.

Cl Pentane was added, the layers were separated, and the aqueous layer

was extracted with three 25-ml 84, R = n-Bu portions of pentane. The combined

organic extracts were then washed

with two 40-ml portions of water

and 40 ml of saturated salt solu

tion, and dried over anhydrous n-Bu D2 magnesium sulfate. The solution

8 5, r = n-Bu was filtered, the solvent removed by

distillation, and the residue was chromatographed on 50 g of Fisher basic alumina (pentane) to yield 0.18

6 (77$) of a 2.5:1 mixture of 3 -n-butylbicyclo[3 .2. l]oet-2-ene-4,4-d2

(8ji, R = n-Bu) and 2-n-butylbicyclo[3. 2. l]oct-2-ene-4,4-d2 (84, R = n-Bu), containing (18$) 3-n-butylbicyclo[3.2.l]oct-2-ene-2,4,4-d3 (8 5, 1 0 1

R = n-Bu). Mass spectral analysis showed the mixture to he 10$ d3,

84$ &2> with a trace of d0 compound, while nmr indicated the mixture to he 18$ deuterated on the vinyl carhons (and thus contain

18$ of §5j> R = n-Bu by nmr analysis).

The nmr of the butylated mixture was similar to that of the undeuterated 2.3:1 mixture of 3- and 2-n-butylbicyclo[3.2.l]oct-2-ene

(hO and 4l), except that the allylic proton absorption at t 7 . 60 is absent (The protons at 4-position overlap with the bridgehead proton absorption at T J.77*) and the vinyl proton absorptions were sharpened because coupling (adjacent and allylic) with the protons in the im position was eliminated in the deuterated compounds. The ir (neat) showed absorptions at 3*31> 5*42, 3*49* 4.48 (weak), 4.63, 4.82,

6.82, 7.27, 7.68, 8.51, 9.40, 10.80, and 11.20 p,.

Reaction of 2-Chloro-3-deuteriobicyclo[3«2.l]oct-2-ene (78) with n-

Butyllithium. This reaction was carried out exactly as described

above for the n-butyllithium

reaction of JJ. Thus 0.20 g (1.4 Bu mmol) of j8_ was reacted with 2.9 ml D (7 .0 mmol) of n-butyllithium 86, R = n-Bu containing 0.4l g (3 .5 mmol) of

N, N, N', N' - te trame thyle thylene- diamine. Column chromatography gave 0.15 g (65$) of a 2.3:1 mixture of 2.3:1 mixture of 3-n-*tmtylbicyclo[3.2. l]oct-2-ene (4o) and 2-n- butylbicyclo[3.2.l]oct-2-ene (4l) containing 2-n-butyl-3-deuterio- 1 0 2 bicyclo[3>2.l]oct-2-ene (86, R = n-Bu). Mass spectral analysis indi cated the mixture to he 15^ di, while nmr indicated the presence of 205& vinyl deuterium. The spectral properties were almost identical with those observed for the totally undeuterated 3 - and 2-n-butylbicyclo[3 .2.1]oct-2-enes (40, and ^ijL) except that the vinyl region integrated for slightly less than one proton, and a slight C-D stretch could be seen in the ir (CCI4) at 4.47 p..

Reaction of 3-Chlorobicyclo[3«2. l3oct“2-ene-2,4,4-d3 (77) with Hienyl- lithium. The solvents were removed from 3*2 ml (7*0 mmol) of 2.2 M

phenyllithium in 70:30 benzene-

ether on a rotary evaporator and

3 .0 ml of dry tetrahydrofuran was

added. Next 0.80 g (7.0 mmol) of

83, R = Hi N, N,N' ,N'-tetramethylethylene-

diamine and 0 .2 0 g (1.4 mmol) of

77 were added sequentially, and

Hi the solution was refluxed under

H argon for 6 hr. The mixture was

84, R = Hi poured onto ice, ether was added the layers were separated and the

aqueous layer was extracted with

three 25-ml portions of ether. The

combined ether extracts were washed

D2 with 40 ml each of water and

82, R = Hi saturated salt solution, and dried 105

over anhydrous magnesium sulfate. The solution was filtered, the ether was distilled off, and the residue was chromatographed on 50 g

of Fisher basic alumina to yield 0.12 g (46$) of a 1.5:1 mixture of

5-phenylbicyclo[5.2.l]oct-2-ene-4,4-d2 (85^ R = Hi) and 2-phenylbicyclo[5.2.l]oct-2-ene-4,4-d2 (84;, R = Hi) containing 25$ of 5- phenylbicyclo[3.2.l]oct-2-ene-2,4,4-d3 (&L> R = Eh). The mixture was 25$ d3, 71$ d2, 4$ dx, with a trace of d0 by mass spectral analysis, while nmr indicated the presence of 25$ vinyl deuterium.

The nmr of the mixture was similar to that of a mixture of 5” and 2-phenylbicyclo[5»2.l]oct-2-ene (46 and bj), except that the absorption of the vinyl protons was sharpened due to the presence of the deuteriums in the 4-position, while the allylic hydrogen absorp tions of 46 and bj at T 7-50 was absent. The ir (neat) showed absorp tions at 5*24, 5.27, 5.30 , 5.42, 5.1#, 4.45, 4.62, 4.80, 5.16, 5-35,

5.58, 6.27, 6.70, 6.91, 7.68, 9.37, 10.50, 10.80, 15.40, and 14.50 n.

Reaction of 2-Chloro-3-deuteriobicyclo[3«2.l]oct-2-ene (78) with

Phenyllithium. This reaction was run under conditions identical to

those described above. The reac

tion of 0.20 g (1.4 mmol) of j8_

with phenyllithium, after work-up

and column chromatography gave

86, R = Hi 71 mg (28$) of a 4.8:1 mixture of

5-phenylbicyclo[5- 2. l]oct-2-ene * (46) and 2-phenylbicyclo[5.2.l]oct-2-ene (4j) containing 7$ of 2- pheny 1-3-deuteri obi cyclo[3«2.l]oct-2-ene (86, R = Hi). Mass spectral

analysis indicated that the mixture was 16$ d1} while nmr indicated

the presence of fjo vinyl deuterium. Except for a decrease in the

integral of the vinyl region of the nmr, and the presence of a weak

peak at 4.4-7 the spectra were almost identical to those of a mixture of 46_ and 4j_ not containing 86^ (R = Eh).

Reaction of 3-Chlorobicyclo[3. 2.l]oct-2-ene-2,4,4-d3 (7j) with Methyl-

lithium. The solvent was removed from 3*5 ini (7-0 mmol) of 2.0 M

methyllithium in ether on a rotary

evaporator and replaced by 3*5 ml

of dry tetrahydrofuran. Next

D2 0 .8 1 g (7 .0 mmol) of NjNjN'jN'-

83 , R = Me tetramethylethylenediamine and

0 .2 0 g (1.4 mmol) of 77 were added

sequentially, and the solution was

heated at reflux under argon. After

Da 2b hr, an additional 7*0 mmol of 84, R = Me methyllithium in tetrahydrofuran

was added, and heating at reflux

was continued for an additional 28

hr. The solution was then poured

onto ice, pentane was added, the

layers were separated, and the D2 aqueous layer was extracted with 8 5, R = Me 105

three 25-ml portions of pentane. The combined pentane extracts were washed with two 40-ml portions of water and 40 ml of saturated salt solution, and dried over anhydrous magnesium sulfate. The solution was filtered, the pentane distilled off and the residue was chromato graphed on 50 g of Fisher basic alumina (pentane) to yield 0.10 g

(58$) of a 2.7 :1 mixture of 3 _:roethyTbicyclo[3 .2. l]oct-2-ene-4,4-d2

(83 , R = Me) and 2-methylbicyclo[3*2.l]oct-2-ene-4,4-d2 (84^ R = Me) containing 49$ of 3-methylbicyclo[3.2. l]oct-2-ene-2,4,4-d3 (85, R =

Me). Mass spectral analysis indicated the mixture to be 33$ d3, 62$ d2, 5$ dx with a trace of d0, while nmr indicated the presence of 49$ vinyl deute rium.

The nmr of the mixture was similar to that of a mixture of 3 - and 2-methylbicyclo[3 .2.l]oct-2-ene (48 and 49), except that the deuterium in the 4-position caused a sharpening of the vinyl proton absorptions and of course caused a disappearance of the allylic proton absorption at T 'J. 82, which overlaps with the bridgehead absorptions at T 7*67. The ir (neat) showed absorptions at 3*3°* 3-42, 3*48,

4.45, 4.63, 4.81, 6.9 1, 7.26, 7 .6 6 (d), 9.3 8 , 11.16, and 11.48 p,.

Reaction of 2-Chloro-3-deuteriobicyclo[3.2.l]oct-2-ene (78) with

Methyllithium. This reaction was carried out as described above. A

0 .2 0 g sample of j8 on reaction,

work-up, and chromatography gave

56 mg (33 $) of a 3 *5 :1 mixture

of 3 -niethylbicyclo[3 .2. l]oct-2-ene 86, R = Me (48) and 2-methylbicyclo[3 .2.1]- oct-2-ene (h%) containing 24$ of 2-methyl-3 -deuteriobicyclo[3 .2.1]-

oct-2-ene (86, R = Me). Mass spectral analysis indicated the mixture

to "be 21$ dx, while nmr indicated the vinyl positions to he 24$ dx*

The nmr and ir spectra of the mixture were similar to those of a mixture of 48^ and 4§_ containing no 8

~~Reaction of 2-Chloronorbomene (h) with n-Butyllithium Followed by~~

~~Deuterium Oxide Quenching. The solvent was removed from 7*6 ml (l6~~

~~mmol) of 2.1 M n-butyllithium in~~

~~hexane on a rotary evaporator.~~

~~The flask was cooled to 0°, and~~

~~6 .0 ml of dry tetrahydrofuran was~~

~~added. The solution was stirred~~

~~for 5 min and 0 ,2 0 g (1 .6 mmol) of~~

~~4^ in 0 .5 ml of tetrahydrofuran was~~

~~added. The solution was allowed to~~

~~warm to 25° and was stirred for 2~~

~~hr, at which time only ca. 5$ of~~

~~starting chloride remained. The~~

solution was then cooled to 0°, diluted with ether and 5 ml of deuterium oxide was added. The deuterium oxide layer was then saturated with sodium chloride, the layers were allowed to separate and the organic phase was dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were 107

~~distilled off, and the residue -was chromatographed on 60 g of Fisher~~

~~"basic alumina to yield 228 mg (88%) of a 1:1 .6 mixture of 2-n-butylnortricyclene (101) and 2-n-butylnorbornene-3-di (104) in the ratio~~

~~of 1:1 .6 (as determined by vpc) contaminated -with ca. 5% of 2 -chloronorbornene-3-di (gT). Preparative vpc on a x 12* 10% FFAP on~~

~~60/80 Chrom W column at 90° (with 104 eluting before 101) gave pure~~

~~samples of 101, 104, and with 101 being 0% d]., 104 87% c^, and 97~~

~~93% d]_ as determined by mass spectral analysis. The spectral proper~~

~~ties of 101 and 9J_ were identical to those of authentic samples, while the spectral properties of 104 were: nmr (CCI4/TMS) T 4.57~~

~~(0.1H, broad s), 7.17-7*58 (2H, m), 7*74-9.53 (15H, complex m); ir~~

~~(CC14 soln) 3*32, 3*44, 4 .3 6 (C-D stretch), 6.24, 6.82, 7.29, 7*73,~~

~~7.86, 8.03 , 8.9 6, 11.52 n.~~

~~2-Chloronorbomene-3-d (§7). This compound was prepared by the 4 procedure of Atkins. Cl~~

~~D 21~~

~~Reaction of 2-Chloronorbornene-3-d (97) with n-Butyllithium. The~~

~~solvent was removed from 11 ml~~

~~(23 mmol) of 2.1 M n-butyllithium~~

~~in hexane on a rotary evaporator. n-Bu D Hie flask was cooled, nitrogen was~~

~~i22. bled into the system, and 9*° ml 108~~

~~of tetrahydrofuran was added. The~~

~~mixture was stirred at 0° for 5~~

~~min and 0.3 g (2.3 mmol) of 97~~

~~0 .3 ml of tetrahydrofuran was H 202 added. The solution was allowed~~

~~to warm slowly with cooling to moderate the slightly exothermic reaction, and was then stirred for~~

~~1.5 hr at 25°. The solution was poured carefully onto ice, diluted with ether and the layers were separated. The aqueous layer was extracted with three 25-ml portions of ether and 25 ml of pentane.~~

The combined organic extracts were washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were distilled off, and the residue was chromatographed on

~~60 g of Fisher basic alumina (pentane) to yield 309 mg (88$) of a~~

~~16:1 mixture (as determined by vpc) of 3 -n-butylnortricyclene-3 -d1~~

~~(IO5) and 2-n-butylnorbomene (102). Preparative vpc on a x 12'~~

~~10$ FFAP on 60/80 Chrom W column at 85° gave pure samples of 10J5_ and~~

101. Compound 105 was shown to be 89$ dj, while 101 was 15$ dj, by mass spectral analysis. The spectral properties of 102 were identical with those of an authentic sample while those of 105 were: nmr (CCI4/TMS) t 8.33 (IH, broad s), 8.42-9 .3 8 (l6H, complex m, sharp absorbances at

~~8.80 and 9-09)-, ir (CC14 soln) 3-24, 3-39, 3-49, 4.70 (C-D stretch),~~

~~6.84, 7.3 0 , 7-74, 8.04, 10.63 , 11.60, and 12.05 n; ^ 3 .6 = 1.4650. 109 Control Reaction of 2-n-Butylnorbornene (102) with n-Butyllithium~~

~~Followed by Deuterium Oxide Quenching. A 100 mg sample of 102 was subjected to the reaction conditions described for the reaction of~~

2-chloronorbornene (4) with n-butyllithium followed by deuterium oxide quenching. Work-up and chromatography as described gave 90 mg (90$) of recovered 102 which showed no deuterium incorporation by mass spectral analysis.

~~(+)-(ls)-2-Chloronorbornene (lift-). This compound was prepared from~~

~~optically active norcamphor (117)~~

~~by a modification of the procedure 36b of McDonald and Steppel. Thus,~~

~~(+)-(IS)-(2S)-norbornyl-2-acetate 36b 114 (1 1?), prepared via the asym~~

~~metric hydroboration method of 37 Brown, utilizing optically active diisopinocampheylborane, was reduced with lithium aluminum hydride to give (+)-(IS )-(2S )-norbomane-~~

2-ol (116), [a]g5 = 1.1 + 0.1° (c 21.0, CHCI3 ). A modified Collin’s 38 0 oxidation of 116 gave (+)-(IS)-norcamphor (117), = +5*0 + 0 .1 39a, b (c 21.0, CHCI3 ), with a maximum optical purity of 18%. Treatment of 117 with phosphorous pentachloride in phosphorous trichloride gave

~~(+)-(lS)-2,2-dichloronorbomane (ll8), D* ]^ 5 = +2.14 + 0.1° (c 22.39~~

CHCI3 ). Dehydrochlorination with potassium t-butoxide in t-butanol gave (+)-(is)-2-chloronorbornene (114), [a]^ 5 = +1 .0 + 0.1° (c k.2, 35 CHCI3 ), of 18$ optical purity based on the calculated purity of 117. 1 1 0

~~Reaction of (+)-(lS)-2-Chloronorbornene (ll4) with n-Butylli thrum.~~

~~The solvent was removed from 17*3~~

~~ml (4l. 5 mmol) of 2.4 M n-butyl~~

~~lithium in hexane on a rotary~~

~~n-Bu evaporator. The residue was JJ cooled to 0° -under argon and 15 11? ml of dry tetrahydrofuran, followed~~

~~by a solution of 1 .1 g (8 .3 mmol)~~

~~of 114 in 2.3 ml of tetrahydro-~~

~~n-Bu furan, was added. The solution~~

~~was stirred for 3 hr at 25° and~~

~~poured onto ice. The layers were~~

~~separated and the aqueous layer was~~

~~extracted with two 50-ml portions~~

~~each of ether and 1 :1 ether-pentane.~~

~~The combined organic extracts were~~

~~washed with saturated salt solution n-Bu 1PP and dried over anhydrous magnesium~~

~~sulfate. The solution was filtered, the solvents were removed by distillation, and the residue was chroma tographed on 150 g of Fisher basic alumina (pentane) to yield 0.79 g~~

~~(64$) of a 1:1.6 mixture of (-)-(2R)-2-n-butylnortricyclene (11?) and~~

~~2-n-butylnorbomene (102), which were separated by preparative vpc on a x 15$ FFAP on 60/80 Chrom P column at 95°, with 102 eluting first. Ill~~

~~Recovered 114 (40 mg) showed [alp = +0.91 + 0.1° (c 3*74, CHCI3 ).~~

~~Compound 102 (optical isomers 121 and 122)> had [a]p5 = +2.0 + 0.1°~~

~~(c 3.3» CHCI3 ). Tricyclic 119 showed [®]p5 = -8*1 + 0.1° (c 3*1j~~

~~CHCI3 ), n^6 = 1.4648. The absolute configuration of 119 was supported 3 9 c by the correlation with data supplied by Berson, in his study of~~

~~the optically active 3-methylnortricyclenes 127. and I3 0 . The assump~~

~~tion was made that both the n-butyl and methyl derivatives of the~~

~~same absolute configuration would have the same sign of rotation,~~

~~since this alkyl substitution contributed the only chiral factor to~~

~~the otherwise symmetrical skeleton.~~

~~Hydrogenation of 2-n-Butylnorbornene (121 and 122) • A mixture of 50~~

~~mg (0.33 mmol) of 121 and 122 in~~

~~4.0 ml of methanol containing 50 mg H of yja palladium on carbon was n-Bu stirred under hydrogen for 5 hr~~

~~ipj; on an atmospheric hydrogenator.~~

~~The mixture was filtered through a~~

Celite pad with pentane (100 ml) washing. The pentane solution was washed with 50 ml each of water and saturated salt solution, and was dried over anhydrous magnesium sulfate. The solution was filtered, the pentane was distilled off, and the residue was molecularly dis tilled to yield 2 5 .6 mg (50$) of 2-endo-n-butylnorbornane (125), [a]p5 =

-0.23 +0.1° (c 2.5, CHCI3 ). The ir and nmr of 123 were identical to 4 those (of completely racemic material) obtained by Atkins. (+)-(l£>)-2-Butylidenenorbornane (124). To a suspension of 6.75 g (17.0

~~mmol) of triphenyl-n-butylphos-~~

~~phonium bromide in 30 ml of dry~~

~~ether at 25° was added 7-3 ml~~

~~(17.5 mmol) of 2.4 M n-butyllithium~~

~~224 In hexane, and the resulting deep~~

~~red solution was stirred under nitrogen for 3*5 hr. The solution was cooled to ca. 10° and a solution of 2 .0 g (1 8 .2 mmol) of optically active norcamphor (117) in~~

10 ml of dry ether was added over 15 min. The suspension was heated at reflux for 28 hr, cooled, filtered through Celite to remove triphenylphosphine oxide, and the filtrate was dried over anhydrous magnesium sulfate. The solution was filtered, the solvent was dis tilled off, and the residue was chromatographed on 150 g of Fisher basic alumina (pentane) to yield 1 .3 1 g (51-4$) of 12^ as a mixture of epimers, n^°* 6 = 1.4740, [a]^ 5 = +21.6 + 0.1° (c 10.6, CHC13 ), whose 4 spectral properties were identical to those reported.

~~(-)- (is)-(2R)-endo-2-n-Butylnorbomane (123J). A mixture of 0. 40 g~~

(2 .6 7 mmol) of (+)-(lS)-2-butylidenenorbornane (124) in 5 ml of methanol containing 50 mg of 3% palladium an carbon was stirred under hydrogen on an atmospheric hydrogenator for 5 hr, with one equivalent of hydrogen being taken up. The mixture was then filtered through a

Celite pad with pentane (100 ml) washing. The pentane solution was washed with 100 ml each of water and saturated salt solution, and dried over anhydrous magnesium sulfate. The solution was filtered, 113 the pentane was distilled off and the residue was molecularly dis tilled at 65-70° (10 mm), to yield 0.27 g (67%) of 12?, ngs = 1.4576,

[ c = -0.86 + 0.1° (c 10.0, CHCI3 ). Hie ir and nmr spectra were identical to those of a previously prepared sample of racemic 4 material, as well as with those obtained from the product of the hydrogenation of 121 and 122.

~~3-Chloro-4-exo-hydroxybicyelo[3. 2.l]oct-2-ene (155). This compound~~

~~was prepared by the method of 40c Ghosez and Laroche in 85$ yield.~~

~~SSL~~

~~40a, c 3-Chlorobicyclo[3.2.l]oct-2-ene-4-one (134). To a mixture of~~

~~211.4 g (0 .8 2 mol) of chromium~~

~~trioxide-pyridine complex in 3 -J&~~

~~of methylenechloride was added a~~

~~solution of 2 2 .8 g (0.l4 mol) of~~

~~3 -chloro-4-exo-hydroxybicyclo-~~

[3 .2.l]oct-2-ene (155) in 250 ml of methylenechloride. The mixture was stirred for 10 min at 25°, and most of the solvent was removed on a rotary evaporator. Ether was added to the residue, the solution was filtered, and the residue was distilled through a Vigreux column to yield 16.4 g (73$) of 1J?4, bp

~~76-78° (0.3 mm). An analytical sample, mp 28-29.5°, was obtained by n 4~~

~~preparative vpc on a 4 " x 15' 15% SE-30 on 60/80 Chrom W column at~~

~~l60°.~~

~~The spectral properties of 1 3 4 were: nmr (CC14/TMS) T 2.79 (1H,~~

~~d, J = 7*5 Hz), 6.76-7.23 (2H, m), 7*64-8.78 (6h, hroad m); ir (neat)~~

~~3-33, 5*86 (d), 6.24, 6.89, 7*53, 9*58, 11.08, and 13.00 jj,.~~

~~Anal. Calcd for CaH9C10: C, 61.355 H, 5*79; Cl, 22.64.~~

Found: C, 61.21; H, 5*85; Cl, 22.39*

~~3-Chlorobicyclo[3*2.l]octan-2-one (135)» A solution of 2.40 g (15*3~~

~~mmol) of 3 “Chlorohicyclo[3 .2.1]-~~

~~oet-3 -ene-2 -one (1^4) in 12 ml of~~

~~absolute methanol with 100 mg of~~

~~5% palladium on carbon was reduced~~

~~ipp on an atmospheric hydrogenator.~~

Uptake of hydrogen was 345 ml (379 ml theoretical) over a periodof 19 hr. The solution was filtered, diluted with ether, and dried over anhydrous magnesium sulfate. The solution was filtered, the solvent was removed on a rotary evaporator, and the residue was distilled to yd eld 1.8 g (73%) of 135, mP 68-70°; nmr (CC14/TMS) t 6.70-8.60 (10H, m), 5*5 (1H, broad triplet, J = 10

Hz); ir (CC14 soln) 3*38 , 5.74, 6.88, 7.76, 9*33, 11*37 n*

Anal. Calcd for CsHnClO: C, 60.57; H, 6.99; Cl, 22.35*

~~Found: C, 60.34; H, 7*08; Cl, 22.30 . 3-Chloro-2-exo-methylbicyclo[3.2.l]octane-2-ol (136). To a solution~~

~~of 3-42 g (22 mmol) of 3 -chloro-~~

~~bicyclo[3 * 2.1]octane-2-one (lpp)~~

~~in 1 0 .0 ml of ether at 0° was~~

~~added 6 0 .0 ml (0.15 mol) of 2 .5 M~~

methylmagnesium iodide in ether. 35i The solution was allowed to warm and was stirred at 25° for 2 hr. The excess Grignard reagent was destroyed by the addition of a saturated ammonium chloride solution, the layers were separated and the aqueous layer was extracted with three 50-ml portions of ether. The combined organic extracts were washed with saturated salt solution and dried over anhydrous sodium sulfate. The solution was filtered and the solvent was removed on a rotary evaporator to yield 2.8l g (73$) of crude Ip6 which was used without further purification. The spectral properties of lp6 were; nmr (CC14/tms) t 7.63-9.00 (15H, broad m, methyl singlet at T 8.70); ir (neat) 2.88, 3 .3 8 , 6.88, 7.29, 8.90, 9.53 , and 11.80 jx.

~~Calcd m/e: 174.0811. Found: 174.08l4.~~

~~3-Chloro-2-methylbicyclo[3. 2. l]octene-2 (l^l). T° a solution of 6.0 g~~

~~(31 mmol) of thionyl chloride in~~

~~4 ml of chloroform was added a .CHq solution of 3 *0 g (2 8 .6 mmol) of Cl 2-exo-methyl-3 -chlorobicyclo-~~

~~3 S 3 L [3 .2.l]octan-2-ol (136) in 15 ml 116~~

~~of pyridine, and the solution was allowed to warm to 25°. The solu~~

~~tion was stirred an additional 10 min, the thionyl chloride was removed~~

~~on a rotary evaporator and the residue was poured onto ice. Die mix~~

~~ture was diluted with ether, the layers were separated, and the~~

~~aqueous layer was extracted with two 50-ml portions each of ether~~

~~and pentane. The combined organic extracts were washed with 100 ml~~

~~of water and saturated salt solution and dried over anhydrous magnesium~~

~~sulfate. The solution was filtered and the solvents were distilled~~

~~off on a steam bath through a glass helices packed column at atmos~~

~~pheric pressure. The residue was chromatographed on 180 g of Fisher basic alumina with hexane to yield 0.8^ g (22$) of 151, bp 73-75°~~

~~(0 .5 mm), whose spectral properties were identical with literature 64 values of l^l prepared via another route.~~

~~2-Ethylidenenorbornane (157)• To 400 ml of dry ether was added 8 5 .9~~

~~g (0.23 mmol) of triphenylethyl- 6T phosphonium bromide followed by CH3 140 ml (0 .2 6 mol) of 1 .9 M n-butyl-~~

~~lithium in hexane. After stirring~~

~~I37 for 4 hr, 2 8 .2 g (0 .2 6 mol) of~~

~~norcamphor in 50 ml of ether was~~

slowly added and the mixture was refluxed for 20 hr. The organic layer was decanted off and the residue was washed thoroughly with ether. Hie combined organic extracts were washed with water, saturated salt solution, and dried over anhydrous magnesium sulfate. The solution was filtered, the solvent was removed by distillation, and the

~~residue was fractionally distilled to yield 20.3 g (72$) of 1^7, bp 68 71-75° (48 mm) [lit bp 72-72.2° (50 mm)].~~

~~(67) H. 0. House and G. H. Rosmusson, J. Org. Chem., 26, 4278 (1961).~~

~~(68) If. A. Belikova, et. al., Zh. Org. Khimii, JL, 506 (1965).~~

~~3-Methylbicyclo[3.2.l]octan-2-one (158). This compound was prepared~~

~~according to the procedure of 40 q Sistii, from 2-ethylidenenor-~~

~~bornane (157)* H~~

~~2,2-Dichloro-3-methylbicyclo[3.2.1]octane (139 ) • To 9*79 B (0.0J1~~

~~mol) of neat 3 -methylbicyclo-~~

~~[3 .2.l]octan-2-one (13 8 ) cooled to~~

~~CI2 o° in an ice bath was added slowly CH3 15.20 g (O.O73 mol) of phosphorous H pentachloride through a piece of~~

Gooch tubing over a period of 1.5 hr. The mixture was then stirred at 25° for 24 hr, poured onto ice, and diluted with 50 ml of pentane. The layers were separated and the aqueous layer was extracted with two 100-ml portions of ether and two 118

100-ml portions of pentane. The combined organic extracts were washed with five 100-ml portions of water and 200 ml of saturated salt solu tion, and dried over anhydrous magnesium sulfate. The solution was then filtered and the solvent was removed under vacuum on a rotary evaporator. The spectral properties of 1^2. were: nmr (CC14/TMS) T

~~7.1-7.7 (llH, m), 8.87 (3H, d, J = 6.5 Hz); ir (neat) 3-39, 6.92,~~

~~7.71? 9-29, 12.68, and 13.68 (J.. This compound was not very stable, and was used immediately in the following reaction without further purification.~~

~~2-Chloro-3-methylhicyclo[3«2. l]octene-2 (132 ). To 60 ml of dimethyl-~~

~~sulfoxide containing 1 5 -7 g (Q. I**-~~

~~mol) of potassium t,-but oxide cooled~~

~~to its freezing point was added~~

~~slowly 1 3 .1 g (0.068 mol) of 2 ,2-~~

~~2^2 dichloro-3-methylbicyclo[3. 2.1]-~~

~~octane (132). The solution was allowed to warm to 25° and was stirred for 1 hr. The solution was then poured onto ice and extracted with five 100-ml portions of pentane.~~

The combined pentane extracts were then washed with four 100-ml por tions of water, 100 ml of saturated salt solution, and dried over anhydrous magnesium sulfate. The solution was filtered and the solvent was distilled through a glass helices packed column on a steam bath.

~~The residue was fractionally distilled to yield 3*°5 g (0.0195 mol)~~

~~29$ of 152, bp 63-66° (4.5 mm). The spectral properties of 132 were: 119~~

~~nmr (CCI4/TNS) t 7.32-8.80 (lOH, m in which was found at 8 .3 6 (3H, s),~~

~~the vinyl methyl group); ir (neat) 3*38* 6.02, 6.91, 8.3 5 , 9.54, and~~

~~11.20 |A.~~

Anal. Calcd for C9H 15C1: C, 69.00; H, 8.55; Cl, 22.59*

~~Found: C, 68.82; H, 8.55; Cl, 22.59~~

~~Reaction of 2-Chloro-3-methylbicyclo[3.2.13oct-2-ene (132 ) with n-~~

~~Butyllithium. This reaction was carried out as described for the~~

~~reaction of n-butyllithium with I3 I. Thus, 0.20 g (1-3 mmol) of 132 was stirred with 5*5 ml (13 mmol) of n-butyllithiura in tetrahydrofuran~~

~~for 6 hr at 25°. Work-up and chromatography gave 0.15 g (68%) of exo- and endo-4- and 2-n-butyltricyclo[4.2.1.02’4]nonanes (l40_ and l4l, R = n-Bu). The spectral properties of the mixture were: nmr~~

~~(CCI4/TMS) t 7*30-9*33 (20H, broad m)., 9.55-9-90 (2H, broad m); ir~~

~~(CC14) 3.48, 6.83 , 7-27, 8.56, 9.80, and 11.60~~

~~Reaction of 3-Chloro-2-methylbicyclo[3.2.l3oct-2-ene (131) with n-~~

~~Butyllithium. The solvent was removed from 3*4 ml (6.4 mmol) of 1.9 M~~

~~n-butyllithium in hexane on a~~

~~rotary evaporator. The residue was~~

~~cooled to 0° and 3 -0 ml of tetra~~

~~hydrofuran and 0 .1 0 g (0.64 mmol)~~

~~140, R = n-Bu of 131 was added sequentially. The~~

~~solution was stirred for 6 hr at 25°~~

~~The solution was then poured onto ice, pentane was added, the layers 120~~

~~were separated, and the aqueous~~

~~n-Bu layer was extracted with three 30 ml portions of pentane. The~~

~~combined pentane extracts were~~

~~l4l, R = n-Bu then washed with saturated salt~~

solution and dried over anhydrous magnesium sulfate. The solution was filtered, the solvent was removed by distillation and the residue was chromatographed on 50 g of Fisher basic alumina to yield 80 mg (70^) of a mixture of four products identified as exo- and endo- 4- and 2-n-butyl tricyclo[4.2 .1.02j4]- nonane (l4o and 141^ R = n-Bu).

~~When the mixture was subjected to vpc-mass spectral analysis, similar cracking patterns were obtained for all four components.~~

This was also true for the other mixtures obtained from the phenyllithium and methyllithium reactions of 151 and 132 . The spectral properties of this mixture were: nmr (CCI4/TMS) t 7.53~9»39 (20H, broad m), 9»57-9*91 (2H, m); ir (CCI4 soln) 3*36, 6.87* 7*27, 8.56,

~~9.78, and 11.64 [j,. endo-4-n-Butyl-3,3 -dichlorotricyclo[4. 2.1.02’4]nonane (142a.) and 2-n-~~

~~Butyl-3,3-dichlorotricyclo[4. 2.1. 02j4]nonane (142b). A 100 ml, three~~

~~necked round-bottomed flask was~~

~~fitted with a condenser, thermo-~~

~~meter, and addition funnel. Sodium n-Bu methoxide (5-4 g, 0 .1 mol) and 4.5 g 142a 121~~

~~(27. 4 mmol) of a 2.3:1 mixture~~

~~of 3- and 2-n-butylbicyclo[3.2.1]-~~

~~oct-2-enes (40^ and 4l, respect~~

~~ively) in 20 ml of olefin-free~~

~~142b pentane were added to the flask.~~

~~Die suspension was cooled to -5°~~

~~in an ice-salt bath and 15.0 g (80 mmol) of trichloroethylacetate was~~

~~added dropwise over a 3 hr period, the temperature of the mixture~~

~~being kept below 0°. Die mixture was stirred below 0° for 4 hr and~~

~~the temperature was allowed to rise slowly to room temperature 69 overnight. The mixture was then poured onto ice, the ice was~~

allowed to melt, the layers were separated, and the aqueous layer was further extracted with four 50-ml portions of ether. The combined organic extracts were washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were distilled off, and the residue was distilled through a

~~Vigreux column to give 4.4 g (66^) of 142a and 142b, bp 120-122°~~

~~(0.9 mm). The spectral properties of the mixture of 142a and 142b were: nmr (CC14/tM3) t 7.29-9*28 (broad relatively sharp signals at~~

~~T 8.12, 8.42, and 9.08; ir (neat) 3*36, 5-70, 6.83 (d), 7-90, 9*38,~~

~~10.48, 11.29, 11.81, 12.81 ijl; nj9*4 = 1.5078. Calcd m/e: 246.0942.~~

~~Found: 246.0945.~~

(69) C. W. Jefford, et.al., Chem. Commun., 310 (1967); Jefford reports exo addition of dichlorocarbene to bicyclo[3.2. l3oct-2- ene and states that the resulting dichloride opens only above 200°. 122 endo-U-n-Butyltricyclo[4.2.1.02’4]nonane (l4j ) and 2-n-Butyltricyclo-

~~[4.2.1.02»4]nonane (l44). To 15 ml of liquid ammonia (distilled~~

~~from sodium) in a 50-ml 3-necked~~

~~flask fitted with a dry-ice-iso-~~

~~propanol condenser and pressure~~

~~equalizing dropping funnel was~~

~~— added 1.04 g (45 mmol) of sodium 145 in small, shiny chunks. After the~~

~~sodium had dissolved, 4.3 g (17~~

~~mmol) of 142 in 15 ml of freshly~~

~~dried glyme was added slowly.~~

~~The solution was then allowed to n-Bu stir at reflux for 3 hr and 1. 75 144 g of ammonium chloride was then~~

added. The mixture was allowed to warm slowly and the ammonia allowed to evaporate overnight. The contents of the flask were diluted with water and ether and the layers were separated. The aqueous layer was extracted with three 50-ml portions of pentane. The combined organic extracts were then washed with saturated salt solution and dried over anhydrous magnesium sulfate.

The solution was filtered, the solvents were distilled off, and the residue was fractionally distilled to yield 1.48 g (4<$) of a 2.9:1 mixture of 143 and 144, bp 73 -75° (0*85 mm) of ca. 98f> purity as determined by vpc, n^4 = 1.4788. Pure samples of 142, and 1*^ were 125

~~obtained by preparative vpc on column C at 85° with 145 eluting first.~~

~~Bie spectral properties of 1kj were: nmr (CC14/TM3) T 7-77 (1H, m),~~

~~7.29-9-53 (19H, broad m), 9-73 (1.4h, s ) , 9-84 (0.60H, J = 2.8 Hz);~~

~~ir (CC14 soln) 3.48, 6.84, 7-29, 9-84, and 11.6 1 n; ng4 = 1.4768.~~

~~Anal. Calcd for C13 H22: C, 87.56; H, 12.44.~~

~~Found: C, 87.55; H, 12.3 8~~

~~The spectral properties of l44 were: nmr (CC14/TMS) T 7.78 (1H, m),~~

~~7« 90-9* 42 (19H, broad m), 9 .6 9 (2H, broad s); ir (CC14 soln) 3*44, 6.82,~~

~~7.27, 9-83, and 11.38 n; ng4 = 1.4805.~~

~~Anal. Calcd for C13 H22: C, 87.56; H, 12.44.~~

~~Found: C, 87.36 ; H, 12.34.~~

~~Reaction of 3-Chloro-2-methylbicyclo[3. 2.l]oct-2-ene (151) -with~~

~~Hienylli thium, The solvent was removed from 2.8 ml (6.4 mmol) of 2.3~~

~~M phenyllithium in 70:30 benzene-~~

~~ether on a rotary evaporator. The~~

~~residue was cooled to 0° and 2.8 ml~~

~~of dry tetrahydrofuran and 0.10 g~~

~~140, R = Ha (0.64 mmol) of 151 was added sequentially. The solution was~~

~~warmed to reflux and stirred under~~

~~nitrogen for 8 hr. The solution~~

~~was poured onto ice, diluted with~~

~~ether, and the layers were separated,~~

~~141, R = Ri The aqueous layer was extracted~~

~~with two 25-ml portions each of 124~~

~~ether and pentane. The combined organic extracts were then washed with saturated salt solution and dried over anhydrous magnesium sul~~

~~fate. The solution was filtered, the solvents were removed on a rotary evaporator and the residue was chromatographed on 50 g of~~

~~Fisher basic alumina to yield 80 mg (63$) of a mixture of four pro ducts which were assigned the structures of exo- and endo-4- and 2-~~

~~phenyltricyclo[4. 2.1.02>4]nonane (l40 and l4l, R = fh) on the basis of spectral properties.~~

~~The spectral properties of the mixture were: nmr (CCLj/TMS) T~~

~~2.93 (5H, s), 7.22-9.03 (llH, broad m), 9*03-9.53 (2H, broad m); ir~~

~~(CC14 soln) 3*35 , 5*09 , 5*21, 5*51, 5*75, 6.21, 6.6 9, 6.8 8, 8.01,~~

8.95 , 9*72, and 11.58 n*

~~Reaction of 2-Chloro-3-methylbicyclo[3.2.l]oct-2-ene (132 ) with~~

~~RienylHithium. This reaction was carried out in the same manner as the reaction of lgl with phenyllithium as described above. Thus,~~

0 .1 0 g (0.64 mmol) of 152 was refluxed for 10 hr with 2 .8 ml (6.4 mmol) of 2.3 M phenylli thium in tetrahydrofuran. Work-up and chroma tography gave 62 mg (49$) of a mixture of compounds assigned the structures of exo- and endo-4- and 2-phenyltricyclo[4.2.1.02>4]nonane

~~(l40 and 141, R = Eh) on the basis of spectral properties, which were very similar to those of a mixture obtained from the phenyllithium reaction of 151.~~

~~The spectral properties of the mixture were: nmr (CC14/TMS) t~~

~~3.42 (5H, s), 7*27-9*06 (11H, broad m), 9.06-9 .5 7 (2H, broad m); ir 125~~

~~(CC14 soln) 5.37, 5-15, 5-34, 5-56, 5.80, 6.23, 6.69, 6.87, 7.27,~~

~~9.71, and 11.59 M"~~

~~Reaction of 3-Chloro-2-methylbicyclo[3.2.l]oct-2-ene (151) with~~

~~Methylli thium. The solvent was removed from 3*5 ml (6.4 mmol) of~~

~~1.9 M methyllithium in ether on a~~

~~rotary evaporator and was replaced~~

~~by 3*0 ml of tetrahydrofuran. The~~

~~chloride 131 (0 .1 0 g, 0.64 mmol)~~

~~was added, and the solution was~~

~~heated at reflux under nitrogen~~

~~for 48 hr. The solution was poured~~

~~onto ice, pentane was added, the~~

~~layers were separated, and the~~

~~aqueous layer was extracted with~~

~~three 40-ml portions of pentane.~~

~~The combined pentane extracts were~~

dried over anhydrous magnesium sul fate. The solution was filtered, the pentane was distilled off, and' the residue was column chromatographed on 50 g of Fisher basic alumina to give 22 mg (25$) of a mixture of four products identified as exo- and endo-4- and 2-methyltricyclo[4.2.1.02»4]nonane (l4o and l4l, R = Me).

~~The spectral properties of the mixture were: nmr (CCI4/TMS) T~~

~~7.50-9 .3 5 (14H, broad m), 9.60-9.95 (2H, m); ir (CC14 soln) 3*35, 6.92,~~

~~7.30, 8.55, and 11.75 ji. 126~~

~~Reaction of 2-Chloro-3-methylbicyclo[3.2. l3oct-2-ene (l?2) with~~

~~Methyllithium. This reaction was carried out by the same procedure~~

~~as described for the reaction of methylli thium with lgl. Thus, 0.20 g~~

~~(1.3 mmol) of 132 was refluxed for 48 hr with 6.0 ml (13 mmol) of 2 .2~~

~~M methyllithium in tetrahydrofuran. Work-up and column chromatography~~

~~gave 62 mg (35$) of a mixture of four products (similar to those~~

~~from the methyllithium reaction of 131 ) which were identified as exo-~~

~~and endo-4— and 2-methyltricyclo[4.2.1.02>4]nonane (l4o and l4l; R =~~

~~Me).~~

~~The spectral properties of the mixture were: nmr (CCI4/TMS) T~~

~~7.20-9.40 (14H, "broad m), 9.65-9.95 (2H, m); ir (neat) 3.40, 6.89,~~

~~7.28, 8.56, 9.82, and 11.76.^.~~

~~trans-l,2-Dichloromethylcyclohexane (152). Nitrogen was bubbled~~

~~through a suspension of 100.3 g (0 .3 6 mol) of iodobenzene dichloride~~

~~in 750 of carbon tetrachloride~~

~~CH3 for 15 Min and 35*0 g (0 .36 mol) L Cl of 1-methylcyclohexene was added. - C l~~

~~H The solution was then brought slowly to reflux, while irradiating a152 (through the Pyrex flask) with a~~

Hanovia 3°620 quartz ultraviolet lamp, with the solution clearing between approximately 60 and 70°. The solution was heated at reflux for 0 .5 hr, cooled in an ice-salt bath and chlorine was bubbled through the solution for 2 hr to regenerate the iodobenzene dichloride. The 127

~~solution was allowed to warm slowly, dry nitrogen was again bubbled~~

~~through the system and the mixture was filtered to remove iodobenzene~~

~~dichloride. The filtrate was washed sequentially with saturated~~

~~sodium chloride solution, and dried over anhydrous magnesium sulfate.~~

~~The solution was filtered, the solvent was distilled off, and the residue was fractionally distilled to yield 42.2 g (70%) of 1^2 , bp TO 103-105° (55 mm).~~

~~(70) For ir data of 152 see: C. Altona, II. J. Hageman, and E. Havinga, Spectrochimica Acta, 2kA, 633 (1968).~~

~~l-Chloro-2-methylcyclohexene (lVj_). A solution of sodium amide in~~

~~liquid ammonia was prepared by the~~

~~addition of 15-5 8 (0»6j mol) of~~

~~sodium to 400 ml of ammonia con-~~

~~taining 0 .2 g of ferric nitrate~~

~~nonahydrate (0 .2 g of sodium was~~

~~first added and air was bubbled through the solution until the blue color dissipated and the black catalyst formed). The solution was stirred for 0 .5 hr and 39*3 8~~

(0.23 mol) of trans-1 ,2-dichloromethylcyclohexane (152) was added dropwise over 0.5 hr. Stirring was continued for 9 hr and 30 ml of ether was then added, followed by 2 7-2 g (0 .5 mol) of solid ammonium chloride (added cautiously in small portions through a piece of Gooch tubing). The ammonia was allowed to boil off overnight, and water was added to the mixture. The layers were separated and the aqueous

~~layer was further extracted with two 125-ml portions of ether and 150 ml of pentane. The combined organic extracts were washed with~~

~~saturated salt solution and dried over anhydrous magnesium sulfate.~~

The solution was filtered, the ether was distilled off and the residue was distilled through a Vigreux column to yield 1T»9 g (58%) of lb-3, 71 bp 79“8l (44 mm) [lit bp 4l-42° (8 mm)] of greater than 99% purity

~~as indicated by vpc, n^4,6 = 1.4831. No olefinic protons could be~~

~~detected by nmr analysis.~~

~~(71) M. Mousseron and R. Jaquier, Bull. Soc. Chim. Fr., 648 (1950).~~

~~The Reaction of l-Chloro-2-Methylcyclohexene (l45) with n-Butyllithium.~~

~~To a solution of 38.3 nil (76.5~~

~~mmol) of 2.0 M n-butyllithium in~~

~~hexane at 0° under argon was added~~

~~4.45 g (58.2 mmol) of N,N,N*,N'- ,-Bu tetramethylethylenediamine, followed~~

~~154 by 2.0 g (15*3 mmol) of 145• The~~

~~solution was stirred at room~~

~~temperature for 29 hr and poured~~

~~carefully onto ice. The layers~~

were separated and the aqueous a^ " n-Bu layer was further extracted with 125. 129 two 50-ml portions each of ether and 1:1 ether-pentane. The combined organic extracts were washed with 100 ml of water, saturated salt solution and dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were distilled off, and the residue was chromatographed on 200 g of Fisher basic alumina (pentane) to yield

~~1 .8 2 g (l&fo) of a 2 :1 mixture of 1-n-butylnorcarane (154) and 1-n- 4Tb butyl-2-methylcyclohexene (155)? bp 88-91° (44 mm) [lit. bp 102.5°~~

(4l mm)]. These compounds were separated by preparative vpc on a 4 " x 15' 15% FFAP on 60/80 Chrom P column at 70°, with 155eluting first, and were identified by spectral comparison with authentic samples.

~~The spectral properties of 154 were; nmr (CC14/TMS) t 7*76-9*56~~

~~(18H, broad m, sharp peaks at 8 .7 6 and 9*ll)> 9*56-9*95 (2H, m); ir~~

~~(CC14 soln) 3.36, 6.85 (d), 8.02, 9.83, and 11.5 8 n; nf5' 2 = 1*4543.~~

~~The spectral properties of 155 were: nmr (CC14/TM3) T 7*85-9*24~~

~~(22H, broad m, sharp peaks at t 8.38 , 8.73 , and 9*°9)s i r (CC14 soln)~~

~~3*40, 6.8 9, 7*24, 8.02, and 11.59 m ng1* 8 = 1.4628.~~

~~Anal. Calcd for Cu H2o: C, 86.76; H, 13.24.~~

~~Found: C, 86.52; H, 13.42.~~

~~46a 1-n-Butylnorcarane (154). Utilizing a literature procedure, 20.0 g~~

(75 mmol) of methylene iodide (Aldrich) was added under argon to a solution of 5 ml (50 mmol) of diethylzinc (Stauffer) and 5*0 g (36 mmol) of 1-n-butylcyclohexene in 20 ml of pentane and the solution was then stirred for 4 hr. Water was carefully added, the layers were separated, and the aqueous layer was further extracted with two 50-ml

~~portions of ether. The aqueous layer was then acidified with~~

~~saturated ammonium chloride solution and extracted with two additional~~

~~50-ml portions of ether. The combined organic extracts were washed~~

~~with saturated salt solution and dried over anhydrous magnesium sul~~

~~fate. The solution was filtered, the solvents were removed by dis~~

~~tillation and the residue was fractionally distilled to yield 2.75 g~~

~~(50%) of a 5 *1 mixture (vpc) of 1-n-butylnorcarane (ljj4) and an uniden- 48 tified olefin, bp 108-110° (42 mm) [lit. bp 122.5° (4l mm)]. Separa~~

~~tion of 154 was obtained by preparative vpc on a x 1 0 ’~~

~~1C$ FFAP on 60/80 Chrom W column at 85°. The spectral properties of~~

~~lj?4 were identical to those of a sample obtained from the reaction~~

~~of l-chloro-2-methylcyclohexene (1U5J with n-butyllithium.~~

~~l-n-Butyl-2-methylcyclohexanol (1 5 7). A solution of 10 m l (24 mmol)~~

~~of 2.4 M n-butyllithium in hexane~~

~~was cooled to -78° in a dry ice-~~

~~isopropanol bath. • To this was~~

~~added slowly O.9 8 g (10 mmol) of~~

~~2-methylcyclohexanone (Aldrich~~

Chemical Co.) and the solution was warmed to 25° and stirred for 1 hr. The solution was poured onto ice, the layers were separated, and the aqueous layer was extracted with three 40-ml portions of ether. The combined organic extracts were washed with saturated salt solution and dried over anhydrous magnesium 1 3 1

~~sulfate. The solution was filtered and the solvents were removed on a~~

~~rotary evaporator to yield 1.6 g (100$) of crude 157, contaminated with a small amount of starting ketone.~~

~~(72) A. N. Volkow, A. V. Bogdanova, and G. P. Kugatova-Shemyakina, Zh. Org. Khimii) Vol. 3, No. 2, 316 (1967).~~

l-n-Butyl-2-methylcyclohexene (155)- A mixture of 1.6 g (10 mmol) of crude l-n-butyl-2-methylcyclohexanol (157) and 0.5 g of 85$ phosphoric acid was heated under vacuum to give a mixture of water and olefins which steam distilled from 75-80° (35 mm)* The mixture was diluted with ether, the layers were separated, and the ether layer was washed with saturated salt solution and dried over anhy drous magnesium sulfate. The solution was filtered, the ether was removed by distillation, and the residue was chromatographed on 100 g of Fisher basic alumina to give 0.8^ g (6l$) of 155 contaminated with two other olefins (presumably 2-n-butyl-3-methylcyclohexene and 1- butylidene-2-methylcyclohexene). A pure sample of 155, n^1*8 = 1.4628, was obtained by preparative vpc on a 4 1 x 15' 15$ FFAP on 60/80 chrom

~~P column at 70°. The spectral properties of 155 were identical to those of a sample of 155 obtained from the reaction of l-chloro-2- methylcyclohexene (1^5) with n-butyllithium. 1 3 2~~

~~The Reaction of l-Chloro-2-methylcyclohexene (l4g) with Ehenyllithium.~~

~~The solvents were removed from 55~~

~~ml (76.5 mmol) of 1.4 M phenyl-~~

~~lithium in 70:30 benzene-ether on a a rotary evaporator and were replaced 158 by 3 8 .2 ml of dry tetrahydrofuran. Tie solution was cooled to 0° and~~

4.46 g (38.4 mmol) of N,N,N'^'-tetramethylethylenediamine (TMEDA) followed by 2.0 g (15.3 mmol) of 145 were added. The solution was warmed to reflux and stirred under argon for 5 hr, poured onto ice, and diluted with ether. The layers were separated and the aqueous layer was further extracted with four 75-ml portions of ether. The combined organic extracts were washed with 100 ml each of water and saturated salt solution and dried over anhydrous magnesium sulfate.

The solution was filtered, the solvents were distilled off, and the residue was chromatographed on 200 g of Fisher basic alumina to yield 47a 2.21 g (84$) of 1-phenylnorcarane (158), bp 92-97° (0.65 mm) [lit. bp 104-105° (3.0 ram), ng° « 1.5425].

~~Reaction of l-Chloro-2-methylcyclohexene (l45_) with Methyllithium.~~

The solvent was removed from 19.2 ml (3 8 .5 mmol) of 2.0 M in ether on a rotary evaporator. The solid was cooled to 0° and 17.0 ml of dry tetrahydrofuran, 2.2 g (19-2 mmol) of N,N,N* ,N'-tetramethylethylenediamine and 1.0 g (7*7 mmol) of 145 were sequentially added. The solution was warmed to reflux, stirred under argon for 25 hr, and 133 was poured onto ice. Ether was added, the layers were separated and

~~the aqueous layer was extracted with two 75-ml portions of ether and~~

~~75 ml of 1:1 pentane-ether. The combined organic extracts were washed with saturated salt solution and dried over anhydrous magnesium~~

~~sulfate. The solution was filtered, the solvents were distilled off~~

~~through a glass-helices packed column and the residue was chromato graphed on 150 g of Fisher basic alumina to yield 0.40 g (47$) of~~

~~155), whose properties were identical with those of an authentic~~

~~sample.~~

~~4 1-Methylnorcarane (lJ5g). According to a general literature procedure,~~

21.4 g (80 mmol) of methylene iodide was added slowly to a solution of 5 -0 g (52 mmol) of 1-methylcyclohexene and 5 .2 ml (52 mmol) of diethylzinc (Stauffer) in 25 ml of pentane, under nitrogen. The reaction was exothermic, and occasional cooling was necessary to main tain a gentle reflux. The solution was stirred at 25° for 5 hr, and then poured onto a mixture of ice in dilute hydrochloric acid.

Pentane was added, the layers were separated, and the organic layer was washed with saturated sodium bicarbonate solution, and dried over anhydrous magnesium sulfate. The solution was filtered, the pentane was removed by distillation, and the residue was fractionally dis tilled to yield 2.4 g (42$) of 1§ & bp 120-124° (750 mm), ng3 = 1.4503 47a [lit. bp 124.5° (762 ram), n^° = 1.4480]. The spectral properties of 13 jj> were identical to those of the product derived from the reaction of l-chloro-2-methylcyclohexene (l4jj_) with methyllithium. 1 3 *+ l-Methyl-d3-cyclohexanol (l6l). A solution of 75 ml (0.10 mol) of

~~1.5 M methy1-d3-magne sium iodide~~

~~in ether was prepared by the~~

~~reaction of 15.5 g (0.11 mol) of~~

~~methyl iodide-d3 with 3* 8 g (0.15~~

mol) of magnesium turnings in l6l ether. The solution was cooled in a dry ice-isopropanol "bath and 10.5 g (0 .1 1 mol) of cyclohexanone in 20 ml of ether was slowly added. After warming to 25° and stirring for 1 hr, 20 ml of saturated ammonium chloride solution was added.

The ether solution was decanted and the magnesium salts were washed with additional ether. The combined ethereal extracts were washed with saturated salt solution and dried over anhydrous magnesium sul fate. The solution was filtered and the ether was removed on a rotary evaporator to yield 12.3 g (98$) of l6l, contaminated with a small amount of cyclohexanone. The alcohol was used without further puri fication.

~~T 3 l-Methyl-d3-cyclohexene (162). A mixture of 12.3 g (0.10 mol) of~~

~~l-d3-methyl-cyclohexanol (l6l) and~~

~~2.0 ml of 85% phosphoric acid was~~

~~heated and a mixture of water and~~

~~l-methyl-d3-cyclohexene (162)~~

~~162 distilled from 83 -87°. The layers~~

~~were separated, the organic layer was dried, filtered and distilled to yield 5*50 g (5^3/0 of 16g, bp~~

~~105-110° (750 mm), n^ 1* 8 = 1.4577* Mass spectral analysis indicated~~

~~162 to be 70$ d3, 25$ d2, and 5$ d1.~~

~~(73) T- G. Selin and R. West, J. Amer. Chem. Soc. , 84, 1863 (1962).~~

~~trans-l,2-Dichloro-l-methyl-d3-cyclohexane (216,). This reaction was~~

~~carried out by the same procedure~~

~~used to prepare trans-1 ,2-dichloro-~~

~~1-methylcyclohexane (152). Thus,~~

~~5*5 g (55*6 mmol) of l-d3 -methyl-~~

cyclohexene (162) was reacted with 216 15.3 g (55*6 mmol) of iodobenzene dichloride in 100 ml of carbon tetrachloride under nitrogen. Regenera tion of iodobenzene dichloride with chlorine gas, filtration, work-up, and distillation gave 6 .5 g (67^) 218, bp 100-110° (25 mm), n^2*5 =

~~1.4887. l-Chloro-2-methyl-d3-cyclohexene (l60). This compound was prepared by~~

~~the same method used to prepare~~

~~undeuterated l-chloro-2-methyl- ,cd3 11 cyclohexene (145). Thus, 6 .5 g of Cl a' trans-1 ,2-dichloro-l-methyl-d3- cyclohexane (218) was added to a 1 3 6~~

~~sodium amide solution prepared by the addition of 2.1 g (93 mmol) of~~

~~sodium to 65 ml of liquid ammonia containing 0.15 g of ferric nitrate,~~

and the suspension was stirred at reflux for 8 hr. Neutralization with ammonium chloride, work-up as described above and distillation gave 2.4 g (4$$) of l60, bp 75-80°, n^°*a = 1.4809. Mass spectral

~~analysis indicated that 160 was 8l$> d3 , 15% d2, and 4$ d]_. The ir~~

~~spectra (neat) showed absorptions at 3 *^-0 , 4.72, 6.00, 6.9 8?~~

~~7.52, 7.98, 9.81, and 10.10 \i.~~

~~The Reaction of l-Chloro-2-methyl-d3-cyclohexene (l6o) with n-Butyl- lithium. A solution of 3-7 ml (9-0 mmol) of 2.4 M n-butyllithium in~~

~~hexane was cooled to 0° and 0 .5 2 g~~

~~D (4.5 mmol) of N,N,N',N'-tetra-~~

~~methylethylenediamine (TMEDA)~~

~~followed by 0.24 g (l. 8 mmol) of~~

~~160, were added. The solution~~

~~was warmed to reflux and stirred~~

~~under argon for 1.5 hr. The solu-~~

~~tion was then poured onto ice,~~

~~diluted with ether, and the layers n-Bu were separated. The aqueous layer~~

~~166 was extracted with three 40-ml~~

~~portions of 1 :1 pentane-ether.~~

~~The combined organic extracts were~~

~~washed with two 50-ml portions of~~

~~1 6 7 water and 50 ml of saturated salt solution, and were dried over anhy~~

~~drous magnesium sulfate. The solution was filtered, the solvents were~~

~~removed hy distillation and the residue was molecularly distilled to~~

~~yield 0 .20 g (72$) of a 5:1:! mixture of l-n-butylnorcarane-7,7-d2~~

~~(165), l-n-butyl-2-methyl-d3-cyclohexene (3.66), and 2-n-butyl-3-~~

~~methyl-d3-cyclohexene (167). Compound l6j)_, which was 14$ d3 , 62$ d2,~~

~~14$ dx, and 10$ do by mass spectral analysis, was separated from the~~

~~mixture of cyclohexenes by preparative vpc on a x 15' 15$ FFAP~~

~~on 60/80 Chrom P column at 75 °* The mixture of 166 and 167 was 4l$~~

~~d3, 38$ d2, 11$ dj., and 9$ d0.~~

~~The nmr spectrum of 165 was similar to that of 1-n-butylnorcarane~~

~~(154), except for the decrease in intensity of the cyclopropyl absorp~~

~~tions in the t 9 -1 0 region which showed the 7-position to be 85$~~

~~deuterated. The spectral properties of 165 were: nmr (CCI4/TMS) T~~

~~8.37 (4h, broad m), 8.74 (1IH, broad m), and 9.11 (3H, broad m)j~~

~~n22 = 1.4560. The mixture of cyclohexenes 166 and 167 was identified~~

~~by comparison with the nmr spectra of a mixture of l-n-butyl-2-methyl-~~

~~cyclohexene (15_5_) and 2-n-butyl-3-methylcyclohexene (217). The~~

~~spectra were similar except for the disappearance of the absorption~~

~~of the vinyl group of 15J5 at t 8.38 .~~

~~Reaction of l-Chloro-2-methyl-d3-cyclohexene (l6o) with Methyllithium.~~

~~This reaction was carried out as described for the reaction of methyllithium with l-chloro-2-methylcyclohexene (l4j?_). A solution of~~

~~3.7 ml (7*5 mmol) of 2.0 M methyllithium in tetrahydrofuran containing 1 3 8~~

~~0.87 g (7.5 mmol) of N,N,N,,]!r-~~

~~tetramethylethylenediamine and~~

~~0.20 g (1.5 mmol) of 3.60 was~~

~~refluxed under argon for 22 hr.~~

~~163 Work-up as described and mole cular distillation gave 50 mg (30 %)~~

of l-methylnorcarane-7, 7-d2 (163 ) which was 10% d3, 70% d2, 13% d l5 and 7% by mass spectral analysis. The nmr of 16b was similar to that of l-methylnorcarane (155O , except that very little cyclopropyl proton absorption was seen in the nmr. Integration of the nmr spectrum indicated that the 7-position was at least 7^% deuterated. The ir showed absorptions at 3 *50, b.56, ^.8 2, 7*02, 8.13 , and 9*77 M-.

~~The Reaction of l-Chloro-2-methyl-d3-cyclohexene (l6o) with Phenyl- lithium. The solvent was removed from 2.5 ml (5-5 mmol) of 2.2 M~~

~~phenyllithium in 70:30 benzene-~~

~~T> D ether on a rotary evaporator. The~~

~~residue was cooled and 2 .5 ml of~~

~~^ dry tetrahydrofuran, 0.6b g (5-5~~

~~164 mmol) of N,N,N' ,N'-tetramethyl-~~

ethylenediamine, and 0.15 g (1 .1 mmol) of 160 were added sequentially. The mixture was warmed to reflux and was stirred under argon for 6 hr. The solution was poured onto ice, ether was added, the layers were separated, and the aqueous layer was extracted with two 30 -ml portions each of ether and 1 :1 ether-pentane. The combined organic extracts were washed with two

~~50-ml portions of water and 50 ml of saturated salt solution, and were~~

~~dried over anhydrous sodium sulfate. The solution was filtered, the~~

solvents were removed on a rotary evaporator, and the residue was molecularly distilled to yield 0.13 g (68%) of l-phenylnorcarane-T? 7- d2 (l6b), which was 9.8% d3, 6j.b% d2 , 17*5$ d1? and 5-3 $ do by mass

~~spectral analysis. Analysis of the 7-position by nmr indicated this position to be 79$ deuterated.~~

~~Preparation of trans-l,2-Dichloro-l-ethylcyclohexane (217). Nitrogen~~

~~was bubbled through a suspension~~

of 2lb.3 g (0.78 mol) of iodo- Cl benzene dichloride in 1 .6 £ of Cl os carbon tetrachloride for 20 min. H To the suspension was then added 218 8 6 .0 g (0 .7 8 mol) of 1-ethylcyclohexene and the solution was warmed while being irradiated (through the ryrex flask) by a Hanovia 30620 quartz ultraviolet lamp. The solution cleared at 60-70° and was heated at reflux for 0.5 hr (no further irradiation). The flask was then cooled in an ice-salt bath and protected by a dry ice-isopropanol condensor. Chlorine was passed through a sulfuric acid scrubber through a fritted gas inlet and then into the flask over a 3 hr period. Most of the excess chlorine was then pulled off through water aspiration and the regenerated iodobenzene dichloride was filtered off. The filtrate was washed with saturated solutions of sodium carbonate, sodium bicarbonate, sodium

~~thiosulfate, and sodium chloride, nd was dried over anhydrous magne~~

~~sium sulfate. The solution was filtered, the carbon tetrachloride was distilled off and the residue was fractionally distilled to yield~~

86.0 g (6l$) of 2l8, bp 115-120° (37 mm). The spectral properties 74 of 217 were: nmr (CCI4/TMS) T 5*74 (1H, broad s), 7*23-8.71 (10H, broad m), 8 .9 6 (3H, t, J = 7.2 Hz); ir (neat) 3 .3 6 , 6.94, 8.65,

~~10.05, 10.76, 11.81, 11.9 2, 12.62, 13 .68, and 14.40 m n34* 3 = 1.4892.~~

~~(74) For an ir of 218, see ref. 70.~~

~~l-Chloro-2-ethylcyclohexene (178). A sodium amide solution was pre~~

~~pared by the addition of 32.4 g~~

~~(l. 4l mol) of sodium in small~~

~~chunks to 1-X of liquid ammonia~~

~~containing 0.4 g of ferric~~

~~nitrate hydrate and stirring for~~

0.5 hr after addition. To this solution was added 8 5 .0 g (0.47 mol) of trans-1 ,2-dichloroethylcyclo- hexane (23-8) over a 20 min period and the solution was stirred at reflux for 8 hr. At this point, 100 g (1 .9 mol) of solid ammonium chloride was carefully added in small portions through a piece of Gooch tubing. Ether (300 ml) was added, the dry ice-isopropanol condensors were removed and the ammonia was allowed to boil off overnight. Water 141

~~(300 ml) was then added to the ethereal mixture and the layers were~~

separated. The aqueous layer was extracted with two 200-ml portions of ether and 200 ml of pentane and the combined organic extracts were dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were distilled off, and the residue was fractionally distilled to yield 27.4 g (40.236) of 178, bp 90-92° (38 mm), n^5' 4 =

1.4830. An analytical sample was prepared by preparative vpc on a x 1 0 1 10$ SE-30 on 60/80 Chrom W column at 100°. Lower boiling material collected in a dry ice-isopropanol cooled trap was re distilled at atmospheric pressure to yield 2 .0 g (4.0$>) of vinylidene- cyclohexane, bp 120-125°, n^5 , 4 = 1.4830.

~~The spectral properties of 178 were: nmr (CCI4/TMS) t 7-45-8.14~~

~~(6h, m, sharp peaks at 7- 76 and 7.8 9), 8.14-8.73 (4h, m, sharp peak at 8.3 5 ), 9-03 (3H, t, J = 7-1 Hz); ir (neat) 3-38, 5-98, 6.84, 7-46,~~

~~10.05, and 12.19 M>> n^5 ' 4 = 1.4830.~~

~~Anal. Calcd for CaH13 Cl: C, 66.43; H, 9-06; Cl, 24.51.~~

~~Found: C, 66.35; H, 9-37; Cl, 24.63 .~~

~~Reaction of l-Chloro-2-ethylcyclohexene (178) with n-Butyllithium.~~

~~A. solution of 28.2 ml (69 mmol) of~~

~~CH3 2.4 M n-butyllithium in hexane was~~

~~cooled to 0° and 4.0 g (34.5 mmol)~~

~~of N,N,IT,N' -tetramethylethylene-~~

~~diamine followed by 2 .0 g (13-8 m mmol) of 178 were added. The solution was stirred at 25° for 36 hr~~

~~under argon. After pouring onto~~

~~ice, the layers were separated and OC-» the aqueous layer was extracted~~

~~180 with two 50-ml portions each of ether and pentane. The combined~~

~~organic extracts were washed with~~

~~n-Bu saturated salt solution and dried over anhydrous magnesium sulfate.~~

~~The solution was filtered, the~~

~~solvents were distilled off, and 181 the residue was chromatographed on~~

~~250 g of Fisher basic alumina to yield 1 .3 g (57%) of a 3:1:1 mixture~~

~~(vpc) of l-n-butyl-syn-7-methylnorcarane (ljg), l-n-butyl-2-ethylcyclohexene (180), and (possibly) 1-n-butyl-3 -ethylcyclohexene (l8l).~~

~~The structures of 179 and l8j were deduced from spectral properties, while 180 was identified by spectral comparison with an authentic sample. These products were separated by preparative vpc on a x~~

~~10' 10% FFAP on 6 0/80 Chrom W column at 60°.~~

~~The spectral properties of 179 were: nmr (CCI4/TMS) t 7-85-9-36~~

~~(2HH, broad m, sharp peaks at T 8.78, 9.03, and 9-H), ir (CC14 soln)~~

~~3 .3 7 , 6.84, 7.28 , 8.03 , and 11.58 \i,~~

~~Anal. Calcd for Ci2H22: C, 86.66; H, 13-34.~~

~~Found: C, 86.42; H, 13.43. 143~~

~~The spectral properties of l80 -were: nmr (CC14/TMS) t 7-77-8.24~~

~~(8h, broad m), 8.24-8.88 (8h, broad m), 8.88-9-37 (6h, broad m, sharp~~

peaks at 9*08 and 9-18); (CC14 soln) 3-40, 6.01, 6.85, 7*28, 8.03*

~~and 11-59 M-* Calcd m/e: 166.1721. Found: 166.1724.~~

~~The spectral properties of l8l were: nmr (CC14/TMS) t 5*78 (1H,~~

~~broad s), 7*72-9.40 (21H, broad m, sharp peaks at 8.72 and 9.03); ir~~

~~(CC14 soln) 3-47, 6.02, 6.83 , 7.28, and 8 .8 6 p,; Calcd m/e: 166.1721.~~

~~Found: 166.1724.~~

~~Preparation of 2-Ethylcyclohexanone (219). To a solution of 10.1 g~~

~~(0 .1 mol) of diisopropylamine in 25 ml of tetrahydrofuran cooled to~~

~~0° was added dropwise 4l. 7 ml (0.1 mol) of 2.4 M n-butyllithium in~~

~~hexane. The resulting solution of lithium diisopropylamide -was~~

~~cooled to -78° (now a suspension) and 9*8 g (0 .1 mol) of cyclohexanone~~

~~was added slowly. The solution was warmed to 0° and 1 5 .6 g (0.1 mol)~~

~~of ethyliodide was added dropwise. The solution was allowed to warm~~

~~to 25° and was stirred for 4 days under nitrogen. The solution was~~

~~diluted with ether and washed with three 100-ml portions of 1 .0 N~~

~~aqueous citric acid. The aqueous washings were extracted with three~~

~~100-ml portions of ether. The combined organic extracts were then washed with saturated salt solution and dried over anhydrous magnesium~~

~~sulfate. The solvent was distilled off and the residue was fractionally 75 distilled to yield 2 .6 g (21$) of 219, "bp 70-71° (12 mm) [lit. bp~~

~~67-68° (12 mm)]. The infrared spectrum was identical with that pre- 76 viously published. 144~~

~~(75) H. Suhr, et. al., Justus Liebigs Ann. Chem., 649, 53 (1961).~~

~~(76) Satler IR No. 24291.~~

~~Preparation of the Epimeric 1-n-Butyl-2-e thylcyclohexanols (220). A~~

~~solution of 6 .7 ml (l6 mmol) of~~

~~2.4 M n-butyllithium in hexane was~~

~~cooled to -78° in a dry ice-~~

~~isopropanol bath and 1 .0 g (8 .0~~

~~220 mmol) of 2-ethylcyclohexanone~~

(219) in 5 ml of ether was added slowly over 10 min. The solution was filtered, the solvent was' removed on a rotary evaporator, and the residue (1.4 g, 10C$>) of epimeric l-n-butyl-2-ethylcyclohexanols (220) (contaminated with ca.

~~15$ of 219) was used in the following reaction without further puri fication.~~

~~The spectral properties of the epimeric mixture were: nmr (CC14/~~

~~TMS) t 7.50-8.95 (17H, broad m), 9.08 (6h, broad s); ir (neat) 2.86,~~

~~20 O 3.40, 6.83 , 7.26, and 10.22 n; n^ * = 1.4525. Calcd m/e for C 12H240:~~

184.1827. Found: 184.1829. l-n-Butyl-2-ethylcyclohexene (l80). A mixture of 1.4 g (8.0 mmol) of crude l-n-butyl-2-ethylcyclohexanol (220) and 0.5 ml of 85% phosphoric acid was heated while under 35 mm pressure. A mixture of water and 180 containing two other olefins, distilled from 70-80°. The distillate was diluted with pentane, and the pentane solution was washed with saturated salt solution, and dried over anhydrous magnesium sulfate.

~~Hie solution was filtered, the pentane was distilled off, and the residue was chromatographed on.100 g of Fisher basic alumina to yield~~

0.94 g (71%) of 180 contaminated with two other olefins. A pure sample of 180 was obtained by preparative vpc on a x 1 0 ' 4 :1 glycerol-silver nitrate on 60/80 Firebrick at 55°» The spectral properties of l8o were identical to those described of a sample ob tained from the n-butyllithium reaction of 178. Calcd m/e: 166.1721.

~~Found: 166.1724.~~

~~2-n-Butyl-2-chlorocyclohexanone (221). This compound was prepared by~~

~~the chlorination of 2-n-butyl-~~

~~cyclohexanone according to the n-Bu 7 8 method of Johnson. The 2-n-~~

~~butylcyclohexanone was itself pre~~

~~221 pared by the method of Stork and 77 Dowd. Chloride 221 had spectral properties identical to those reported by Taylor, from a sample pre- 7 9 pared in a slightly different fashion.~~

~~(77) G. Stork and S. R. Dowd, J. Amer. Chem. Soc., 85, 2178 (1963).~~

~~(78) E. Warnoff, D. G. Martin, and W. S. Johnson, Org. Syntheses, Coll. Vol. 4, 162 (1963). 146~~

~~(79) K. G. Taylor, W. E. Hobbs, M. S. Clark, and J. Chaney, J. Org. Chem., 37, 2436 (1972).~~

~~80 2-n-Butylcyclohexenone (183 ). The method of Corey was adopted for~~

~~the dehydrochlorination of 2-n-~~

~~butyl-2-chlorocyclohexanone (221). n-Bu A solution of 17.4 g (0 .2 0 mol) of~~

~~lithium bromide in 225 ml of dry~~

~~N,N-dimethylformamide containing~~

2 2 .1 g (0 .3 0 mol) of lithium car bonate was warmed to 110° in an oil bath, and 25.3 g (0*13 mol) of 222 was added. Die bath was warmed quickly to I3 O0 and this temperature was maintained for 1 hr. The solution was cooled and poured into a solution of 30 ml of glacial acetic acid in 200 ml of water, and this solution was extracted with four 200-ml portions of methylene chloride.

~~The combined methylene chloride extracts were then washed with five~~

100-ml portions of water, 200-ral each of saturated solutions of sodium bicarbonate and salt, and dried over anhydrous magnesium sulfate. The solution was filtered, the methylene chloride was distilled off, and the residue was fractionally distilled to yield 1 5 .1 g (74$) of a 5 :1 mixture (nmr) of 183 and 2-butylidenecyclohexanone (222), bp 92-95° 7 9 (2.5 mm) [lit. bp 8l.5-92 (1.6 mm)]. This method of dehydrochlorina- 73 tion of 220 is an improvement of the method previously described. (80) E. J. Corey and J. G. Welch, J. Amer. Chem. Soc., 88, 5736 (1965).

~~Diethyl(3-ethyl-2-n-butylcyclohexene)phosphate (185). Following the 53 general procedure of Ireland, 0 II a solution of lithium diethyl- 0-P(0Et)2 cuprate was prepared by the addi~~

~~i-Bu tion of 58.O ml (52.4 mmol) of~~

~~0.9 M ethylllthium in ether to a 185 suspension of 5 .0 g (2 6 .2 mmol) of~~

~~cuprous iodide in 50 ml of ether at -78° under argon, and the mixture~~

~~■was stirred at -50° for 0.5 hr. The solution was again cooled to~~

~~-78° and 2.0 g (13 .I mmol) of 2-n-butylcyclohexenone (185) in 5 “1 of~~

~~ether was slowly added. Ihe solution was allowed to warm to 0° over~~

~~15 min and was stirred at 0° for an additional 15 min. The enolate~~

~~ion formed was reacted with 60.3 g (6 0 .0 mmol) of diethylphosphoro-~~

~~chloridate at -20°, and the solution was allowed to warm to 25° and~~

~~stirred for 30 min. After pouring onto ice the layers were separated~~

~~and the aqueous layer was extracted with four 60-ml portions of ether.~~

~~The combined organic extracts were then washed with saturated salt~~

~~solution and dried over anhydrous magnesium sulfate. The solution~~

~~was filtered, the ether was removed on a rotary evaporator to yield~~

~~6.8 g of crude phosphate, which was used in the following reaction without further purification. Chromatography on 250 g of silica gel (ether-pentane) of crude~~

~~phosphate prepared in a separate reaction (same amounts) gave 0 .9 0 g~~

~~(22#) of l85_ along with 0.8 g (4C$>) of recovered 185. The spectral properties of 185 were: nmr (CC14/TMS) t 5 .9 8 (4h, J = 5-5 Hz), 7.16-~~

~~9.57 (2TH, broad m, containing a 6h, t, J = 7*2 Hz, centered at T~~

~~8.67); ir (neat) 3 -3 8 , 5-82, 5-91, 6.94, 7.30 , 7.83 , 8.82, 9.62,~~

~~IO.36 , 12.20, 12.51, and 13.32 jji. Calcd m/e for CxeHaxO^P: 318 .1960.~~

~~Found: 318 .1966.~~

~~Preparation of 2-n-Butyl-3-ethyIcyclohexene (l8l). To a solution of~~

~~0 .9 1 g (0.13 mol) of lithium in 100 ml of ethylamine at 0° was added a solution of 5*2 g (13*1 mmol, theoretical) of crude 185 in 3-9 g~~

(39*1 mmol) of t-butyl alcohol, over a 10 min period. The solution was stirred for 25 min at 0° and poured onto ice. Ether was added, the layers were separated and the aqueous layer was extracted with two

75-ml portions each of ether and pentane. The organic extracts were then washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solution was filtered, the solvents were dis tilled off, and the residue was chromatographed on 200 g of Fisher basic alumina to yield 0 .2 6 g (loverall for two steps) of l8l.

~~Reaction of l-Chloro-2-ethyIcyclohexene (178) with Hienyllithium. The~~

The solvent was removed from U9.5 ml (69 mmol) of 1.4 M phenyllithium in 70:30 benzene-ether on a rotary evaporator. The flask was cooled to 0° and 35 ml of dry tetrahydrofuran followed by 8.0 g (69 mmol) of 149

~~N, N, N *, N 1 -tetramethylethylene-~~

~~diamine and 2 .0 g (1 3.8 mmol) of~~

~~178 were added sequentially. The~~

~~solution was warmed to reflux and~~

~~187 was stirred under argon for 12~~

~~hr. The solution was then poured~~

~~onto ice, ether was added, the layers were separated,aand the aqueous~~

~~layer was extracted with two 75-ml portions each of ether and 1 :1~~

~~ether-pentane. The combined organic extracts were washed with 100 ml~~

~~of water and 100 ml of saturated salt solution, and were dried over~~

~~anhydrous magnesium sulfate. The solution was filtered, the solvents were removed on a rotary evaporator, and the residue was chromatographed~~

~~on 225 g of Fisher basic alumina to give 0.J6 g (30$) of l-ethyl-2-~~

~~phenyIcyclohexene (187). An analytical sample was obtained by pre~~

~~parative vpc on a 4" x 101 10$ SE-30 on 60/80 Chrom W column at l40°.~~

~~Compound 187 was identified by the similarity of the aliphatic region~~

~~of its nmr spectrum to that of 178. The methyl triplet at T 9 « H is particularly characteristic.~~

~~The spectral properties of l 8 j were: nmr (CCI4/TMS) t 2.88 (5H, m), 7.58-8.83 (10H, broad m), 9.11 (3H, t, J * 7.2 Hz); ir (neat)~~

~~3.40, 5.14, 5.33, 5.56, 6.25, 6.84, 7-3 0 , 8.80, 9.3 8 , 9.73, 13 -21, and 14.33 M>, = 1.5243-~~

~~Anal. Calcd for C^His: C, 90.26; H, 9*74.~~

~~Found: C, 89.99*, H, 10.16. 1 5 0~~

~~Reaction of l-Chloro-2-ethy Icyclohexene (178) with Me thy Hi thrum.~~

~~The solvent was removed from Tk.J>~~

~~ml (0.14 mol) of 1.9 M methyl-~~

~~lithium in ether on a rotary eva oc porator. The flask was cooled to 0 ° under argon and 50 ml of dry 188 tetrahydrofuran, 6 .0 g (52 mmol)~~

~~of E,N,N',N 1 -tetramethylethylene-~~

~~diamine, and 5 .0 g (21 mmol) of~~

~~178 were added sequentially. The~~

~~solution was warmed to reflux and~~

189 stirred for 92 hr under argon, and then poured onto ice. Ether was added, the layers were separated, and the aqueous layer was extracted with two 75-ral portions each of ether and 1:1 pentane-ether. The combined organic extracts were washed with five 50-ml portions of water, and 75 ml of saturated salt solution, and were dried over anhy drous magnesium sulfate. The solution was filtered, the solvents were distilled off, and the residue was distilled to yield 0.5^ g (2*$) of a 4:1 mixture of 1-ethyl-2-methyIcyclohexene (188) and a second olefin tentatively identified as 3 -ethyl-2-methyIcyclohexene (189), 81 bp 135 -137° (7^5 mm) [lit. bp 78° (56 mm)]. The nmr of the mixture was very similar to a sample of 188 obtained from the dehydration of

~~1-ethyl-2-methylcyclohexanol (225). In this dehydration a minor inseparable olefin (20fi) having an olefinic proton is seen in the nmr,~~

~~and is presumably 2-ethyl-3-methylcyclohexene. The chemical shift of~~

~~the proton from the later compound is at slightly higher field than~~

~~that of 189.~~

~~The spectral properties of the mixture were: nmr (CC14/TMS) t~~

~~4 .65 (0.2H, m), 7.67-8 .6 8 (13H, broad m), 9.O6 (3H, broadened t, J =~~

~~7.2 Hz); ir(CC1 4 soln) 3-38, 6.80, 7.88, 8.78, and 9 .6 8 \i. An analytical sample of 188 was obtained by preparative vpc on a ^ " x~~

~~15' 15$ FFAP on 60/80 Chrom P column at 65°.~~

~~Anal. Calcd for C9H X6: C, 87.02; H, 12.98.~~

Found: C, 87.07; H, 12.99. l-Ethyl-2-methylcyclohexene (188). This compound was prepared by a ax literature procedure except that dehydration of l-ethyl-2-methylcyclohexanol (223 ) was effected by steam distillation from 85% phos phoric acid. A small olefinic absorption could be seen in the nmr of

~~187? presumably due to the presence of 2-ethyl-3-methylcyclohexene.~~

~~(8l) V. T. Aleksanyan, et. al., Izvest. Akad. Nauk S.S.S.R., Otdel. ’ Khim. Nauk., 84 (i960). This reference contains a discussion of the dehydration of 1,2-dialkylcyclohexanols.~~

~~2-Chlorocyclohexenecarboxaldehyde (193). This compound was prepared~~

~~from cyclohexanone according to 82 the procedure of Paquette. 152~~

~~(82) L. A. Paquette, B. A. Johnson, and F. M. Hinga, Org. Syntheses, Coll. Vol. 5, 215 (1972).~~

~~l-Chloro-2-vinyIcyclohexene (lgg). To a mechanically stirred suspen~~

~~sion of 100 g (0.28 mol) of~~

~~methyltriphenylphosphonium bromide~~

~~(Aldrich Chemical Co. ) in 400 ml~~

~~of dry ether was added slowly 133 33S. ml (O.28 mol) of 2.1 M n-butyllithium in hexane and the solution~~

~~was stirred at 25° for 3 hr. A solution of 37*6 g (0.26 mol) of 2-~~

~~chlorocyclohexenecarboxaldehyde (193 ) in 50 nil of ether was slowly~~

~~added over 1 hr, and the mixture was refluxed for 18 hr. The suspen~~

~~sion was then filtered and the solid residue was thoroughly washed~~

~~with ether. The filtrate was washed with saturated salt solution and~~

~~dried over anhydrous magnesium sulfate. The solution was filtered,~~

~~the solvents were distilled off, and the residue was fractionally~~

~~distilled through a glass helices packed column to yield 17.2 g (kyjo)~~

of pure 192, bp 87-89° (20- mm), nj3 = 1.5255*

~~The spectral properties of 192 were: nmr (CCI4/IMS) T 3*00 (1H,~~

~~q, J = 7*0 Hz), 4.82 (2H, t, J = 10.5 Hz), 7*50-8.00 (4h, broad m),~~

~~8.OO-8 .5 6 (4h, broad m); ir (neat) 3*37, 6.12, 6.90, 6.97, 7*07, 7*44,~~

~~8.12, 9.1k, 9.72, 10.11 (d), 11.03 , and 12.24 it. 153~~

~~Anal. Calcd for C8HXiCl: C, 67-37; H, 7*77; Cl, 24.86.~~

~~Found: C, 67.28; H, 7.90; Cl, 24.14.~~

~~Reaction of 2-Chloro-l-vinylcyclohexene (192) with n-Butyllithium. To~~

~~a solution of 17*5 ml (35 mmol)~~

~~of 2.0 M n-butyllithium in hexane~~

~~at 0°, was added 1 ,0 g (7 .0 mmol)~~

~~of 192. The solution was warmed~~

~~to reflux, stirred for 25 hr,~~

and then carefully poured onto ice. The layers were separated and the aqueous layer was extracted with two 50-ml portions each of ether and 1:1 ether-pentane. The combined organic extracts were washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solution was fil tered, the solvents were removed by distillation and 'the residue was chromatographed on 150 g of Fisher basic alumina to yield 0.64 g (5^&) of 3-hexylidenecyclohexene (194). The spectral properties of 194 were: nmr (CCI4/TMS) t 3.86-4.58 (2H, m), 4.58-5.02 (1H, broad t, J = 7.0 cps), 7.5-9*32 (15H, m, sharp absorbances at T 8 .6 7 and 9.1°); ir

~~(CC14 soln) 3-35, 6.09, 6.83 , 6.95, 7.27, 7.49, 8.00, 9.48, IO.63 , and 11.50 11; n j 5 = 1.4933.~~

~~Anal. Calcd for C X2H20: C, 87.73; H, 12.27.~~

~~Found: C, 87.86; H, 12.33* /~~

154 3-Hexylidenecyclohexene (194). To a suspension of 95*0 g (0.22 mol') of n-hexyltriphenylphosphonium bromide in 250 ml of dry ether was added 110 ml (0 .2 2 mol) of 2 .0 M n-butyllithium in hexane, via a syringe. The solution was stirred at 25° for 4 hr, and 20.6 g (0.21 mol) of freshly distilled cyclohexenone was slowly added. The mix ture was refluxed for 24 hr, allowed to cool, and then filtered. The filtrate was washed with saturated salt solution and dried over anhy drous magnesium sulfate. The solution was filtered, the ether was distilled off, and the residue was fractionally distilled to yield

~~2 .8 g (8^) of the epimeric hexylidenes 19 4; bp 56-58° (0.45 ““ )•~~

~~The spectral properties of 194 were identical to those of a sample of 194 obtained from the reaction of 192 with n-butyllithium.~~

~~Chloromethylenenorbornane_ _ __ (199)«_ In a modification of a procedure of Seyferth, 53 ml (0.10 mol) of 1 .9 M n-butyllithium in hexane~~

~~was added over a 1 hr period at~~

~~-35 ° to a solution of 30 g (0 .1 1 CHC1 mol) of triphenylphosphine and 11 g~~

~~(0.13 mol) of methylene chloride~~

~~in 200 ml of dry tetrahydrofuran.~~

At this point 11 g (0.10 mol) of norcamphor in 50 ml of tetrahydrofuran was added and the solution was heated at reflux for 8 hr. The solution was then cooled, trans ferred to a separatory funnel, and shaken with 100 ml portions each of ether and water. The layers were separated and the aqueous phase was extracted with three 150-ml portions of pentane. The combined

~~organic extracts were washed with saturated salt solution and dried~~

~~over anhydrous magnesium sulfate. Ihe solution was filtered, the~~

~~solvents were removed by distillation, and the residue was fractionally~~

~~distilled through a glass helices packed column to yield 2 .0 g (l4$)~~

~~of 199, hp 65-67° (55 mm). An analytically pure sample was obtained~~

~~by preparative vpc on a x 10’ 1C$ SE-30 on 60/80 Chrom W column~~

~~at 90°. The spectral properties of 199 were; nmr (CCI4/TMS) t 4.23~~

~~(0.4h, pseudo triplet), 4.48 (0.6H, broad s), 6.8l (0.6h, broad s),~~

~~7.23 (0.4H, broad s), 7.61 (1H, broad s), 7.94 (2H, m), 8.2-9.2 (6h, m); ir (neat) 3.33s 6.03 , 6.9 1, 7.00, 7.59s 7.68, 7*92, 10.6l, 11.34,~~

~~11.88, and 12.67 n; n^3 * 2 = 1.5647.~~

~~Anal. Calcd for csH XiCl: C, 67.37; H, 7*77; Cl, 24.86.~~

~~Found: C, 67.06; H, 7.98; Cl, 24.70.~~

~~Reaction of 2-Chloromethylenenorbornane (199) with n-Butyllithium. The~~

~~solvent was removed from 7.4 ml~~

~~(l4. 0 mmol) of 1.9 M n-butyl~~

~~lithium in hexane on a rotary~~

~~evaporator. The residue was cooled~~

~~200 4o 0° and 6 ml of dry tetrahydro~~

~~furan was added followed by 0 .2 2 g~~

(1.54 mmol) of 199. The solutionwas allowed to warm to 25° and stirred for 0.5 hr. It was then poured onto ice, diluted with ether, the layers were separated, and the aqueous layer was extracted with three 3O-ml portions of ether and two 30-®l portions of pentane. The

~~combined organic extracts were washed with saturated salt solution~~

~~and dried over anhydrous magnesium sulfate. The solution was fil~~

~~tered, the solvents were distilled off through a glass helices packed~~

~~column, and the residue was chromatographed on 60 g of Fisher basic~~

~~alumina (pentane) to yield 0.22 g (87$) of a mixture of epimeric~~

~~pentylidenenorbomanes (200) whose spectral properties were identical to those of a sample prepared by the Wittig reaction of norcamphor with n-pentylidenetriphenylphosphorane.~~

2-Fentylidenenorbornane (200). To a mixture of 63.9 g (0*155 mol) of n-pentyltriphenylphosphonium bromide in 300 ml of dry ether was slowly added 90 ml (0.17 mol) of 1.9 M n-butyllithium in hexane and the solution stirred at 25° for 4 hours. The solution was cooled to 0°, a solution of 1J.6 g (0 .1 6 mol) of norcamphor in 50 ml ether was added slowly and the solution was refluxed for 20 hours. Excess ylid and n-butyllithium were destroyed by the addition of a saturated aqueous ammonium chloride solution. The solution was decanted and the layers were separated. The solid residue was washed with ether • and the combined organic fractions were washed with saturated salt solution and dried over anhydrous magnesium sulfate. The solution was filtered and the residue was fractionally distilled through a glass helices packed column to give 9*55 g (37*5$) of 200? bp 106-107°

~~(23-24 mm). The spectral properties of 200 were: nmr (CCI4/TMS) t~~

~~4.62-5.20 (1H, m), 7.10 (broad singlet), 7.38-9*28 (l8H, m)-, ir (neat) 157~~

~~5-37, 5-93 (weak), 6.9 0, 7.28, 7.71, 10.70, and 11.89 p,; ng4 = 1.4743.~~

~~Anal. Calcd for C12H2o: c> 87. 73» H, 12.27.~~

~~Found: C, 88.02; H, 12.42.~~

~~Reaction of 2-Chloromethylenenorbomane (199) with Fhenyllithium.~~

~~A solution of 0.20 g (1.4 imnol)~~

~~of 199 in 6 .1 ml (14.0 mmol) of~~

~~2 .3 M phenyllithium in 70:30~~

~~benzene-ether was heated at reflux~~

~~201 for 24 hr. The solution was~~

~~poured onto ice and diluted with 25~~

~~ml of ether . The layers were~~

~~separated and the aqueous phase~~

~~H was extracted with two 25-ml por~~

~~tions each of ether and pentane.~~

~~202 The combined organic extracts were~~

then washed with saturated salt solution and were dried over anhydrous magnesium sulfate. The drying agent was removed byfiltration and the solvents were removed on a rotary evaporator and the residuewas chromatographed on 60 g of

~~Fisher basic alumina (hexane) to yield 0.21 g (84$) of a 52:47 mixture of the epimeric E- and Z-2-benzilidenenorbomanes (201 and 202, respectively). These isomers were cleanly separated on a x 12'~~

~~10$ FFAP on 45/60 Chrom W column at 150° to give pure samples of each epimer. 158~~

~~Hie spectral properties of 201 were: nmr (CC14/hyE) T 2 .89 (5H, s), 3*98 (1H, broad s), 6.77 (lH, m), 7«33-8.00 (3H, broad m); ir~~

~~(CC14 soln) 3.36, 5.14, 5.30, 5-56, 6.01, 6.2k, 6.J1, 6.91, 7.27,~~

~~8.71, 9.29, 9.72, 10.60, 10.71, 11.00, and 11.35 nj4 = 1.5037.~~

~~Exact m/e Calcd for Cx4Hi6: 184.1252. Found: 184.1255.~~

Hie spectral properties of 202 were: nmr (CC14/TMS) t 2.82 (5H, s), 3 .8 1 (1H, broad s), 7.10-7 .8 2 (4h, broad m), 7.82-9.40 (6h, broad m); ir (CC14 soln) 3 .34 , 6.03 , 6.26, 6.91, 7-28, 7.71, 8.04,

~~8.97, and 11.02 \l -, ng4 = 1.5045. Calcd m/e for C14H16: 184.1252.~~

Found: 184.1255 *

E- and Z-2-Benzylidenenorbornanes (201 and 202). In a modification of 83 a procedure described by Fieser, a mixture of 5*5 g (0.043 mol) of benzyl chloride and 7 .7 ml (0.044 mol) of triethyl phosphite was heated at reflux for 1 hr and then cooled. Hie phosphonate ester was poured into a 125 ml Erlenmeyer flask containing 2.4 g of sodium methoxide, 40 ml of dimethylformamide (DMF) was added, the mixture was cooled to 0°, and a solution of 4.6 g (0.042 mol) of norcamphor in 5 ml of DMF was slowly dripped in. After standing at room temperature for

5 hr, the solution was diluted with 200 ml of a 1 :1 solution of ether and pentane and this mixture was washed with five 100-ml portions of water. Hie water washings were then extracted once with 100 ml of pentane and the combined organic phases were washed with saturated salt solution and dried over anhydrous magnesium sulfate. Hie solution was filtered, the solvents were removed on a rotary evaporator, and 159

~~the residue was distilled to yield 6.53 g (84.5$) of a 2 :1 mixture of~~

~~epimeric E- and Z-benzylidenenorbornanes (201 and 202), bp 78-80°~~

~~(0.15 Ena). These compounds were separated by preparative vpc on a 4 "~~

~~x 12’ 10$ FFAP on 4-5/60 Chrom W column at 150°, and were identical in~~

~~all respects to samples of 201 and 202 obtained from the reaction~~

~~of 2-chloromethylenenorbornane (199) with phenyllithium.~~

~~(8 3 ) L. F. Fieser, Organic Experiments, 2nd Ed., p. 121, Raytheon Education Company, Lexington, Mass. (1968).~~

~~Reaction of 2-Chloromethylenenorbornafte (199) with Methyllithium. To~~

~~a solution of 7.-0 ml (l4.0 mmol) of 2.0 M methyllithium in ether at~~

~~0° was added 0.20 g (1.4 mmol) of 199. The solution was then refluxed~~

~~for 12 hr, poured carefully onto ice, and diluted with ether. The~~

~~layers were separated and the aqueous layer was further extracted~~

~~with three 25-ml portions of ether and 35 ml of pentane. The combined~~

~~organic extracts were washed with saturated salt solution and dried~~

~~over anhydrous magnesium sulfate. The solution was filtered, the~~

~~solvents were removed by distillation through a glass helices packed~~

~~column and the residue chromatographed on 60 g of Fisher basic alumina~~

~~(pentane) to yield 9° mg (53$) of a mixture of epimeric ethylidene- norbomanes (137) and 3 -methylbicyclo[3 .2.l]oct-2-ene (48) in the~~

~~ratio of 3:1 as determined by nmr. Because the broad vinyl absorp tion of ethylidene comes at the same location as that of the vinyl i6o~~

proton of 2 -methylbicyclo[3 .2.l]oct-2-ene (49), the presence of the latter compound could not be determined. Separation of these compounds by column chromatography or vpc was not able to be accomplished.

~~The mixture was identified by comparison of spectral data obtained by mixing authentic samples of 137 and 48.~~

~~Reaction of 2-Chloromethylenenorbornane (199) with n-Butyllithium~~

~~Followed by Quenching with Deuterium Oxide. The Reaction with 80 mg~~

~~of 19J3 was carried out as described~~

~~above except that after stirring~~

~~for 20 min, the solution was~~

~~cooled to 0°, diluted with dry~~

~~206 ether and 5 ml of deuterium oxide~~

was slowly added. The deuterium oxide layer was saturated with sodium chloride, and the layers were separated. Further work-up as described gave j 6 mg (82$) of the epimeric 2-(l-deuteriopentylidene)norbomanes (206). Deuterium content was 76$ by mass spectral analysis and ca. 9°^ di in vinyl position by nmr as Judged by relative integration of vinylic and aliphatic hydrogens. The spectral properties of 206 were similar to those described for 200, except that the intensity of the olefinic region of the nmr was greatly diminished, and a weak C-D stretch was ob served at 4.52 |x in the ir. l6l

~~Control Reaction of 2-Pentylidenenorbornane (200) with n-Butyllithium~~

Followed hy Deuterium Oxide Quenching. A 100-mg sample of 200 was subjected to the reaction conditions described above for the reaction of 2-chloromethylenenorbornane (199) with n-butyllithium followed by quenching with d e u t e r i u m oxide. Work-up and chromatography gave 85

~~Mg (85$) of recovered 200, which showed a maximum of 3 . &$> deuterium incorporation by mass spectral analysis.~~

~~Reaction of 2-Chloromethylenenorbornene (lg2) with Ehenyllithium and~~

~~Methyllithium Followed by Deuterium Oxide Quenching. Solutions of phenyllithium and methyllithium in tetrahydrofuran were reacted with~~

199 under nitrogen as described above. The solutions were cooled, quenched with deuterium oxide, and worked up and described to give products identical to those observed when the reactions were quenched by pouring onto ice. A maximum of 2J& deuterium incorporation was observed by mass spectral analysis for both reactions. I

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~~2. M. Rei and H. C. Brown, ibid., 88, 5335 (1966); J. A. Berson, et.al., ibid., 89, 2590 (1967), and references therein.~~

3* P- G. Gassman, J. P. Andrews, Jr., and D. S. Patton, Chem. Commun., 437 (1969)*

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6. For reviews outlining the preparation, structure, and reactivity of organolithiums see: (a) R. J. Jones and H. Gilman, Organic Reactions, 6, 339 (1951); (b) H. Gilman and J. W. Morton, Jr., ibid., 87 258 (1954); (c) J. M. Mollan and R. L. Bebb, Chem. Rev., 69, 693 (1969); (d) T. L. Brown, Adv. Organometal. Chem., 3, 365~Xl965); (e) C. E. Coates, M. L. H. Green, and K. Wade, ''Organometallic Compounds,1' Vol. I, 3rd ed., Metheun and Co., LTD, London, 1967*

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8. (a) For an excellent review see: H. R. Ward, R. L. Lawler, and R. A. Cooper in Chap. 7 of ''Chemically Induced Magnetic Polarization,'' A. R. Lepley and G. L. Closs, Eds., John Wiley and Sons, New York (1973); (b) R. M. Magid, E. C. Nieh, and R. D. Gandour, J. Org. Chem., 3 6 , 2099 (1971); (c) R. M. Magid and E. C. Nieh,~fbid., 5 6, 2105 (1971)*

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~~1 6 2 163~~

~~11. S. J. Cristol and R. F. Helmreich, ibid., 77, 5034 (1955).~~

~~12. D. Y. Curtin, E. W. Flynn, and R. F. Nystrom, ibid., 80 , 4599 (1958); See also, D. Y. Curtin, J. A. Kampmeier, and B. R. O'Connor, ibid., 87, 863 (1965).~~

~~13. W. Kirmse, ''Carbene Chemistry,’' 2nd ed., pp 96-IO8 and 236-240, Academic Press, New York, 1971; G. Kobrich, Bull. Soc. Chim. France, 2712 (1962).~~

14. (a) G. L. Closs and R. A. Moss, J. Amer. Chem. Soc. , 86, 4042 (1964); (b) For the intramolecular reaction of an alkenyl substituted carbenoid see: G. L. Closs and L. E. Closs, ibid., 85, 99 (1963).

~~15. W. R. Moore, H. R. Ward, and R. F. Merritt, ibid., 8 3 , 2019 (1961); L. Skatteb^l, Tetrahedron Lett., 2361 (1970J; W. R. Moore, K. G. Taylor, and P. Muller, ibid., 2365 (1970).~~

~~16. (a) K. Ziegler and H.-G. Gellert, Justus Liebigs Ann. Chem., 567, 195 (see also pp 179 and 185) (1950); (b) P. D. Bartlett, S. Friedman, and M. Stiles, J. Amer. Chem. Soc. , 75, 1771 (1953).~~

IT. K. Ziegler, F. Dersch, and H. Wollthan, Justus Liebigs Ann. Chem., 511, 13 (1934); K. Ziegler, H. Wollthan, and A. Weriz, ibid., 511? 64 (1934); E. Grovenstein, Jr., and G. Wentworth, J. Amer. Chem. Soc. , 89, 1852 (1967); A. V. Tobolsky, J. Polymer Sci., 25, 2451 (1957).

~~18. (a) G. Wittig and C. Hahn, Angew. Chem. , 72, 781 (i960); (b) G. Wittig and J. Otten, Tetrahedron Lett., 601 (1963).~~

~~19. J. K. Crandall and A. C. Clark, ibid., 325 (1969). 2 0 . C. W. Jefford, J. Gunsher, D. T. Hill, P. Brun, J. Legros, and B. Waegell, Org. Synthesis, 51, 60 (1971).~~

~~21. Ventron (Alfa) Inorganics, Inc., 2.2-2.4 M n-butyllithium in hexane; 1. 4-2.2 M phenyllithium in 70:30 benzene-ether; 1.9-2.2 M methyllithium in ether.~~

22. For a discussion of the stability of organolithiums in tetrahydrofuran see H. Gilman and B. J. GaJ, J. Org. Chem., 22, II65 (1957). In practice, while substantial reductions in activity are seen at long retention times in tetrahydrofuran with all three organolithiums, in general reactions with the vinyl chlorides mentioned was rapid enough so that this was not a great problem. 164

~~23. L. K. Montgomery, F. Scardiglia, and J. D. Roberts, J. Amer. Chem. Soc., 87; 1917 (1965).~~

24. (a) L. K. Montgomery and L. E. Applegate, ibid., 89, 2952 (1967);,(b) L. K. Montgomery, A. 0. Clouse, A. M. Crelier, and L. E. Applegate, ibid., 89, 3^53 (1967); (c) see also L. K. Montgomery and L. E. Applegate, ibid., 89, 5305 (1967).

25. (a) R. W. Hoffman, '’Dehydrobenzene and Cycloalkynes,’’ Academic Press, New York, 1967; (b) '’Chemistry of Acetylenes,'' H. G. Viehe, ed., Marcel Dekker, New York, 1969; (c) J. C. Martin and Daniel R. Bloch, J. Amer. Chem. Soc., 93, 451 (1971); (d) G. Wittig and H. Hega, Ber., 9T, 1609 (1964T.

26. (a) G. Wittig and E. R. Wilson, Ber., 98; 451 (1965); (b) G. Wittig, J. Weinlich, and E. R. Wilson, ibid., 98, 438 (1965); (c) G. Wittig and J. Weinlich, ibid., 98, 471 T1965); (d) G. Wittig and P. Fritze, Angew. Chem. Internat. Edit., 5_, 846 (1966); (e) For evidence of cyclohexyne as an intermediate in the n-butyllithium reaction of 1-fluoroeyclohexene see: G. Wittig and U. Mayer, Ber., 96, 329 (1963); (f) G. Wittig, Angew. Chem. Internat. Edit., 1; 415 (1962).

27. (a) P. K. Freeman and T. A. Hardy, Tetrahedron Lett. , 3317 (1973); (h) A. T. Bottini and B. Anderson, ibid., 3321 (1973); (c) P. Monhanakrishnan, S. R. Tayal, R. Vardyanathaswamy, and D. Devaprabhakara, ibid., 2871 (1972); (d) J. J. Brunet, B. Fixari, and P. Caubere, Tetrahedron, 30, 2931 (197^)*

~~28. (a) P. West and R. Waack, J. Amer. Chem. Soc., 89, 4395 (1967); (b) R. Waack and M. A. Doran, ibid., 91? 2k^6 (1969); (c) P. West, R. Waack, and J. I. Purmort, ibid., 92, 840 (1970).~~

~~29. See ref. 19, and references described therein.~~

~~30. J. Wolinsky, J. Org. Chem., 26, 704 (1961).~~

31. H. Shechter, personal communication to P. G. Gassman; W. E. Slack, C. G. Moseley, K. A. Gould, and H. Shechter, J.Amer. Chem. Soc., 96, 7596 (1974); See also: J. W. Wilt and W. J. Wagner, J. Org. Chem., 29, 2788 (1964); A. P. Krapcho and R. Donn, ibid., 30; 641 (19S5); See ref. 13 for a discussion of the relative reactivity and selectivity of carbenes and carbenoids.

~~32. It also appears that methyllithium may react with 2-chloronorbomene (4) to produce I, X = CH3 by a coupling mechanism. 165~~

33* This is a common reaction of this type of bicyclic carbene. For example, see ref. 13, PP 247-250; J. Bredt and W. Holz, J. Prakt. Chem. , 203, 133 (1917); A. Angeli, Gazz. Chim. Ital., 24, II, 31 TT 1894); J. W. Powell and M. C. Whiting, Tetrahedron, 7, 305 (1959)j P. Clarke, M. C. Whiting, G. Papenmeier, and W. Reusch, J. Org. Chem., 27, 3356 (1962); J. H. Hammons, E. K. Probasco, L. A. Sanders, and E. J. Whalen, ibid., 33, 4493 (1968).

~~34. See ref. 13, pp 236-240; W. Kirmse and B. Von Biilow, Justus Liebigs Ann. Chem, , 666, 1 (1963).~~

35* (a) A. Russell in ''Technique of Organic Chemistry,’' Vol. VIII, Part I, A. Weissberger, ed., Interscience Publishers, Inc., New York, N. Y., 1961, p 343; (b) L. Melander, 1'Isotope Effects on Reaction Rates,'' The Ronald Press Co., New York, N.Y., i960, Chap. 2; (c) For a discussion of transition state structure in elimination reactions see: G. Biale, A. J. Parker, I. D. R. Stevens, J. Takahashi, and S. Winstein, J. Amer. Chem. Soc. , 94, 2235 (1972); (d) F. H. Westheimer, Chem. Rev., 61, 265 (19S2 ); (e) V. J. Shiner and M. L. Smith, J. Amer. Chem. Soc., 83 , 593 (l96l); (f) L. Funderburk and E. S. Lewis, ibid., 2531 (1964).

~~36 . (a) R. N. McDonald and R. N. Steppel, J. Amer. Chem. Soc., 92, 5664 (1970). (b) A sample of 115 was kindly provided by Dr. T. J. Atkins.~~

~~37. H. C. Brown, N. R. Aygangar, and G. Zweifel, J. Amer. Chem. Soc., 86, 397 (1964).~~

~~3 8 . R. Ratcliffe and R. Rodehorst, J. Org. Chem., 35, 4000 (1970).~~

~~39* K. Mislow and J. G. Berger, J. Amer. Chem. Soc. , 84, 7956 (1962); J. A. Berson, R. G. Bergman, J. H. Hammons, and A. W. McRowe, ibid. , 89, 2581 (1967).~~

~~40. (a) R. C. DeSelms and C. M. Combs, J. Org. Chem., 28, 2206 (1963); (b) E. Bergman, ibid. , 28, 2210 (1963); (cTl. Ghosez and P. Laroche, Proc. Chem. Soc., 90 (1963).~~

~~41. Attempted hydrogenation of 133 gave preferential hydrogenolysis to give 3-chlorobicyclooctane.~~

~~42. Use of methyllithium was unsatisfactory, presumably due to exporide formation and further reaction.~~

~~43. A. J. Sisti, J. Org. Chem., 35, 2670 (1970). 166~~

~~44. Product mixtures from 1^1^and 132 were similar, but not identical for each organolithium.~~

45. A variety of other bases were tried, including potassium t- butoxide in various solvents (no reaction or over reaction), exotic and common amines (no reaction), and methoxide and ethoxide (substantial amounts of alhyl ether formation). A strong enough base to abstract a hindered proton to effect a cis-elimination is needed. Thanks are extended to Mr. W. Pike for the idea of this method of synthesizing 143.

~~46. (a) J. Furukawa, N. Kawabata, and J. Nishiraura, Tetrahedron, 24, 53 (19^8)', (b) J. Nishimura, N. Kawabata, and J. Furukawa, ibid. , 25, 264? (1969).~~

4j. (a) For 158 and 159 see Y. S. Shabarov, T. P. Surikova, and R. Y. Levina, Zh. Org. Khimii, Vol. 1, No. 10, 1895 (1965)9 (b) For 154 and 159, see S. I. Khromov, G. P. Kochnova, 0. I. Guseva, and E. S. Balenkova, Neftek himiya, 6, 809 (1966).

~~48. The synthetic utility of allylic anions fqrmed using n-butyllithium and TMEDA has recently been explored. R. J. Crawford, W. F. Erman, and C. D. Broaddus, J. Amer. Chem. Soc., 94 , 4298 (1972).~~

49. (a) G. L. Closs and L. E. Closs, J. Amer. Chem. Soc. , 85, 99 (1963) and references to earlier papers therein; (b) G. L Closs, L. E. Closs, and W. A. Boll, ibid., 85, 3796 (1963); (c) H. Durr, Ber., 103, 369 (1970).

50. G. L. Closs, W. A. Boll, H. Heyn, and V. Dev, J. Amer. Chem. Soc.., 90,. 173 (1973)*

~~51. D. R. Morton, E. Lee-Ruff, R. M. Southam, and N. J. Turro, ibid., £2, 4349 (1970).~~

~~52. L. A. Paquette and S. E. Wilson, J. Org. Chem., 37? 3849 (1972).~~

~~53* R* E. Ireland and G. Pfister, Tetrahedron Lett., 2145 (1969)? R. E. Ireland, D. C. Muchmore, and U. Hengartner, J. Amer. Chem. Soc., £4> 5098 (1972).~~

~~54. A. T. Bottini, R. P. Carson, R. Fitzgerald, and K. A. Frost, II, Tetrahedron, 28, 4883 (1972).~~

55* B. L. Erusalimskii, et.al., Dokl. Akad. Nauk. SSSR, 169, 114 (1966), and references therein; B. L. Erusalimskii, I. G. Krasnosel*skaya, and V. V. Mazurek, Vysokomolekul Soedin., 6, 1294 (1964). ~ 167

~~56. (a) M. Schlosser and V. Landeriberger, Ber., 100, 5901 (1967); (b) E. J. Corey and R. A. Ruden, Tetrahedron Lett., 1495 (1973)? (c) G. Kobrich, Angew. Chem. Internat. Edit., 1, 51 (1962).~~

~~57* J* Wolinsky, J. Org. Chem., 26, 704 (1961).~~

~~58. K. L. Erickson, B. E. Vanderwaart, and J. Wolinsky, Chem. Common., 1031 (1968).~~

~~59* D. Seyferth, S. 0. Grim, and T. 0. Reed, J. Aner. Chem. Soc., 83 , 1617 (1961).~~

~~60. (a) G. Kobrich and H. R. Merkle, Ber., 99, 1782 (1966); (b) G. Kobrich and W. Goyert, Tetrahedron, 4327 (1968).~~

~~61. (a) G. Kobrich and R. Aisari, Ber., 100, 2011 (1967); (b) D. Y. Curtin and W. H. Richardson, J. Amer. Chem. Soc., 8l, 4719 (1959); (c) H. Gunther and A. A. Bothner-By, Ber., 9 6; 3112 (1963).~~

~~62. For a general study of the reaction of alkyllithiums with aldehydes and ketones see: J. D. Buhler, J. Org. Chem., 38 , 904 (1973).~~

~~63 . C. W. Jefford and E. H. Yen, Tetrahedron, 4549 (1967).~~

~~6k. C. W. Jefford, A, Sweeney, and R. Delay, Helv. Chim. Acta, 55, 2214 (1972).~~

~~65. W. Kraus and R. Dewald, Justus Liebigs Ann. Chem., 689, 21 (1965). A detailed examination of the stereochemistry of 52 and 53? and the details of dehydration are presented.~~

~~66. D. G. Farnum and G. Mehta, J. Amer. Chem. Soc., 91? 3256 (1969).~~

~~67. H. 0. House and G. H. Rosmusson, J. Org. Chem., 26, 4278 (1961).~~

~~68. N. A. Belikova, et.al., Zh. Org. Khimii, 1, 506 (1965).~~

~~69. C. W. Jefford, et.al., Chem. Commun., 310 (1967); Jefford reports exo addition of dichlorocarbene to bicyclo[3*2.l]oct-2- ene and states that the resulting dichloride opens only above 200°.~~

~~70. For ir data of 152 see: C. Altona, H. J. Hageman, and E. Havinga, Spectrochimica Acta, 2kA, 633 (1968).~~

~~71. M. Mousseron and R. Jaquier, Bull. Soc. Chim. Fr., 648 (1950).,~~

~~1 1 6 8~~

~~72. A. N. Volkov, A. V. Bogdanova, and G. P. Kugatova- Shemyakina, Zh. Org. Khimii, Vol. 3, No. 2, 316 (1967).~~

~~73. T. G. Selin and R. West, J. Amer. Chem. Soc., 84, 1863 (1962).~~

~~7^. For an ir of 2l8, see ref. 70.~~

~~75• H. Suhr, et.al., Justus Liebigs Ann. Chem., 649, 53 (1961).~~

~~76. Satler IR No. 24291.~~

~~77. G. Stork and S. R. Dowd, J. Amer. Chem. Soc., 8 5, 2178 (1963).~~

~~78. E. Warnoff, D. G. Martin, and W. S. Johnson, Org. Syntheses, Coll. Vol. 4, 162 (1963).~~

~~79* K. G. Taylor, W. E. Hobbs, M. S. Clark, and J. Chaney, J. Org. Chem., 37; 2k36 (1972).~~

~~80. E. J. Corey and J. G. Welch, J. Amer. Chem. Soc., 88, 5736 (1965).~~

~~81. V. T. Aleksanyan, et. al., Izvest. Akad. Nauk S.S.S.R. , Otdel. Khim. Nauk., 84 (i960). This reference contains a discussion of the dehydration of 1,2-dialkylcyclohexanols.~~

~~82. L. A. Paquette, B. A. Johnson, and F. M. Hinga, Org. Syntheses, Coll. Vol. 5, 215 (1972).~~

~~83 . L. F. Fieser, Organic Experiments, 2nd Ed., p. 121, Raytheon Education Company, Lexington, Mass. (1968).~~