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5. PLEASE NOTE: Some pages may have indistinct print. Filmed as received. Xarox University Microfilms 300 North ZMbRMd Ann Arbor, Michigan 4S100 PRESS, J e ff e r y B ruce, 191*7- SYNTHESIS AND CHEMISTRY OF BICYCL0[4.2 .2]DECA- 2,H,9-TRIEN-7-ONE AND BICYCL0[«+.2.2;)DECA- 2,h,9-TRIEN-7-YL INTERMEDIATES.

The Ohio State University, Ph.D., 1973 Chemistry, organic

University Microfilms. A XEROX C o m pany # Ann Arbor. Michigan j

THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED. SYNTHESIS AND CHEMISTRY OP BICYCL0[4.2.2]DECA-2,lf;9-®IEN-7-0NE AND

BICYCLOL^.2.2'JDECA-2A;9-TRIEN-7-YL INTERMEDIATES

DISSERTATION

Presented In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio S ta te U niversity

Jeffery Bruce Press, B.S. # * * * *

The Ohio S ta te U niversity

1973

Reading Conmittee; Approved hy

Dr. Harold Shecbter

Dr. Paul Gassman

Dr. Robert Ouellette Adviser Department of Chemistry DEDICATION

To my parents

11 ACKNOWLEDGMENT

The author is grateful to Dr. Harold Shechter for suggestion of this problem, for his ever-present enthusiasm and Imaginative guidance and for his aid in preparing this manuscript. Dr. Shechter's wit, imagination, and knowledge provided stimulation and encouragement during the course of study.

The author is indebted to Messrs. Gary Blrriberg and J. Michael

Geckle and Dr. Paul Gassman for enlightening discussions concerning exper imental results. He is further indebted to Mr. Geckle for both measure ment and Interpretation of nmr data which was essential for completion of this work and to Miss Carol Rose for her skill and patience in typing and illustrating the final manuscript. The author also wishes to acknow ledge interesting discussions of both chemical and non-chemical nature with Messrs. Blrnberg, Geckle, Roger Drewes, and Gordon Gruetzmacher at local pubs in Columbus.

The author must express deep appreciation to Fhilllpus Aureolus

Theophrastus Bombastus von Hohenhelm who provides the eternal light to alchemists everywhere and lastly to his wife, Debbie, whose many lonesome nights allowed completion of much of thiB work.

i l l VITA

May 2h, 1 9 k 7...... Born - Rochester, New York

1 9 ^ 9 ...... B.S. - BuckneU University, Lewishurg, Pennsylvania

1 96 9 -1 9 7 3 ...... Teaching Assistant, Department of Chemistry, The Ohio State Univer sity, Colunibus, Ohio

1973 ...... Research Associate, Department of Chemistry, The Ohio State Univer sity, Columbus, Ohio

PUBLICATIONS

'The Chemistry of Bicyclo[^.2.11nona-2,^,7-trien-9-one, Bicyclo(.U.2.1]- nona-2,4,7-trien-9-yl Intermediates and Their Derivatives," T. A, Antkowiak, D. C. Sanders, G. B. Trimitsis, J. B. Press, and H. S hechter, J . Amer. Chem. S o c., 9hj 3366 (1972).

“Facile Synthesis of Bicyclo[4.2.21deca-2,4,7>9-Tetraenes," J. B. Press and H. Shechter, Tet. Letters, 2677 (1972).

iv TABLE OF CONTENTS

Page

DEDICATION...... 11

ACKNOWLEDGMENTS ...... I l l

VITA...... lv

LIST OF TABLES...... x

STATEMENT OF PROBLEM...... I

HISTORICAL...... 2

RESULTS AND DISCUSSION...... IT

SUMMARY...... 77

EXPERIMENTAL...... 80

. General Procedures and Techniques ...... 60

Preparation of Biqyclo[4.2.1]nona-2,li,7-trien-9-one ...... 8 l

Reaction of Bieyclo[U.2.1]nona-2,lf,7-trien-9-one with Diazomethane ...... 6

Reaction of Bicyclo[^.2.2]deca-2,lt-,9-trien-7-one (l) with Semicarhazlde Hydrochloride ...... 82

Preparative Isolation of Bicyclo[lj-.2.23deca-2,U,9-trien- 7 -one ( l ) ...... 83

Reaction of Bicyclo£h.2.2]deca-2,lf,9-trien-7-one (l) with 2,l*-Dinitrophenylhydrazine ...... 7*...... 8^

Reaction of Bicydo[J|.2.2]deca-2,if,9,"trien-7-one (l) with Hydroxylamine H y d ro c h lo rid e ...... 8*f

Catalytic Hydrogenation of Bicyclo[i|. 2.2]deca-2,^,9-trien- 7 -o n e ( l ) ...... 83

V Page

Reaction of Bicyclo[4.2.2]decan-7-one (4) with 2,lf-Dinitro- phenylhydrazine ...... 7 ...... 65

Reaction of Bicyclo[l+.2.2]decan-7-one (U) with Semlcarbazide Hydrochloride ...... 66

Catalytic Hydrogenation of Bicyclo[U.2. l]nona-2,U,7-trien- 9 - o n e ...... -...... • . 86

Reaction of Bicyclo[U.2.1]nonan-9-one ( 6) with Diazomethane ... 87

Base-Catalyzed Mono- and Dideuteratlon of Blcyclo[U.2.2Jdeoa- 2 ,U,9 - tr ie n - 7-one ( l ) ...... 87

Reaction of Bicydo[U.2.2]deca-2,J+,9-trien-7-one (l) with * * Potassium t-Butoxlde and Deuterium O xide ...... 7 ...... 88

Reaction of Bicyclo[U.2.2]deca-2,4,9-trlen-7“One (l) with Potassium t-B u to x id e and Water in Dim ethylform aml'de...... 88

Reaction of Bicyclo[^.2.2]deea-2,4,9-trien-7-one (l) with ToBylhydrazlde ...... 7 ...... 89

Reaction of Bicyclo[^.2.2]deca-2,4,9**trien-7-one (l) with Benzenesulfonylhydrazide ...... 7 ...... 89

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one Tosylhydra- zone (12) with M ethylllthium ...... 90

Reaction of Bicydo[4.2.2]deca-2,4,9-trien-7-one (l) with Isopropenyl A cetate ...... 7 ...... 91

Reaction of Bicyclo[U.2.2]deca-2,l*,9-trien-7-one (l) with Potassium t-Butoxide and Acetyl Chloride in Glyme ...... 91

Reaction of 7-Acetoxybicyclo[if.2.2]deca-2,^,7j9-tetraene ( 15 ) with 3N Hydrochloric A cid ...... 92

Reaction of B icy do [4.2.2]deca-2, U, 9-trien-7-one (l) with Pyrrolidine ...... 7 ...... 92

Reaction of 7-Pyrrolidinobicyclo[l;.2.2]deca-2,U,7>9-tetraene (1 6) with 3N Hydrochloric A cid ...... 95

Reaction of Bicyclo[4.2.2]deca-2,U,9-trien-7-one (l) with Potassium t-Butoxlde and Methyl Fluorosulfonate Tn Hexa- methylphosphoramlde ...... 95

v i Page

Reaction of p-Tetralone with Potassium t-Butoxlde and Dimethyl Sulfate in Dimethylformamide” ...... 9k

Reaction of Bicyclo[U.2.2]deca-2,l|-,9-trien-7-one (l) with Potassium t-Butoxlde and Methyl Fluorosulfonate in Glyme .... 96

Reaction of 7-Methoxybicyclo[lf.2.2]deca-2,1^7>9“tetraene (17) with Hydrochloric A cid ...... •...... 98

Reaction of Blcyclo[^.2.2]deca-2,U,9-trien-7-one (l), with Potassium t-Butoxide and Trimethylsilyl Chloride"*in Glyme ... 99

Thermal Rearrangement of 7-Methoxybicyclo[^.2.2 ]d eca-2 ,7>9- tetraene (rf) ...... 99

Preparation of 2-Methoxynaphthalene ...... 100

Reaction of Bicyclo[U.2.2]deca-2,U,9-trlen-7-one (l) with Lead Tetraacetate ...... 7 ...... 101

Acid-Catalyzed Reaction of anti- 8-Acetoxyhicyclo[>+.2.2]- deca-2,U#9-trien-7-one (26) with Methanol ...... 101

Reaction of syn- 8-M ethoxybicyclo.2.2]deca-2,U,9-trien-7-one (28) w ith 2 ,4-Dinitrophenylhydrazine ...... 102

Attempted Acid-Catalyzed Hydrolysis of anti- 8-Acetoxyblcyclo- [4.2.2]deca-2,ll-,9"trien-7-one ( 2 6) in Dimethylformamide- W a te r...... 102

Reaction of Bicyclo[U.2.2]deca-2,lf,9-trien-7-one (l) with Isoanyl Nitrite and Potassium t-Butoxlde 7...... 103

Reaction of Bicydo[li-.2.2]deca-2,lf,9“'trien-7j8-dione Mono- oxlme (%£) with o-Fhenylenediamine ...... 103

Reaction of Bicyclo[if.2.2]deca-2,^,9-trien-7-one (l) with Sodium Methoxide and Methyl Form ate ...... 7 ...... 10^

Reaction of 8-FarnyIbicyclo[l*,2.2]deca-2,^,9-trien-7-one (3 8) with Hydrazine ...... 103

Reaction of 8-Formylbicyclo[^.2,2]deca-2,^,9-trien-7-one (3 8) with Tosyl Azide and Triethylamine ...... 103

Photolysis of 7-Diazdbicyclo[lf.2.2]deca-2,lj-,9-trien-8-one (37) in Water-Dioxane ...... 106

v i i Page

Reaction of BlcycloC^.2 .11nona-2,U^7-trlen-syn-9"carbojtylic Add (40) with Diazomethane ...... 107

Reaction of 7-Diazobicyclo[4. 2.2]deca-2, k,9-trien-8-on

Hydrolysis of endo-6-(els-2' -acetoxyvinyl)-cls-bieyelo- C5»5»°]octa-3j7-dien-2-one ...... 109

Catalytic Hydrogenation of exo-2-Acetoxybicyclo[5.2.l]*‘ deca-3i 5»8-trien-10-one (W) ...... 109 Reaction of exo-2-Acetoxyblcyclo[5.2. l]decan-10-one (gO) with Sodium Hydroxide in M ethanol-Vater ...... 110

Oxidation of exo-2-Rydroxybicyclof5.2. lldecan-10-one (gl) with Chromic A cid ...... I ...... H I

Reaction of 7-Diazobicyclo[4.2.23deca-2,4,9-trien-8-on« (37) with Hydrogen C hloride ...... 111

Catalytic Hydrogenation of exo-2-Chlorobicyclo[5.2.l]deca- 3 ,5 ,8 -trie n -lO -o n e (j>4) ...... j ...... 112

Reaction of Bicyclo[5.2.1]decan-10-one (5jj) with 2,U-dinitrophenylhydrazine ...... 113

Reaction of exo-2-Chlorobicyclo[5.2. 11deca-3i5.8-trien-lO-one (j§4) with Silver A cetate ...... 114

Attempted Wolff-Kishner Reduction of Bicyclo[4.2.2]deca- 2,4,9-trien-7-one (l) ...... 114

Reaction of Bicyclo[4.2,23deca-2,4#9-trlen-7-one (l) with Hydrazine ...... T.. 115

Reaction of Bicyclo[4,2.23deca-2,4,9-trien-7-one Hydra^one (6g_) with Tosyl C hloride ...... 115

Attempted Wolff •Kishner Reduction of Bicyclo[4. 2.2]decu- 2,4,9-trien~7-one Hydrazone (65) ...... 116

Attempted Wolff-Kishner Reduction of Bicyclo[4.2.2]deca- 2,4,9-trien-7**one Semicarbazone ( 3 ) ...... 116

Attempted Wolff-Kishner Reduction of BicycloCli. 2.2]deca- 2,l+,9-trien-7-one (l) using Benzoylhydrazide as a Source of Hydrazine In Situ ...... 117

v i i i Page

Reaction of Blcyclo[k.2.2]deca-2,k,9-trien-7-one (:l) v ith Methylhydrazine ...... 117

Reaction of Bicyclo[k.2.2]deca-2,k,9-trien-7-one (l) with Methylhydrazine and Potassium Hydroxide in Ethylene Glycol .. 117

Reaction of Bicyclo[k.2.2]deca-2,k,9-trlen-7-one (l) vith D im azin e ...... 7...... 116

Reaction of Bicyclo[k.2.2]deca-2,k,9-trien-7-one (l) with Bimazine and Potassium Hydroxide in Ethylene G lycol ...... 116

Reaction of Bicydo[^.2.2]deca-2,U/9-trien-7-one (l) with Sodium Borohydrlde ...... 77...... 119

Reaction of BicycloC^.2.2]deca-2,lf,9-trien-sjrn-7-ol (77) with Acetic Formic Anhydride ...... 120

Reaction of Bicyclo[k. 2.2]deca-2, k, 9-trlen-ayn-7-ol (77) vith Triphenylphosphine Dihromide in DimethylformamicTe 120

Irradiation of Bicydo[k.2.2]deca-2,k,9-trien-7-one (l) in A c eto n e ...... 7...... 121

Irradiation of Bicyclo[k.2.2]deca-2,k,9-trien-7-one (l) in E t h e r ...... 7...... 122

Irradiation of BicycloCk,2.2]deca-2,k,9-trien-7-one (l) with Michler's Ketone as Sensitizer ...... 7...... 122

Preparation of Barharalone ...... 12?

Reaction of Barhardone with Diazomethane ...... 12? Reaction of Tricydo[?.?. 2. 0a,6]deca-?#6-d ie n - 9 -one ( 8?) with Tosylhydrazide ...... 12?

Reaction of Tricyclo[5.?»2.Oa , 0]deca-?,6-dien-9-one ( 8?) vith Dilute Trifluoroacetic A cid ...... 12k

Reaction of Tricydo[?.?-2.0a, 8]deca-?,6-dien-9-one ( 8 3) vith Sodium Borohydrlde ...... 12k

APPENDIX I - IR AND NMR SPECTRA...... 126

lx LIST OF TABLES

Table P age

I Product Distribution from Reaction of Bicyclo[U.2.2]- deca-2,^,9-trlen-7-one (l) vith Potassium t-Butoxide and Methyl FluoroBulfonate in Polar Solvents .7 ...... 32

II Ntnr Data Observed for 7-Substituted BicycloCU,2.2]deca- 2,1*,7>9-Tetraenes lj^ IJ5, 16, and 2 1 ...... 36

III Nmr Data Reported for Substituted Bicyclo[^.2.2]deca- 2,1*,7>9-Tetraenes ...... 37

IV Double Irradiation of endo-6-(cls-2t - Acet oxyvinyl) - c is - b ic y c lo [ 3 -3 »0 ]o c ta - 3 #7-d ie n - 2-one (J 57 ) ...... 56

V Eu(Fod)a Induced Chemical Shift Data for Compound 6k 6l

VI Eu(Fod )3 Induced Chemical Shift Data for Compound 7 3 ,...... 67

VII Product Distribution from Reaction of Bicyclo[k. 2.2]deca- 2,k,9-trien-7-one (l) vith Potassium t-Butoxide and Methyl Fluarosuli’onaibe in Hexamethylphosphoramide ...... 93

VIII Product Distribution from Reaction of Bicyclo[k.2.2]deca- 2,l+,9-trien-7-one (l) vith Potassium t-Butoxide and Methyl Fluorosiilfonate in Glyme 7 ...... 97

x "I learned this at least, by ny experiment; that if one advances confidently in the direction of his dreams, and endeavors to live the life which he has imagined, he w ill meet with a success unexpected in common hours. In proportion as he simplifies his life, the lavs of the universe w ill appeal less com plex ... If you have built castles in the air, your work need not be lost; that is where they should be. Now put the foundations under them . n

Henry David Thoreau from Walden STATEMENT OF THE PROBLEM

Bicycloflf. 2.1]nona-2,^,7"trien-9-one is potentially useful for pre paring ring expanded bicyclic systems.

The present research involves synthesis and study of bicyclo[l 4-.2 . 2 ]-

deca-2 , ^ , 9 - t r ie n - 7-one (l) as derived by ring expansion of bicyclo[^. 2 . 1 ]-

nona-2,U,7-trien-9-one vith diazomethane. Ketone 1 is to be investigated

for preparing bicydo[lf. 2 . 21deca-2,Jf,7>9 -tetraene (3Jf) and 7-substituted bicyclo[lf.2.2]deca-2,lf,7*9-tetraenes. Photochemical reactions of ketone

iL are also of interest for synthesis of novel bl- and tricyclic ketones.

Functionalization of ketone !L at C -8 may allow preparation of bicydo-

[U.2.2]deca-2,4,9-trien-T>8-dione ( 5 6 ) and its derivatives. The properties

of bicyclo[l+.2.2]deca-2,U,9“trien-7-yl carbonium ion, carbene, carbanion

and radical as well as 8-ketobi cyclop. 2 . 2 ]deca-2, 4 ,9 - t r len - 7-yl carbene

and carbonium ion are to be investigated.

Expansion of the [4.2.23bicyclic system may provide a route to

synthesis of bicyclo[lf.5.2]undeca-2,4,8,10-tetraene-7-one. Study of the

generation and properties of the bicyclo^. 3 .2 ']undeca- 2 ,U,8, 10- te tr a e n -

7-yl carbene, carbonium ion and radical is proposed in attempts to study possible blcycloaromaticity and stability of such species. HISTORICAL

Hydrocarbons on the (CH)io energy surface are of intense interest because of their facile photochemical and thermal Interconversions. These

Isom erization re a c tio n s provide extrem ely stro n g support fo r th e Woodward- x Hoffmann selection rules. Since Nenitzecsu reported the first hydrocarbon

(l) H. B. Woodward and R. Hoffmann, f

2 lying on this energy surface in I 960, numerous publications concerning the preparation, isomerization, and chemistry of various (CK)io compounds have 3 appeared.

(2) M. Avram, E. Sliam, and C. D. Nenitzecsu, Ann., 636, 18^ (i960).

(3) For reviews of work in this area see: (a) T. L. Burkoth and E. E. van Tamelen, Chapter 3 of "Noribenzenoid Aromatics,” Vol. 1, J. P. Snyder, Ed., Academic Press, New York, N. Y. (1969)l and (b) L. T. Scott and M. Jones, Jr., Chem. Rev., 72, l 8l (1972).

Scott and Jones prepared and characterized the (CH)io hydrocarbon, b ic y c lo lU . 2 . 21d eca-2,U,7 , 9-tetraene, as the major product (37.87) of ther mal decomposition of the sodium salt of 9*formylbicydo[6.1.03nona-2,4,6- trlene tosylhydrazone. Other products include els- and trans-9,10-dihydronaphthalenes ( 1 1 .6 7 and 207, respectively), cyclooctatetraene ( 12 . 7 7)#

2 3 ,U-dihydronaphthalene ( 1 3 . yf>), cis-l-phenylbutadiene (k.6%), and naphtha- 4 5 lene (l$) (Equation l). The decomposition process has been presumed to

(^ ) M. Jones, J r . , and L. T. S c o tt, J . Amer. Chem. S o c ., 8 150 (1967).

(5) M. Jones, Jr., S. I>. Reich, and L. T. Scott, ibid., £2, 3118 (19T0).

Ha® 0 -NTs 90-120 CK \ +

(1)

00 * 00 * 0*00

involve carbene generation followed by cleavage to a diradical which in

turn recombines to form products (Equation 2). Bicyclo[U.2.23deca-2,lf,7,9-tetraene has also "been prepared "by photo

chemical rearrangement of cls- 9 . 10-dlhydronaphthalene followed hy thermal 6 , 7 ,8 opening, Irradiation of els- or trans-9> 10-dlhydronaphthalene as well

(6 ) W. von E. Doering and J. W. Rosenthal, Ibid., 88, 2078 (1986).

(7) W. von E. Doering and J. W. Rosenthal, Tet. Letters, 3^9 (1967)*

(8 ) M. Jones, J r .# J . Amer. Chem. S o c., 8ft, 1*236 ( 1967).

as bicyclo[ 6. 2 , 0 ]deca-2 , ^ , 6, 9 -tetraene produces the same ratio of products, 2 IO S T namely thermally unstable tetracyclo[l*.l*. 0 ,0 1 .0 * 3deca”3 , 8-dlene ( 65%), tr a n s - 9 , 10-dlhydronaphthalene ( 20%), c ls - 9 . 10-dlhydronaphthalene ( 8%), and 9 bullvalene (7%) (Equation 3)* The tetracyclic hydrocarbon opens via

(9 ) S. Masamune, R. T. Seidner, H. Zenda, M. Wiesel, N. Nakatsuka, and G. Bigam, Ibid., 90, 5286 (1968). a thermally allowed *w 2 process to produce bicyclo[^. 2 . 2 ]deca-2,U,7, 9- tetraene# opening to d s“ 9 »10-dlhydronaphthalene in a h+ 1* reaction Is not

thermally allowed and Is not observed (Equation U),

Catalytic Isomerization of bullvalene also produces the bicyclic[lf.2.2]- tetraene. Thus mercuric or zinc halides produce bicyeloC^.S^deca-S,!^^" / 10 te tra e n e ( 987") along w ith c l s - 9 , 10-dihydronaphthalene and naphthalene.

(10) H. P. Loffler and G. Schroder, Angew. Chera. Int. Ed., Jj 736 (1968).

Similar rearrangement (60Jb yield of the desired tetraene) also occurs upon 11 use of bis(benzonitrilo)palladium chloride. Substituted bullvalenes give xo the corresponding tetraenes (Equation 5)* Fluorobullvalene rearranges

( l l ) E. Vedejs, J . Amer. Chem. S op., 90, U751 (1968) 6

(5 )

R b Hf -CH3, -CQ2CH3

to two tetraenes, one with fluorine at the 7 - position and the other with

. the substituent at the 1- position.

Many and 7>8-disubstituted bicydot4.2.2]deca-2,4,7,9-tetraenes

have been prepared by photochemical rearrangement of appropriately disub- l a - i e s t i t u t e d c1b- 9 , 10-dihydronaphthalenea (Equation 6 ). Profound changes

(12) W. Grimme, H. J . R ie b e l, and E. V ogel, Angew. Chem. I n t . E d ., 7, 823 • (1968).

(13) J. S. McConaghy, Jr., and J. J. Bloomfield, Tet. Letters, 1121 ( 1969).

(14) J. Altman, E. Babad, M. B. Rubin, and D. GinBburg, ibid., 1125 (1969).

(15) J. Altman, E. Babad, D. Ginsburg, and M. B. Rubin, Isr. J. Chem., 7, 435 (1969).

(16 ) W. von Philipsborn, J. Altman, E. Babad, J. J. Bloomfield, D. G in B - b u rg , and M. B. Rubin, H elv. Chim. A c ta , 53? 725 (1976). in the product are caused by slight substituent modifications; isomeriza tion via thermally allowed internal forward and reverse Diels-Alder reac tions accounts for these results (Equation 7). Adequate explanations for these substituent effects have not yet been advanced.

I II III

Product Form Ri* Ra (isom er ♦) -C0aCH3 I -CO-X-CO- (X - 0- , -NH-, III -NCH3- ) -CHaOCHa— III —CHgOCO— I, II, III mixture

Some 7,8-dlsubstitubed bicyclo[4.2.2]deca-2,4,7,9-tetraenes are formed in modest yields by reaction of disubstituted acetylenes vith tricarbonyl- 17 cyclooctatetraeneiron (Equation 8 ). Most acetylenes trimerize under the reaction conditions.

(IT) U. Kruerke, Angew. Chem. Int. Ed., 6, 79 (1967). 8

R I + in (8) Pe(CO)3 6 R o phenyl, -CO 2CH3, -Si(CHa)3

Photochemical rearrangements of 9>10-disubBtituted bicyclo[ 6. 2 .0]deca-

2 , ^ , 6, 9 -tetraenes also give bicyclop+. 2 . 2 ]deca-2, k, 7, 9-tetraenyl derivatives, 9 Besides the parent system described earlier, 9-chloro-lO-fluorobicyclo- le [6.2.0]deca-2,4,6,9-tetraene (Equation 9) has been rearranged vith light.

( 18) H. Rottele, P. Hikoloff, J. F. M. Oth, and 0. Schroder, Chem. Ber., 102, 5367 (1969).

(9)

F n i 18 A possible reaction mechanism Involves photochemically allowed disrota- « * tory ring opening to an a ll cis-cyclodecapentaene and thermally allowed

conrotatory ring closure to the appropriately substituted eis- 9 , 1 0 -d ih y d ro -

naphthalene which then reacts further as previously discussed (Equation 10).

d is con CX ( 1 0 ) C l

B icy clo[4.2.2]deca-2,4,7>9-tetraene and its derivatives iBOmerize thermally and photochemically. 7-Deuterio[4.2,2]deca-2,4,7>9-tetraene as prepared from deuterated 9-fornylbicyclo[6.1.0]aeca-2,4,6-triene undergoes 19 12,20 deuterium scrambling; similar observations have been made on the

(19) M. Jones, Jr., and B. Fair less, Tet. Letters, 4881 ( 1968).

(20) R. T. Beidner, N. Hakatsuka, and S. Masamune, Can. J. Chem., 48, 187 (1970).

7,8-dideuterio derivative (Equation ll). The Isomeric distribution of 10 deuterium is statistical) 66^ of the deuterium is on the monoene bridge vhile 33/6 1b on the 3~ emd ^-positions. This isomerization is strictly analogous to the previously described for bicyclo[U. 2 . 2 "1deca-2, 7>9 - t e t r a - enyl systems via internal 4+2 cycloadditlon and ring opening (Equation ?).

Thermal rearrangements of bicyclol4.2.2ndeca-2,4,7*9-tetraenes also lead to substituted cls-9»10-dihydronaphthalenes. Thus, cis-9»10-dihydronaphthalene ( 20#) and naphthalene (80#) are produced from the parent 7 tetraene (Equation 12). Similarly, deuterium is Incorporated on C-2, 3>

A (1 2 )

5 4

6, and 7 (1*2 D) and 0 9 and 10 (0 .6 D) upon starting vith 7>8-dideuterio- 20 bicyclo[4.2.2]deca-2,4,7*9**tetraene. Likewise the 7> 8-diphenyl derivative 17 thermolyzes mainly to 2, 3-diphenylnaphthalene (Equation 13). A reasonable

interpretation of these conversions to naphthalenes involves intramolecular

Diels-Alder reactions followed by disallowed 4+4 ring openings to produce dihydronaphthalenes. Subsequent loss of hydrogen leads to the fully aro matic products (Equation lh).

(1*0

Bicyclo[lj-.2.2]deca-2,l*,7j9"tetraenes may also be isomerized photo- 5 chemically. Irradiation of the parent hydrocarbon produces bullvalene ' possibly via a di-n-methane rearrangement 2 (Equation 15). Substituted

(21) H. E. Zimmerman and A. C. P r a t t, J . Amer. Chem. S oc., 92, 6267 (1970) and references contained therein.

bullvalenes have been prepared similarly. Thus Irradiation of 7>8-diphenyl- IV b icyclo[U. 2.2]deca-2, U, 7,9“tetraene yields diphenylbullvalene. Chloro- xa fluorobullvalene has been prepared analogously. t Bicyclo[l*.2.2]deca-2,l*,7>9-tetraenes are electron-rich and exhibit marked reactivity with electrophilic reagents. Reaction of the parent hydro- .1 2

-V

(15)

carbon vith superacid leads to preparation of the bicyclo[ 4 .3 . 1 ]deca- 2 2 »2 3 2,4,7-trienyl cation (Equation 16). Addition of other electrophiles

H ^ H

FS03H- SQaClF -128

(1 6 ) 13

(22) M. Roberts, H. Hamberger, and S. Winstein, Ibid., §2, 6}b6 (19T0).

(23) G. Schrc&er, U. Frange, B. Futze, J. Thio, and J. F. M. Oth, Chem. Ber., lOfr, 3^06 (1971).

vlth subsequent quenching by a counter-Ion produces various mono- and dl- 2 3 substituted bioyclot>l|'.3.11deca-2,U,8-trienes (Equation IT).

E,© v (17)

-E-A

-HgX -OCH3 -Br ■Br -H ■Br

Electrophilic addition to 7-eubstituted tetraenes theoretically can produce four Isomers (Equation l 8 )j product is o la tio n however show* 24 that the reactions proceed with large electronic control. With the 7~*

(2lf) g. Schroder* U. Prange, and J. F. M. Oth, Chem. Ber., 105, 185^ (1972).

bromo- and 7-acetyl derivatives, reaction with fluorosulfonic acid fol lowed by quenching with methanol-sodium carbonate provides products resulting from reaction paths l 8c and d (Equation 19). With the 7-methyl-

OCH3 1) FSO3H >> R (19) 2) CH3OH R

R c -B r, _COOCH3

24 tetraene, reaction occurs exclusively via path 18a (Equation 20).

(2 0 )

CH3

Chlcr osulfonyl isocyanate has Been reacted vith a variety of siibstl- tuted bicyclo[4.2.23deca-2,U,7*9-tetraenes. With 7-monosubstituted tetraenes, isomeric products result from addition of the uniparticulate bipolar 25 electrophile (Equation 21). For 7*8-disubstituted tetraenes, various

(25) L. A. Paquette and M, J, Broadhurst, J. Org. Chem., % 8 , 1886 (1973)* 16 results occur (Equation 22). When 7-methoxy-8-methyltetraene (Ri = -OCH 3,

( 22) IV VI

R2 « -CH3 ) reacts, a mixture of isomers IV and V results, vhereas the 7,8- 2 4 diphenyl derivative forms isomer VI exclusively.

The above products are postulated to he produced by 1,2-cycloaddition to form {3-lactams, ring opening to zvitterlonic bishomobropylium ions, and closure to products (Equation 23)*

OaCl ClS0aN=C»0

(2 3 )

Products RESULTS AND DISCUSSION

The synthesis, chemistry, and synthetic u tility of b i cyclop. 2.2 Jde ca-

2,^,9-trien-T-one and its derivatives have presently been investigated.

Facile synthesis of this system is made possible by the earlier preparation

( 26) T. A. Antkowiak, Ph.D. Dissertation, The Ohio State University, Columbus, Ohio (1968).

in this laboratory of bicyclo^. 2 . l]n o n a- 2,U, 7- t r ie n - 9-one in high yield from cyclooctatetraene dianion and dimethylcarbamoyl chloride (Equation 2I4-).

0 II + (CHaJaNCCl

Bicyclo[l*.2.2]deca-2,lf,9-trien-7-one reacts vith excess diazomethane o 2 7 in methanol-chloroform-ether at 0° vith lithium chloride catalyst to

(27) A modification of the method of M. Stoll and W. Scherrer, Helv. Chim. Acta, 23, 9^1 ( 191*0 ).

give bicyclo[4.2.2]deca-2,U,9-trien-7-one (l, 50 - 85^) and spiro[bicyclo- Ifl

[U.2.13nona-2,lf,7-trien-9j2,-oxirane3 (2^ 15-50?) (Equation 25). Isomers

CHs N2 -n 2 3 + \\ (25) 10 5

1 and 2 may "be separated by preparative gle. The structure of 1 is esta blished by its combustion analysis and spectral properties including infrared absorption at 1700 cm_1j ultraviolet absorption maxima in ethanol at ltT^y

202, 258 , 265 * and 300 nm (e « ^250 , 3070, 2920, and 373 )j nmr ab so rp tio n s a t 8 5 .9 (m, 6H, H at C-2, -3, -U, - 5 , -9, -10), 3-5 (m, IK, H at C- 6),

3.0 (m, 1H, H at C-l), and 2.55 (d vith a, 2H, H at C- 8)j and mass spec tral absorption, m/e = 1 k6, for its parent ion. Ketone 1 further forms the expected semicarbazone ( 3, rap 199* 5 “200. 5 °), oxime (mp 131- 132° ) , and 28 2,U-dinitrophenylhydrazone (rap 221- 222.5 ) derivatives of proper combus tion analysis.

(28) Carbonyl derivatives vere prepared according to the procedures of R. L. Shriner and R. C. Fuson, f*Fhe Systematic Identification of Organic Compounds," 3rd ed., Wiley, New York, N.Y., 19^5*

Ketone 1 hydrogenates in ethanol with 5? palladium on carbon as cata lyst to form bicyclo[Jf.2.2]decan-7-one (]*, 95?), mp 155-157° (Equation

26). The structure of ketone 4 is confirmed by its infrared absorption at

1720 cm"1, nmr a b so rp tio n a t 6 2.3 (d imposed on m, ^H, H at C-l, 6, 8), and 1 .7 (m, 12H, H a t C-2, -3 , -k , -5# -9 t and -10)j and its mass spectral 19

n f n Ha > - 3 10$ p a -0 \ y

CHaNa (2 6)

Ha 596 Pd-C

parent ion (m/e) of 152. Ketone 4 is also characterized as its 2,4- 20 dinitrophenylhydrazone, (mp 1T9- 5-181°), vhich has the proper mass spec trum (m/e t= 332) and combustion analysis. Bicyclo[4• 2.2]decan-7-one semi carbazone ( 5 ) is prepared in ethanol-water as vhite crystals (Equation 5 26) ( 6096, mp 208-210°, lit mp 205-207°). Further purification of £ from

5096 aqueous ethanol produces the pure derivative vith proper combustion analysis and mass spectrum (m/e = 209), mp 220- 222°.

Ketone 4 vas prepared independently from bicyclo[4.2.1]nonan-9-one 2 9 (6). Bicyclo£4.2.13nona-2,4,7-trien-9-one hydrogenates in ethanol over

(29) C. D. Gutsche and T. D, Smith, J. Amer. Chem. Soc., 82, 406? (i 960).

596 palladium on carbon to ketone 6 (8596), mp 98- 101° ( l i t mp 109- 111°) 20

(Equation 26). Ketone 6_ is characterized by its infrared absorption at 29 ~ I 7U0 cm"1 ( l i t 1737 cm"1), mass spectrum (m/e « 138), and nmr absorptions at 5 2.3 and 1.55 (m superimposed on m). Reaction of <5 with excess diazomethane in ether-methanol at 0° for 5 days yields ketone U (K#, Equa tion 26). Saturated ketone ^prepared in this manner is identical gas chromatographically and spectrally vith the product prepared by hydrogena tio n o f 1 (Equation 26).

The structure of epoxide 2 1b assigned from its combustion analysis, spectral properties including infrared absorptions at 960, 860, and 7^5 cm"1, and nmr absorptions at 6 6 .1 (m, 6H, H at C-2, -3, -^, and - 3 ), 3*3 (d ,

2H, H at C-9 and -10), 3.0 (s, 2H, H at C-21)# and 2.75 (m, 2H, H at C-l and - 6), mass spectrum [m/e <= 1^6), and its chemical origin. According to ao previous vork, nucleophilic addition to bicyclo[l*. 2. 1]nona- 2,U,7- t r i e n - 9-

(30) T. A. Antkowiak, D. C. Sanders, G. B. Trimitsis, J. B. Press, and H. Shechter, ibid. t 9j£, 5366 (1972).

one is sterically directed by the lack of steric hindrance on the side of 31 the carbonyl group facing the tvo-carbon bridge. Thus, reaction vith

(31) Molecular models reveal that bicyclo[4.2.1]nona-2,U,7-trien-9-one is a h ig h ly s tra in e d r ig id compound in vhich th e C-7 and -8 o le fin ic bond is almost coplanar vith C-l, - 6, and -9 1 the plane of C-l, C- 6. and C-9 is — 60° out of the plane of the strained planar C-2, -3# -&# and -5 diene moiety in vhich its C-C bond angles are ~ 133°.

phenyllithium, methyl magnesium bromide, and sodium borohydride a ll occur by nucleophilic approach from the C-7 and -8 monoene sid e o f th e m olecule 21 to form the 9-phenyl, 9-methyl, and parent syn- 9 -hydroxyblcyclo[^. 2. 1]- 3 2 nona- 2 ,lf,7-trlenes, respectively. By analogy, ketone 1 and epoxide 2

(32) Bicyclo[U.2.1]nona-2,U,7“trienea vith the 9-subBtituent on the side of the diene bridge are denoted as syn.

are formed by nucleophilic approach of diazomethane from the lesser hindered anti-side of the bicyclo[4.2.1]trienone forming the zvitterionic interme d ia te 7t vhich collapses to products (Equation 27).

©/" > © 'v .CH2N2

(27)

Ketone 1 vas isolated preparatively from the crude diazomethane ring expansion reaction mixture by (l) formation and separation of the semlcarbazone and regeneration of ketone 1 in pyruvic acid under argon at 25 °

(Equation 28) or more advantageously by ( 2) reaction of the crude ring expansion product vith Girard's Reagent *P in refluxlng acetic acid-ethanol- vater and hydrolysis of the vater soluble adduct vith concentrated hydro 22 chloric acid (Equation 28). The pure ketone isolated via the semicarba- ssone method (20-25^ overall) or the Girard's T method (^5-30^ overall), distills at 71- 73° (0 .1 mm) and may be stored successfully in the dark at

- 25 ° for several months.

0 0 0 II \\H NH2NHCNHa CH3 CCOH + I

G ira rd 's Reagent T

Ketone 1 forms enolate anion 8_ readily. When an nmr sample of 1 in carbon tetrachloride is treated vith several drops of deuterium oxide containing a trace of sodium deuteroxide for 12 h r , a n ti - 8-deuteriobicyclo-

[l+.2.2]deca-2,lf,9-trien-7-one (9) is formed. The structure of j? is assigned on mass spectral data (m/e = lVf), infrared carbonyl absorption at 1700 cm-x, and nmr absorptions identical in shift and pattern to 1 except that the multlplet at 6 2.55 becomes much more complex and integrates to a single proton. The assignment of the stereochemistry of deuteration at C -8 is based upon deuteration from the less hindered anti-side of the enolate 8 23 (Equation 29). Such steric control allows rapid monodeuteration compared

OD (29) -HOD

8 to relatively slow dldeuteration; since the anti-deuterium on is steri-

cally less hindered to base, deuterium removal to reform enolate 8, occurs more readily than does deprotonation to form deuterio enolate 10 (Equation

30 ).

OD OD (30) HOD

Longer exposure in base-catalyzed deuteration results in loss of steric control and formation of 10. Further, reaction of the nmr sample vith deu terium oxide and more sodium deuteroxide for 12 days vas required to ex change completely both methylene protons at C- 8. The product, 8, 8-dideuteriobicydo[k.2.23deca-2,Jf,9-trien-T-one (ll), vas identified by its mass spectrum (n/e = llfB), infrared carbonyl absorption at 1700 cm-1, and nmr absorptions similar in chemical shift and pattern to 1 except the multlplet * a t 6 2.33 vas completely absent (Equation 3l)« Ketone 11 Is formed much more advantageously under more forcing con ditions. Reaction of 1 vith a three-fold excess of potassium t-butoxlde in hexamethylphosphoramide at 0- 5° f o r 1+ min, quenching vith deuterium oxide, and finally neutralization with boron trifluoride etherate yields 31 (75$), bp 72-76° (0.1 mm) (Equation 32) vhich is identical spectrally vith dideu- terioketone 11 prepared previously.

Ketone 1 reacts vith excess tosylhydrazide in ethanol as catalyzed by concentrated hydrochloric acid to produce bicyclo[l*. 2 .2]deca-2,lf ,9 - t r ie n - 7- one tosylhydrazone (12) in 71% yield, mp 156 -I 580. The structure of 12 is assigned based upon infrared N-H stretching absorptions at 3^50 and 3250 cm-1, nmr absorptions at 6 7.52 (m, 1H, -K-H), 7.52 (AB, 1*H, aromatic C-H),

5.9 (m, 6H, H a t C-2, -3 , -h, -5 / -9, and -10), 3 .5 (quintet, 3H, H at C- 6),.

2 .9 (m, 1H, H a t C -l), 2 .5 (m, 2H, H a t C- 8) , and 2.1*5 (s , 3H, m ethyl C-H) as veil as itB combustion analysis and mass spectrum (m/e = 31^). Blcyclo- £lf.2.2]deca-2,4,9-trien-7-one benzenesulfonylhydr^one (l^) is formed simi

larly from 1 and benzenesulfonylhydrazide in ethanol, mp 62- 65 ° (85 )»

Infrared absorption at 3500 and 3^5° cm"1, nmr absorptions at 6 7.90 (m, 2H,

H at ortho aromatic C-H), 7.55 (n> 3H, H at met a and para aromatic C-H),

5.70 (m, 6H, H at C-2, -3, -1*, -5, -9, and -10), 3.5 (q u in te t, 1H, H a t

C-6), 2 .9 (m, 1H, H a t C -l), and 2.5 (®> 2H, H a t C- 8), and conibustlon

analysis support the structure assigned to 13. 33 Tosylhydrazone 12 reactsv ith excesB methyllithlum (k equiv) in

(33) R. Shapiro and M. Heath, J. Amer. Chem. Soc., 8^ 573^ (19&7).

hexane a t 25 ° to form bicyclo[4.2.2]deca-2,U,7,9-tetraene (lk, 78?G), c ls -

9 , 10-dihydronaphthalene (< 1?), and naphthalene (W (Equation 33). Tvo very minor products vere not identified. Tetraene 1^ is characterized by nmr

absorptions at 6 6.12 (m, 2H, H a t C-2, - 5 ) , 5*7^ (m, 2H, H a t C-3,

5.50 (m, i*H, H at C-7, - 8, -9 , and -1 0 ), and 3.15 (w, 2H, H a t C -l, - 6).

Double Irradiation of the absorption at 6 3*15 simplifies the absorptions at

6.12 and 5 .50 (to singlet) (see Table II). Tetraene lj+ also has the same 34 retention time as an authentic sample. cis-9.10-Dlhydronaphthalene vas 26

{3*0 Authentic samples obtained from Dr. M. J. Broadhurst.

3 4 identified by glc retention time comparison to authentic samples ; naph thalene vas characterized by identical infrared and nmr spectra, and mixed melting point vith a known sample. This preparation of bicyclo[U.2.2]- deca-2,J*, 7, 9-tetraene (lU) represents a more advantageous and rapid route 3 - 1 0 than methods previously reported.

Ketone 1 provides an extremely useful synthetic entry for preparation of 7-substltuted bicyclop.2.2]deca-2, k,'!,9-tetraenes. The easily enoli- zable 1 reacts vith isopropenyl acetate using £-tolueneaulfonic add as catalyst to form 7-acetoxybicyelo[l*. 2 .2]deca-2,l*, 7, 9-tetraene (1J5), bp 78-79°

(0,005 mm) in 8 6 ?G yield (Equation 3k). Supportive data for the assigned

0 II

structure of 15 include infrared carbonyl absorption at 1760 cm"1, nmr absorption at 6 6.10 (m, 2H, H a t C-2, -5)> 5*69 (m, 2H, H a t C-3, -U ), 5*^9

(ra, 2H, H at C-9, -10), 5*35 (dd, 1H, H at C- 8), 3*23 (m, 2H, H at C-l, - 6), and 2.03 ( 8, 3H, methyl C-H) (see Table II), and combustion analysis.

Proton assignments were made by nmr double Irradiation experiments; irra diation of the bridgehead multlplet at 6 3*23 caused the absorbances at 6

6. 10, 5 , 1*9 (to s), and 5.35 (to s) to simplify significantly. 27

Ac id-catalyzed condensation of 1 with pyrrolidine gives 7-pyrrolidinobicyclo[4.2.2]deca-2,4,7,9-tetraene (l 6^ Equation 35)# an extremely hygro scopic enamine. The structure of the tetraene 16 is assigned on the basis of its exact mass (m/e = 199) and its nmr absorptions at 6 6.15 (m,

2H, H a t C-2, - 5 ), 5-80 (m, 2H, H at C-3, -4), 5.55 (n, 2H, H at C-9, -10),

4.15 (dd, 1H, H at C-8 ), 3*40 (m, 2H, H at C-l, - 6) as well as those at

3.00 and 1.83 (two multiplets, 8h, H on pyrrolidino residue) (see Table Xl).

(35)

Enolization of 1 in basic media also allows synthesis of 7-substituted bicyclo[4.2.2]deca-2,4,7,9**tetraenes. When 1^ is treated vith 3 equivalents of potassium t-butoxide in glyme for 4 min at 25 ° and quenched with methyl fluorosulfonate, a product mixture results in vhich 7-methoxybicyclo£4.2.2]- deca-2,4,7,9-tetraene (17) is the major constituent Equation 3 6 ). S ig nificant amounts of C-alkylation also occur; 8-methylbicyclo[4.2.23deca-

2,4,9-trien-7-one (lg, 26^) is formed. An unidentified component is also formed ( 20^) and there is recovery of IL *( 10I?G). All compound were separa ted by preparative glc.

The structure of methoxytetraene 1£ is assigned on the basis of infrared absorption at 1670 cm"1, nmr absorptions at 5 6.10 (m, 2H, H at C-2, - 3), ♦ • 3.65 (m, 2H, H at C-3, -*•■)*, 5.48 (m, 2H, H at C-9, -10), 4.50 (dd, 1H, H 2 8

CH3 v CH3

X1 3 e q u lv 2. CH3OSQ2F

23L 18 22. a t C-8 ), 3.40 (s, 3H, methyl C-H), and 3.20 (m, 2H, H at C-l, - 6) (se e

Table II), proper combustion analysis and the parent mass spectral ion

(m/e » 160). Furthermore, double irradiation experiments verify the proton nmr assignmentst decoupling of bridgehead protons (C-l, - 6 ) absorption at

6 3 .2 0 simplifies the absorptions at 6 6. 10, 5.48 (to s), and 4.50 (to s), thereby supporting assignment of these protons as adjacent to the bridge head’. Purified methoxytetraene 17_ is homogeneous upon glc analysis) no signs of decomposition or rearrangement are observed.

Dimethylketone lg is difficult to purify and begins to deconpose vhen stored over a day at -25°. The exact mass spectral measurement of 19 sup ports its structural assignment (m/e = 174). Ketone 19 shows infrared car bonyl absorptions at 1700 cm' 1 and gem-dimethyl absorptions at 138O and

I 37O cm-1. Nmr absorptions at 6 5 .9 6h, H at C-2, -3, -4, -5, -9, and

-10), 3.5 (m, 1H, H at C-6), 2.6 (m, 1H, H at C-l), and 1.2 (d, 6H, m ethyl

C-H) also confirm the structure of lg. Methylketone 18 Is presumed to be a reaction product because mass spectral analysis of recovered ketone 1, displays a small mass peak (m/e = 160) consistent vith the presence of lB. 29 Treatment of ketone 1 vith less base results in less efficient methylation; reaction of !L with 1.25 equivalents of potassium t-butoxide and sub sequent quenching with methyl fluorosulfonate in glyme results in recovery of 1 (23%), and formation (Equation 37) of methoxytetraene 1£ (27%)# and methylketone 1 B (6%), No dimethylketone is observed.

1. t-BuO K 1.25 equiv +

Polar solvents enhance the efficiency of O-alkylation. When 1^is treated vith 3 equivalents of potassium t-butoxide in hexamethylphosphoramide a t 0- 5 ° fo r k min followed by methyl fluorosulfonate, methoxytetraene

17 is the major product (92#). Other products include dimethylketone Iff

( 3*°#)/ 2-methoxy-3,4-dihydronaphthalene ( 20, 0 .6# ) , and 2-methoxynaphthalene

(1.5#) along with recovered ketone 1 (2.5#) (Tables I, VII) (Equation 38).

Similar resultB are obtained when the reaction is run in dimethylformamide at 0-5° (Table I). Methyl ether 20, dimethylketone 19, and 2-methoxynaphthalene are assigned on the baBis of glc retention times compared to authen tic samples as well as by nmr analysis of the unpurlfied mixture. Methyl e th e r 20 vas prepared Independently by methylation of enolate anion of 0- tetralone in dimethylformamide.

After a portion of the above results were published in preliminary 3 5 form, reaction of 1 with' potassium t-butoxide and dimethyl sulfate in 30

1. t-Bu0®K®, 3 equiv 2. CH3OSOaF

IT ML (38) UUOCH3 OCH3 20

(35) J. B. Press and H. Shechter, Tet. Letters, 2677 (1972).

dimethylsulfoxide at 0-10 vas reported to form methoxytetraene 17 con- 3 6 taining methyl ether 20 as a significant contaminant. Further, it vas

(36) (a) M. J. Goldstein and S. A. Kline, ibid., IO 85 (1973)» (b) S. A. Kline, Ph.D. Thesis, Cornell University, 1972.

reported that if enolate 8 is allowed to stand for 20 min before methyla- 3 6 tion, only ether 20 is produced. The reported product mixtures vere 36b analyzed using infrared spectroscopy. This report by the Cornell group conflicts greatly with results observed by this Investigator.

Enolate anion 8, though generated essentially quantitatively (Equation

38), does rearrange slowly. When the methylations are run after longer contact times with the base, there is a decrease in the yield of methoxy tetraene 1£ and a concomitant increase in the byproducts obtained (see

Table I). After a contact time of 2U.5 hr at 0° with the base and then methylation, the major product is s till tetraene IT (60?G) but significant amounts of methyl ether 20 (1C#>) and 2-methoxynaphthalene (12#) are formed.

During the study of the methylat ion of enolate f3, methyl ether 20 never was observed as the major reaction product. In addition, enolate 8 formed uBlng a two-fold excess of potassium t-butoxide in dimethylformamide at 0° for 0,5 hr reforms ketone 1, ( 92#) upon quenching with water* no (3-tetralone is observed under conditions where > 2# could be detected. In the present investigation, the rapid rearrangement of enolate 8, to the enolate anion of p-tetralone as reported by the Cornell group is not observed.

These observations conflicting with those reported by Goldstein and 36 Kline are in part explainable by the differences In work-up procedures and product analysis. Work-up of the methylat ion reaction of enolate (3 in dimethylformamide by the Cornell workers involves removal of the majority of solvent under reduced pressure. In this laboratory, attempts to Isolate methoxytetraene IT in a similar manner result in material loss due to vola tilization of IT. Furthermore, infrared analysis of the product mixture by Goldstein and Kline im plicitly assumes the presence of only two compo nents j in this author's experience at least five components are present in the product mixture obtained (Table I, Equation 5 8 ). Upon exam ination of the large number of reproducible, consistent and high yield experiments reported herein, the accuracy of the Cornell report must be seriously ques tio n e d . T able I

Product Distribution from Reaction of Bicydo[U.2.21deca-2,^,9-trien-7-one (l) with Potassium

t-Butoxide and Methyl Fluorosulfonate In Polar Solvents

Potassium t-Butoxide, ^— — Product Percentage — N contact time,0, 0-10° Solvent 17 1 20 0O'0CH3

^ m in3 hexametbylphosphoramide 92.2 2 .5 3 .0 0 .6 1.5

k min dimethylformamide 95.0 5 .1 2 .8 0 .2 0 .9

1^ min hexamethylphosphoramide 91.0 0 .8 5.5 1 .2 1 .0

30 min dimethylformamide • 82.0 7 .1 1 .0 5.5 2 .6

12 h r dimethylformamide 72.0 1 .0 1.0 T.4 16.0

2^.5 h r dimethylfarmamide 60.0 3 .5 1 .5 10.0 12.0

aTypical reaction used 3 equivalents of potassium t-butoxide. ^Average of seven reactions, see Table VII. 33 Naphthalenic products formed during the enollzatlon of 1 and subsequent quenching probably arise through an Internal Diels Alder ring closure followed by ring opening (Equation 39). Subsequent bond reorganization

(path a) and quenching produces 20; quenching of the c 1b -9, 10-dihydro-2- naphthoxide followed by oxidation (path b) leads to 2-methoxynaphthalene.

Enolate £ also acylates and silylates readily. Ketone 1 treated with two equivalents of potassium t-butoxlde in glyme for 5 min followed by reaction with acetyl chloride produces acetoxytetraene 15 ( 83#) and an un identified material (9^) along with recovered !L (816) (Equation ho). When

reacts with four equivalents of potassium t-butoxide in glyme for 5 min and then tr 1 methylsilyl chloride, 7-trimethylsiloxybicyclo£lf.2.2]deca-

2,^,7*9-tetraene (21, 72?S) is producedj some 1^ (1$) is recovered (Equation

40). II OCCHs OSiCCHaJa 0 II CH3 CCI (CH3)3S1C1 (ho)

The structure of silyl ether 21 Is assigned on the basis of Infrared absorptions at 1660 and 9^0 cm"1; exact mass measurement (m/o = 218), and nmr absorptions at 6 6.15 (m, 2H, H at C-2 and - 5 ), 9*75 (n, 2H, H at C-3,

-M , 5.50 (m, 2H, H a t C-9, -1 0 ), ^.78 (dd, 1H, H a t C-8), 3 .lB (m, 2H, H at C-l, -6), and 0.11 (s, 9H, methyl C-H) (see Table II). Silyl ether 21 decomposes upon standing several hours in the atmosphere.

It is possible that the 7-substituted tetraenes ljj, 16, 17/ and 21, as prepared initially, isomerize rapidly to 3-substituted bicyclo[4.2.2]- deca-2,4,7,9-tetraenes (22-2^) via internal addition (internal Diels Alder reaction) and opening (retro Diels Alder) analogous to similar tetra- X2 18 X7 enes ’ ' (Equation 4l) and thus the structural assignments might be in

0 11 15 , r=occh3 22 3 . 17, R=0CH3

21, R=0Sl(CH3 )3 3 * 35

error. All of the substituted tetraenes presently prepared revert quanti

tatively to ketone 1 upon hydrolysis (Equation 42) and hence the tetraenes

H30 (te)

i 1-32/ 21

are substituted exclusively at the C-7 position. Compounds lg, 17^ and 21 were purified by preparative glc at temperatures up to 200°; it is likely that these 7-subBtituted tetraenes are more stable than are their 3-substi tuted isomers.

Comparison of the nmr of ljj, 16, 177 and 21 (Table XI) as well as that for previously reported tetraenes (Table III) indicates that there are strong inductive effects of the 7-substituent on the proton at C-8. Com pared to the unsubstituted tetraene 14 with C-8 proton absorption at 8 5*5* electron-withdrawing grot$>s at C-7 cause significant shifts downfield whereas electron donors produce large Bhifts upfield. Thus the 7-bromo- 10 and 7-acetyl derivatives show absorption for their C-8 protons at 8 5A and 6.7, respectively, whereas the 7-acetoxy- ( 15 ), 7-methyl-, 7-trimethyl- siloxy- (21), 7-methoxy- (17), and 7-pyrrolidino- (l6) derivatives display absorptions at 8 5*35# 5*28, 4.78, 4.50, and 4,15, respectively.

Methoxytetraene displays expected thermal behavior at elevated temperatures. When 17 is heated for 0 .5 hr at 200° in dry hexamethylphosphoramlde, unrearranged tetraene is recovered (73?>) along vith naphthalene

(17.0^) and 2-methoxynaphthalene (10^). Heating 17 neat in a sealed 3 6

T able n

Nmr Data Observed for 7-Substituted Bicyclo[if.2.2]deca-2,U,7#9“

Tetraenes lU, 15, 16, 1J, and 21

- NMR, s h i f t in 6 - — ------N r R H a,s H3,4 H s ,io Ha Hx,a R

a i -H, lJt 6 .1 2 5.7^ 5.50 5.50 3.15 5.50

-OAc,a 1§. 6 .1 0 5-69 5.^9 5-55 3.23 2.03

-0Si(CH3)3, 21 6.15 5.T5 5.50 U.78 3.18 0 .1 1

-OCH3, a 17 6 .1 0 5.65 5 .^8 h.50 3.20 3.40

6.15 5.80 5.55 U.15 3 .^ 0 3 . 00, -O- 1.85 aProton assignments based on double irradiation experiments. 37

T ab le I I I

Nmr Data Reported for Substituted Bicyclo[4.2.2]deca-2,4,7*9-tetraenes

NMR, shift In 6

Substituent Hb,5 H3#4 H7 Hs Ha, 10 H i,e

2 4 7-CHa 6 .4 -5 .7 6.4 -5 .7 5.28 5.5 3.07 xo 7-Br 5.9 5.9 5.4 5.9 3.4* 3 -1 10 7-CO2CH3 5.8 5.8 6.7 5.8 3 .8 , 3 .3 12 7,8-(cO aCH3)2 6.18 5.86 5.67 3.70

0 0 3*4- A‘0 0 A - 7.55 5.78 5.78 5.78 3.55-3.8

0 0 14 3 A - A jjh A 6.50 4.75 4.75 4.75 2.3-2.7

0 0 3*4- T'22 5.79 5.79 5.79 3.5-3.7

14 3, 4 - / - ° - \ 6.10 5.69 5.69 5.69 3.1-3.3 38 evacuated tube for 21 hr results in formation of methanol, naphthalene (60$) and 2-methoxynaphthalene (3 0 $), and recovery of methoxytetraene 1£ (10%)

(Equation 1+3) - Thermolysis of 1£ probably occurs via an allowed internal

200 OCH3 + CH3OH + H2

(1+3)

Diels-Alder reaction and disallowed opening to the c!b-9j 10-dihydronaphthal ene derivative which then aromatizes (Equation hU). Path a is favored over path b by about 2 : 1 . 2-Msthoxynaphthalene was identified by comparison

-CH3OH

OCH3

OCII3

V o c H a

3 3 * V 39 of its nmr, ir, and mixed melting point vith an authentic sample prepared from 2-naphthol, sodium hydride and methyl iodide in dlmethylformamide (89^).

Ketone 1 may also he functionallzed in the C-6 position via its enol.

When 1 is refluxed in acetic acid containing one equivalent of lead tetra acetate, antl-8-acetoxyblcyclo[4.2.2]deca-2, b,9-trlen-T-one (26) is quan titatively formed as pale yellow crystals, hp 9lt-96° (0.0U mm), rap 81-82°

(Equation 1+5)* Combustion analysis, mass spectroscopy ( m/e = 20b), in fra re d 0

2 6 absorption at 17^0 for carbonyl stretching and 1220 cm"1 for oxygen- carbon stretching, and nmr absorptions at 6 9*9 (m, 6h, H at C-2, -3, -k,

-5, -9, and -10), 5.35 (m, 1H, H a t C -8), 3 .6 (m, 2H, H a t C -l, -6 ) , and

2.0 (s, 3H, methyl C-H) confirm the structure of 26. The stereochemistry is assigned on the basis of a probable reaction mechanism (Equation U6) invol ving (l) carbonyl oxygen coordination vith lead tetraacetate and concommltant

/ 0Ac

ffiD Pb(QAc ) 3 0Pb(QAc)g

-Pb(0Ac), QAc0 4 0 expulsion of acetate and hydrogen ions to produce enol lead IV complex gj

and ( 2 ) attack of ZJ_ "by acetate ion from the lesser hindered side (anti

to the diene bridge) to produce 26 (Equation 46). Intermediate 27 may also

collapse to 26 via a cyclic process occurring favorably from the anti

d ire c tio n .

Attempts to prepare 8-hydroxybicyclo[4.2.2]deca-2,4,9-trien-7-one from

aoetoxyketone 26 via acid-catalyzed transesterification failed. Refluxing

26 in methanol vith £-toluenesulfonic acid as catalyst quantitatively pro

duces syn- and anti-8-methoj{ybicyclo[4.2.2]deca-2,4>9-trien-7-ones ( 28 and

2j>) as a 93:7 mixture (Equation 47). The structures of 28_ and 2^ are assigned

' from infrared absorptions at 1720 cm-1, nmr absorptions at 6 5.8 (m> 6h, H

at C-2, -3, -4, -5, “9, and -1 0 ), 4 .0 5 (dd, 1H, H a t C -8), 3 .7 (m, 2H, H a t

C-l, -6), and 3.35 (s> 3H, methyl C-H), mass spectra (m/e = 176) and com

bustion analysis. The major isomer is believed to be the syn-methoxy-

ketone 28 on the basis of mechanistic principles (Equation 48); a likely

p a th to 28 involves formation of methylhemlketal 30, elimination of water

to give 7-acetoxy-8-methoxybicyclo[4. 2 , 2]d eca-2, 4 ,7 ,9-tetraene ( 31), t r a n s

esterification forming the 7-hydroxy- 8-methoxytetraene £ 2 , and tautomeri-

zation of enol 32 via attack of a proton from the lesser hindered anti- Ul

0 II OCCH3

HaO

5° £L

m u _ HO. a H CH30 - p Y O

side. Ketone 28 is the major product. Reaction from the syn-side produces the minor product. Methoxyketone 28^ is further characterized as its 2,U-

dinitrophenylhydrazone of proper combustion and mass spectral analysis

(m/e « 356 ).

Acid-catalyzed hydrolysis of acetoxyketone 26 failed. When 26 is heated in dimethylformamide-vater for 8 hr vith j>-toluenesulfonic acid, 2£

is recovered ( 83%). The unidentified minor products shoved aromatic

nuclear magnetic resonances.

Base-catalyzed enolizatlon of 1 provides for further functionaliza- tlon at C-8. Reaction of 1 vith 10 equivalents of potassium t-butoxide and

excess isoauyl nitrite in t-butanol 3 gives 7 bicyclo [ 4 .2.2]deca-2,4,9-trien- 4 2

7, 8-dione monoxime (3J>, 6yf>) (Equation 1+9)* The yellow solid, mp 178-178.5°, is pur if iable in methylene chloride-hexane and is characterized hy conibuB- tion and mss spectral (m/e = 175) analyses, infrared absorptions at 3300#

N-OH

t-BuO ®K® (49) t-BuOH isoamyl nitrite a

(57 ) A modification of the method of P. Litvan and R. Robinson, J. Chem. Soc., 1997 (1938).

1710, and 1690 cm”1, and nmr ab so rp tio n s fi 5*9 (m, 6h, H a t C-2, -3# -4 ,

-5, -9, and -10), 4.3 (dd, 1H, H at C-l), and 3.7 (m, 1H, H at C- 6).

Oximinoketone is converted by o-phenylenediamine in acetic acid to the quinoxaline of bicyclo[4.2.2]deca-2,4,9-trien-7>8-dione (j54)> np 194*5-

195° (Equation 50). The quinoxaline is identified by its infrared and masB

spectral properties (n/e = 232), proper combustion analysis, and nmr

NOH

NHa \\ (50) aNHa S t absorptions at 6 8.02 and 7.67 (two multiplets, H on aromatic nucleus),

6.1*7 (m, 2H, H a t C-2, -5 ), 6.02 (m, 2H, H a t C-9, -1 0 ), 5-82 (m, 2H, H

at C-3, -4), and 1*.35 (n# 2H, H at C-l, - 6). Proton assignments fcr Jjf

are based on double irradiation) irradiation of the multlplet at 6 1*.35

(H at C-l, - 6) causes simplification of the multlplet at 6.1*7 and collapse

of the absorption at 6.02 to a singlet.

Comparison of the nmr absorptions of quinoxaline %hj bicyclo[4.2,2]-

deca-2,lf,7>9“‘tetraene (l&), and 7,8-dicarbomethoj^bicyclo[l*.2.2]deca-2,lf,7>9- la te tra e n e ( 39) shows the large inductive effect of the quinoxaline moiety.

.82

6 5*86 -s? 6.02 6 6. 12^ 6 3.15

'As expected from their similarities in symmetry, lj*, and display

identical line shape patterns in the nmr of the vinylic region. Diester

35 , a relatively electron deficient tetraene, shows sizeable downfieM

nmr shifts for protons at C-l, - 6, -2, -5, -9, and -10 (Table II) relative

to the parent lA (O. 65 , 0.29, and 0.35 6, respectively). Quinoxaline 3j*

reveals even greater downfield shifts for such protons ( 1.20, O.35 , and

0.52 6 units, respectively). These shifts probably stem from inductive

effects since they fall off with distance from the substituent; neither

3|f nor show any noticeable nmr shifts for their protons at C-3 and -If. Uh

Attempts to convert oxlminoketone ^ to bicydo[4.2.2]deca-2,4,9- 3 8 t r i e n - 7* 8-d io n e ( 36) failed; reagents such as thallium trinitrate, lead 3 9 4 0 tetraacetate, sodium bisulfite, and levullnlc acid did not cause con-

( 38) A. M cKillup, J . D. H unt, R. D. N aylor, and E.- C. T ay lo r, J . Amer. Chem. S o c ., §3/ **918 (1971).

(39) S. H. Pines, J. M. Chemerda, and M. A. Kozlowski, J. Org. Chem., 31. 5^6 (1966).

(l+O) C. H. DePuy and B. W. P onder, J . Amer. Chem. S o c ., 81, U629 (1959).

version of 22. to diketone (Equation 51). Attempted conversion of oximino- keto n e 22. ^ 7-diazobicyclo[U. 2 . 2 ]d e c a -2, k , 9 - t r i e n - 8-one (^T^) using alkaline chloramine also failed (Equation 51*)•

NOH

■*— W- (5 1 )

5 £ 51

Ketone 1 may a ls o b e fu n c tio n a liz e d a t C -8 by base-catalyzed condensa tion vith methyl formate. When 1 is exposed to four equivalents of sodium methoxide and excess methyl formate in ether, 8-formylbicyclo[l+. 2 . 2 ]- deca-2,h,9-trien-7-one ( 3 8) forms, mp 58-57°* 95^ yield (Equation 52).

Maes spectral data (m/e = 17*0* proper combustion analysis, infrared car bonyl absorptions at 1660 and 1580 cm**1, and nmr absorptions at 6 8 .1 (a ,

1H, aldehydic C-H), 5.9 (®* 7H, H at C-2, -3, -h , - 5 , - 8, -9, and -10), and 3 .5 (m, 2H, H a t C -l, - 6 ) support the structural assignment of 28. h 5 CH

(52)

Fornylketone ^Q_ is converted to 2,4-diazatricyclo[5.4.2.02' Q3trideca- ^, , . 4 1 2, 5 . o, 10, 12-pentaene ( 39) by anhydrous hydrazine in refluxlng ethanol

(Equation 53)• Pyrazole 39. formed in 86/6 yield, is a yellow solid, mp

1 3 (53)

10 11

22.

(Ul) Method of W. E. Parham and J. P. Dooley, J. Amer. Chem. Soc., 89* 985 (1967).

106-107°, with infrared absorption at 3250 cm-1, nmr absorptions at 6 9#25

(broad s, 1H, >N-H, shift is concentration dependent, disappears upon pgO addition), 7.15 (&> 1H, H on C-5), 6.2 and 5.7 (multiplets, 6h, H at C-8,

-9, -10, -11, -12, and -13), and if.O (m, 2H, H at C-l and - 7), a proper mass spectral parent ion and a satisfactory combustion analysis. Positions of the double bonds in the pyrazole ring of ^2. ore probably delocalized as shown. Reaction of formylketone 38 vith tosyl azide and triethylamine in 4 a ’ methylene chloride at 25° gives 7-diazobicyclo[l+. 2.2]deca-2, k ,9 -trie n -8 -

(1*2) In a modified procedure of that described by M. Regitz and J . Ruter, Chem. B e r., 101, 1263 (1968).

one ( 37) (Equation 5*0, a yellow solid in 55$ yield. Diazoketone 3£ ex”

OrHrSOgNa

hibits intense infrared absorptions at 2150 for diazo group and 1650 cm-1

for carbonyl group stretching, mass spectral ion at Ikk (P-Ng), and nmr

absorptions at 8 5*9 (®j 6h, H at C-2, -3, -5* -9, and -10) and 3»6?

(m, 2H, H a t C -l, -6 ). Photolysis of diazoketone 37 results in Wolff ring contraction. Thus

irradiation of 37 in dioxane-vater gives b ic y c lo . 2. l]nona-2,^,7-trien-

syn-9-carboxylic acid (U0, 6l% yield) (Equation 55)* Syn-carboxylic acid 1*7

(1*3) D. C. Sanders, Ph.D. Dissertation, The Ohio State University, 1972.

1*0 is identical (ir, melting point, and nmr) vith that prepared hy chromic acid oxidation of bicyclo[l*. 2 . 1 ]nona- 2,l*, 7-trien-s£n- 9-carboxaldehyde.

To determine the homogeneity of the crude photoproduct, carboxyllc acid 1*0 was treated vith excess dlazomethane in ether. The resulting pro duct, methylbicyclo [ 1+. 2 . 1 ] nona- 2, 1+, 7-trlen-syn- 9-carboxylate ( 1*1 , 93%)

(Equation 5 6) is a vhite solid, mp 27-29°# bp 66.5° (0.05 mm) and is homo geneous by glc analysis. The structure of 1*1 is confirmed further by its infrared carbonyl absorption at 1720 cm-1, mass spectral parent ion (m/e =

17^)# proper combustion analysis, and nmr absorptions at 6 5«9 (a, 1*H, H at

C-2, -5, -1*, and -5)# 5.15 U , 2H, H at C-7, -8), 5.5 (b, methyl C-H), superimposed on 3.3 (®» H at C-l, - 6, -9, total 6h ).

CH3OC

(56)

1*1

The mechanistic aspects of the Wolff ring contraction and hydration * process allow the prediction that 1*0 is the oyn-carboxyllc acid (Equation

57 ). ThuB the carbenic Intermediate 1*2 from gT. (Equation 57) isomeriees t o k eten e k%_ which hydrates by processes in which a proton is delivered to

C-9 from the anti-direction. . Protic decomposition of dlazoketone also results In profound structural rearrangements. Thus £7 reacts with glacial acetic acid at 25° to yield ia mixture of exo- and endo-2-acetoxyb lcyclof 5.2. lldeca-3 , 5, 8-trien-

10-ones (44 and 4;?) (E quation 58 ), respectively. D istillation removes the

II ch3coh

! £ minor endo-acetate 4j^ from jj4. The structural assignment of 44 is supported by infrared absorptions at 1760 and 1740 cm-1 for ester and ketone carbonyl stretching, ultraviolet absorption maxima in ethanol at Xmax 200, 225, and 285 nm (cmrtv. = 6080, 4000, and 600, respectively), mass spectral parent ion (m /e) of 204, and proper combustion, analysis. Nmr absorptions at ( 5*9

(m, 6H, H at C-3, -4, -5, -6, -8, and - 9 ), 5.00 (t, 1H, H at C-2), 3.21

(m, 1H, H a t C -7), 3>°5 (dd, 1H, H a t C -l), and 2 .U (s , 3H, H on methyl

C-H) also support the structural assignment of 44. Double irradiation of * * ♦ the absorption at 6 3.05 simplifies the triplet at 5*00; irradiation of the triplet causes simplification of the absorption at 3* 05 * This decoupling Indicates that the proton bound to carbon substituted by acetoxyl is adjacent to a bridgehead proton.

Exo stereochemistry at C-2 of 44_ is assigned on the basis of mechanistic consideration (Equation 59); initial proton delivery to dlazoketone pro-

51 46

CH3CO-^a« 0 I* //

CH3CO"

bably occurs from the less hindered anti-side of the dlazoketone to form the protonated diazo intermediate 46. Nitrogen probably leaves vith back side stabilization by the monoene (C-9> -10) bridge vith subsequent col lapse to the bishomotropylium ion 47* Combination with the counter-ion is more likely to occur from the less hindered exo-side of cation 47 via path a (Equation 59) to produce the exo-acetoxyketone 4U as the major product.

Attack from the endo-slde of ljT is much less probable due to sterlc Inter ference of the monoene bridge and is a minor process.

An alternative product from decomposition of dlazoketone £7, by acetic acid could result from migration of the diene bridge to the carbonlum ion formed at C-8 (Equation 60). Such migration would give bishomotropyllum

51 (60)

cibco'1 1 .

& ion {(8 in a manner analogous to electrophlllc additions to bicyclopi.2,2]- deca-2,4,7>9-tetraenes. Finally, combination of acetate ion with M3 would result in exo-7-acetoxyblcyclorM3.ndeca-2,M8-trien-10-one (Uj>).

In order to prove that acetoxyketone Ml is formed instead of Ml was hydrogenated in ethanol with palladium on carbon as catalyst to pro duce exo-2-acetoxybicyclo[5.2.1]decan-10-one (^0), mp Mr-M?0* In 73^ yield

(Equation 6l), The structure of acetoxyketone £0 is assigned from its 51 proper coribustion analysis, mass spectrum (m/e 210) and Infrared carbonyl stretching frequency at 1750 cm"1, and nmr displaying no oleflnic proton absorption) jjO was then saponified in sodium hydroxide-methanol to exo-2- hydroxybicyclo[5.2.l3decan-10-one (j?l) (Equation 6l) as characterized by infrared hydroxyl group stretching absorption at 3^50 and carbonyl group stretching at 1730 cm**1, and by exact mass measurement (m/e « 168).

0 OH (61) Pd/C OH H

Hydroxyketone jSl is oxidized quantitatively vith chromium trloxlde in acetone to bicyclo[5«2.1]deean-2,10-dione (£2) (Equation 6l). The identity of diketone is confirmed by its mass spectrum (m/e = l66), its Infrared carbonyl stretching absorptions at 1730 and 1700 cm-1, and by its proper combustion analysis. Diketone £2 1 b dissimilar in nmr, ir, and physical properties to bicycloP). 3 . 13decan- 7, 10-dione (35) prepared via reaction of 44 1-morpholinocycloheptene and acroyl chloride.

(UU) J. R. Hargreaves, P. W, Hickmott, and B. J. Hopkins, J. Chem. Soc. C, 592 (1969). 52 Diazoketone ££ is decomposed rapidly by hydrogen chloride to exo-

2-chlorobicyclo[5.2.1]deca-3,5,8-trien-10-one (£4) in 94^ yield (Equation

62). Although £4 is too labile to be characterized completely, mass spec-

HC1 (&) -Na

z l a tra l (m/e e= 180) and exact mass measurements, infrared carbonyl group stretching absorption at 1740 cm*1 and nmr absorptions at 6 5*9 (m, 7H> H at C-2, -5, -4, -5# -6, -8, and -9) and 5.2 (m, 2H, H at C-l and - 7 ) a l l support the structural assignment of £4. By mechanistic principles used to account for the formation of acetoxyketone 44, chloroketone £4 Is assumed to have exo-stereochemistry at C-2.

For further proof of the ring system of chloroketone, £4 was hydrogenated 45 in absolute ethanol over palladium on carbon to bicyclo[5.2.1]decan-10-one

(££, 6f l ) (Equation 65 ). The ketone is characterized by its infrared ab-

(45) C. D. Gutsche, T. D. Smith, M. F. Sloan, J. J. Quarles van Ufford, and D-. E. Jordan, J. Amer. Chem. Soc.. 80, 4117 (1958).

H " i _ H a _____ Fd/c (6 3 )

I 53 45 Borption at 1730 cm -1 (lit 1731 cm"*), nmr showing no vinylic proton absorption and exact mass (m/e «= 152). The structure of ketone ££ is con clusively established by conversion to bicyclo[ 5 . 2 . l]d e c a n - 10-one 2 ,4 - o dinltrophenylhydrazone ( 56 ) which melts at 175-176 ( l i t 176-177. 5 ° ) , and shows no melting point depression upon admixture vith an authentic 4 6 sample of 2,4-dinitrophenylhydrazone £ 6. Both samples of ^possess lden-

(46) The author vlshes to thank Dr. C. D. Gutsche for supplying the authen tic sample in a personal communication, May 9» 1973*

& tical infrared spectral properties j the sample of p6 prepared from chloro ketone also gives the proper exact mass (m/e » 332).

Chloroketone is also converted by silver acetate in acetic acid to a mixture of acetojyketones M and 4£ (Equation 64) in 53 % conversion.

0 . II

A2OCOCH3 \ \ CHaCQaH 5^ The spectral properties (ir, nmr# and glc) of the product show that the ratio of Uj* and j+J5 via the silver acetate reaction is essentially the same as the ratio of 4k and obtained from decomposition of dlazoketone 37 catalyzed by acetic acid.

Attempts to purify acetoxyketone W and chloroketone Jjjf by prepara tive glc led to Cope rearrangements. Acetoxyketone rearranges to endo-

6-(cis-2t-acetO3gvinyl)-cis-bicyclor3.3.01octa-3j7“dien-2-one (g7) in 93 % yield at a column temperature of 225° (Equation 65 ) and chloroketone g4 converts to endo-6-(cis-21 -chlorovinyl)-cls-bicyclor3.3.0~|octa-3.7~dlen-2- one

m c 6 OCOCH3 ' \ 0JXQCB9

i t SL

(66) - f /

H The structure of acetoxyketone 57 is assigned in part on infrared ab sorptions of an ester carbonyl at 1760 cm- 1 and an at, p-unsaturated carbonyl a t 1695 cm'1, uv absorption in ether at \ mav 210 nm (e = 31, 500 ), a mass

spectral parent ion (n/e of 204) and coribuBtion analysis. The nmr spectrum

of is suitable for complete analysis by double irradiation experiments and is described as follows: 6 7.50 (dd, J = 6,3, 1H, H at C-4), 7.14 (dd,

J = 6, 1, IB, H at C-2'), 6.08 (dd, J = 6, 1.5, 1H, H at C-3), 5.80 and

5.50 (m u ltip le ts , 2H, H a t C-7 and - 8), 4.69 (dd, J « 10, 6, IB, H at C -l'),

4.14 (t, J = 10, IB, H at C-6), 3.80 (m, 1H, H a t C -5), 3.46 (m, IB, H a t

C-l), and 2.10 (s, 3H, H on methyl group). Results of double Irradiation are summarized in Table IV. Comparison of the nmr of to the model * 7 compound, bicydo[ 3 . 3. 0 ]o c t- 3-en e - 2-one (jjj?), vhich shows nmr absorptions

(47) S. Moon and C. R. Ganz, J. Org. Chem., 5 %, 124l (1970).

6 3.23

& 5.95 (J « 6,2)

& a t 6 7.3 (dd, J = 6,3, 2B, H at C-4), "5.95 (dd, J « 6,2, IB, H at C-3), and 3*S3 (®, 1H, H at C-l) supports the assignment that £7 contains the bicyelo[3.3«0]systera. Assignment of the cis-stereochemlstry of the C-l*-

C-2' olefin is supported by the nmr coupling constant (J s 6 Hz) far the proton absorptions at & 7.14 and 4 . 69. This value is well within accepted 56

Table IV

Double Irradiation of endo-6-(cls-21- Acet oxyvlnyl)-cis- Dicyclo-

[3*3.01octa-3j7-dien-2-one (37)

•Ac r NMR, shift in 6 7.50 7.14 6.08 5.80 5.50 4.69 4 .1 4 3.80 3.46

Irradiation H at C of H at C -4 -2* -3 -7 -8 - 1 * -6 -5 -1

-4 - + - - - -

-2 ' - -- - + +

-3 + - - - --

-7 - - - + - + +

-8 - - - + - + +

-1 ’ - + - - - +

-6 - + - + + +

+ - + -- + + -5 •

-1 __ + + _ +

- no effect

+ pattern simplification upon double irradiation 0 II Shift of CH 3CO- a t 6 2.10 48 valueB for cls-oleflnlc protons (j * 6-12 Hz) whereas i t is far too small for trans-oleflnlc protons (J = 12-18 Hz).

(If8) H. M. Silverstein and G. C. Bassler, "Spectrometric Identification of Organic Conpounds," Second edition, John Wiley and Sons, Inc., New York, N.Y., 1967*

The structure of ££ is further elucidated upon its hydrolysis by aqueous trifluoroacetic acid to endo-6-(l'-oxoethyl)-cis-bicyclo[3.3.0]“ octa-3i7-dlen-2-one (60) (Equation 67) in 75^ yield. The structure of 60 is

at- q S « II V-OCOCH3 CHaCH 60 consistent with its exact mass measurement (m/e = 162), infrared absorptions a t 1715 and 1700 cm"1 for aldehyde and at p-unsaturated ketone stretching, and nmr ab so rp tio n s a t 6 9.80 (s, 1H, H at C -l'), 7.32 (dd, J » 6, 2 .3 /

1H, H a t C-1+), 6.02 (dd, J = 6, 2, 1H, H at C-3)/ 5.6 (m, 2H, H at C-7,

- 8), 3.55 (m, 3H, H a t C -l, -5 , - 6), and 2.6 (br d, 2H, H at C-2'). The coupling constants and shifts of the protons at C-3 and -If are also similar to those of model compound bicyclo[3.3.0]oct-3-ene-2-one (59). The structure of chloroketone £8 is assigned from its infrared carbonyl stretching absorption at 1700 cm-1, ultraviolet absorption in ether at ^

210 nm (e = 31, 300), mass spectrum (m/e = 180), combustion analysis and nmr absorptions at 6 7-50 (dd, J = 9, 2, 1H, H at C-lf), 6.15 (m, 2H, H at C-3, -2'), 5-90 (m, 2R, H at C-7 and -8), If.55 On, 1H, H at C -l'),

3.7lf (m, 2H, H at C-5, -6), and 3-^6 (m, 1H, H at C-l). While complete proton assignment is impossible by double irradiation, partial assignment can be made; decoupling of the absorption at 0 7-5 0 causes simplification of the multiplets at 6.15 and 3-7^, decoupling at 6 3 .b6 simplifies the signals at 5 -90, If.55, and 3*7^, and double irradiation at 6 3-7^ results

In simplification of all other absorptions. (The major coupling of the

Blgnal at 6 7-50 (J = 9) again Indicates that the exocyclic olefin (C-l*,

-2f) of chloroketone is of c is - stereochemistry.

The reactive conformations of acetoxyketone Mf and chloroketone jjjf for Cope rearrangement are consistent vith the structures of the observed products. The two stable configurations of 4jf_ and jjU as derived from molecular models are shown as 6l and 62. Of the conformers, 6l is less

H R b OCOCH3, Cl

61 62 strained and has the greater monoene-diene Interaction. The overall Cope rearrangement from isomeric form 6l for the acetoxyketone and chloro ketone is depicted in Equation 68. The reaction therefore is expected to produce the thermodynamically more stable cls-rlng Juncture and cls- stereochemistry for the exocyclic olefin. 59

- < x > i ( &

H H

44, RsOCOCHa SJj R«0C0CH3

%kj R e d J§8, R=C1

Attempts to reduce ketone 1 via a Wolff-Klshner reaction failed to produce bieyclo[4.2.2]deca-2,4,7-triene (6ft). Rather, ketone 1 reacts with

63 excess hydrazine and potassium hydroxide in ethylene glycol at 170-200° to give 2,3-diazatricyclo[6.3.1.04,11]dodeca-2,5,9-triene (64) in kTf y ie ld along with several minor hydrocarbon products that were not identified

(E quation 69). Fyrazoline 64 is a white solid, mp 170-172°, of mass spectrum

KOH ROCHgL'HgOH 60 (m /e a l 6o) and vith proper combustion analysis. The product displays

Infrared azo absorption at 1650 cm"1; I t s u l t r a v i o l e t spectrum shovs end absorption (\maY 200 nm, = 3, 700) and absorption consistent vith a 4 9 pyrazoline (X^y 333 nm, «meoc *= 330)- The nitrogen-containing product

(lf9) (a) S. 0. Cohen and R. Zand, J. Amer. Chem. Soc.» 8jf, $06 (1962). (b) M. Schvarz, A. Besold, and E. R. Nelson, J. Org. Chem., 30. Zk25 (1965). (c) R. M. Moriarty, lold., 28. 23«5 U963J.

further displays nmr absorptions at 6 6 .0 3 (m, 2H, H at C-9, -10), 3.33 and 5.03 (m, 3H, H at C-lf, -5, and - 6), lf.81f ( t , OH, H a t C -l), 2.80 (m,

3H, H at C-7 and - 8 ) , 2.1f0 (m, 1H, H a t C - l l ) , 2.20 (d , 1H, H a t C -12), and 1.73 (septuplet, 1H, H at C-12).

Information concerning the structure of 61f_ is obtained by nmr double irradiation and europium shift reagent studies. Double irradiation of the absorption at 6 2 .8 0 simplifies only the absorption at 6. 03; decoupling of the trip let at U.&f simplifies the septuplet at 1.73* The europium shift results are summarized in Table V. Assignments of the protons at

C-l and -If and C-U are made baaed on their magnitude of shift; protons closest to the europium complexed azo-linkage should have the largest shift. The olefinic protons on C-9 and -10 and the exo proton on C-12 are the farthest removed from the azo-linkage; these protons shov the least effect in their chemical shifts.

In additional attempts to effect its deoxygenation, 1 vas converted by hydrazine to bicyclo[4.2.2]deca-2, If, 9-trien-T-one hydrazone (65) in 9&f> yield (Equation 70). Hydrazone 6£ shovs infrared absorptions at 3330 and Table V

Eu(Fod)s Induced Chemical Shift Bata far Compound #*

11 F10 5 6k

_ NMR, s h i f t In fi /^ H a t N mole? Eu(Fod)a C-9, -10 A, -5 -6 -1 -7 , -8 -11 -12 -12

0% 6.03 (m) 5.53 5.03 l*.8l* 2.80 2.1*0 2.20 1.73

10? 6.10 — — 5.03 — — 2.55 1.90

20? 6.22 6.1*0 5.70 5.70 3.3 — 2.10

30? 6.1*0 6.95 5.90 6.20 — 3-5 — 2.23

. UO? 6.60 7*60 6.10 6.90 — 3 .8 — 2.60

50? 6.70 8.10 6.35 7. ^ .3 i*.6 3-7 2.80

At Aft/lO mole? O.ll* 0.51 0.20 0.51 0.30 o.to 0.30 0.21 62 3200 cm-1, nmr absorptions at 6 5*8 (m, 6h, H at C-2, -3, -4, -5, -9* and

-10), 4.75 (br s, 2H, N-H, disappears upon addition of IfeO), 3.5 (m, 1H,

H a t C-6), 2.9 (m, 1H, H a t C -l), and 2 .4 (m, 2H, H a t C- 8). The structure

of the hydrazone was established by measurement of its exact mass and by reaction with tosyl chloride in pyridine to yield tosylhydrazone 12.

Hydrazone 6£ reacts vith potassium t-butoxlde in dimethylsulfoxide to give pyrazoline 64 in 48$ yield (Equation JO ); the two minor hydrocarbon pro

ducts were not identified.

NH2NH2

II CH3SCH3 &

Semicarbazone \ also reacts vith excess potassium hydroxide in ethylene glycol at 200° to give pyrazoline 64_ (54$); the two minor volatile

components were not Isolated (Equation 7l)»

0 II XNNHCNH2

(71) HOCHgCHsOH

Formation of pyrazoline 64 from ketone 1 under Wolff-Kishner reaction conditions may involve in itial generation of hydrazone tautomer 67 by

\ 6 3 either (l) deprotonation of hydrazone 6£ (as starting compound or as formed

in situ), isomerization to 66, and reprotonation (Equation 72), or by (2)

EH EH

£ £L

saponification of the semicarbazone (Equation 73) followed by tautomeriza-

0 II 0

66 ♦ 67 (7 3 )

tion to 66 and reprotonatlon. In either sequence, reprotonation of the hydrazone anion should occur from the less hindered anti-side to give the sjjnn-substituted imide intermediate 67.

Deprotonation of 67 by base produces anion 68 which may (l) lose nitrogen to form the bicyclo[lf.2.2]deca-2,4,9-trien-7-yl carbanion (6^), which rearranges or reprotonates to hydrocarbon products, or (2) attach the diene bridge intramole cularly to form ally lie onion 70 (Equation 7^-).

Protonation of anion 70^ at C-5 or C-7 produces either pyrazoline 6]+ or H ^ - N a N=N—t^ V H very & minor (7k) BH N^najor

H 6k

12. its isomer Jl. Protonation occurs more readily from the stericalXy less hindered side of the allyl anion to form 6k,

In order to learn more ah out the reactions of hydrazines with 1, bicyclo[lf.2.2]deca-2,4,9-trien-7-one methylhydrazone (72) vaB prepared from ketone 1L and methylhydrazine at 75° (Equation 75) • Methylhydrazone 72 has

In fra re d absorption a t 3550 cm"1, nmr a b so rp tio n s a t A 5*75 (®, 6h , H a t

C-2, -3# -5» m9t and -10), 3*9 (m> 1H, N-H, disappears upon addition o f D2O), 3.35 (quintet, 1H, H a t C-6), 2 .8 (d on m, JfH, methyl C-H and H a t C -l), and 2.U (m, 2H, H a t C- 8) and a proper exact mass (m/e *= 17*0. 65

NH2NHCH3 (75)

When ketone 1_ reactB vith methylhydrazine and potassium hydroxide In ethylene glycol at 200° or In reaction of methylhydrazone 72 and potassium hydroxide under similar conditions, 3-m ethyl- 2, 3*diazatricydo[ 6. 3. 1. 04 , 113- d o d e c a -1 ,5 /9 -trie n e (££> 75^) i s formed (E quation 76). T ric y c lic compound

(76)

KDH

73 has proper mass spectrum (m/e « 174), combustion analysis, and infrared and nmr absorptions; 7g exhibit s nmr absorptions at 6 6.00 (m, 2H, H at C-9, 66 and -1 0 ), 5 . 8O (m, 1H, H a t C -5), 5*36 (m, IE , H a t C -6), 3.82 (in, IE, H

a t C-4), 3.49 (m, 2H, H a t C-8 and - l l ) , 2 .48 (dd, 1H, H a t C-12), 2.10

(m, 2H, H a t C-7 and -1 2 ), and 1.64 (m, 1H, H a t C -7). The nmr s tr u c tu r a l

assignments of jfjJ. agree with the nmr of allylamine 74, a model compound.

^ ------5.3 6 5.13 ^CH2-KHa C = C. H H 6 5.03-"* 6 5*92 l i t

The structure £5 is further substantiated by nmr double irradiation

and europium shift studies. Decoupling of the absorption at 6 3*49 simpli

fies the absorptions at 6 6.00 (to s), 5.36, 3.32, and 2.48. Decoupling

at 6 1.64 simplifies the absorptions at 5*3, 5.36, 3.82, and 2.10. Europium

shift data for 7J. are summarized in Table VI. Europium probably co-ordinates with nitrogen at the 2- or 3 "position in amine 75 and is stericolly directed by N-methyl to lie over C-7 and C-12. As a result the methyl absorption

is the most greatly shifted; resonances for the protons, on c?7, -3 , and

-12 also shift greatly due to their proximity to the europium moiety. The

olefinic protons on C-9, -10, and on C-5, -6 are a ll somewhat more shielded

from the europium conplex and hence shifted to a lesser extent.

Formation of can be explained'via initial deprotonation of methyl hydrazone 72 and subsequent intramolecular nucleophilic attack on the diene bridge to foxm allyl anion 7^ (Equation 77). Protonation from the • . less hindered side leads to 73. T able VI

Eu(Fod)s Induced Chemical Shift Data for Compound

N r

i f 10 73

------NMR, shift In 6 ■ N 'H a t 1 1

K ch mole? Eu(Fod)3 C-9 j -10 -5 -6 -If -8 , -11 -12 >» -7 - 3

036 6.00 5.80 5.36 3.82 3-^9 2.1+8 2.10 1.61+ 2.90

103E 6.25 6.25 5.55 ^.55 lf.30 3 .7 2.75 2.10 3.95

2096 6.50 6.65 5.90 5.50 5.30 1+.0 3.50 2.70 5.30

30% 6.80 7.15 —— —— — 3.25 6.50

Av d&/lO mole? 0.27 0.1*5 0.27 0.81+ 0.90 0.77 0.70 0,80 1 .2 68

CH3

BH 11 (77) 11

Ketone 1 reacts with excess 1,1-dimethylhydrazine to form the expected bicyclo[4.2.2]deca-2,^,9-trien-7-one dimethylhydrazone ( 76, 75%) (Equation

78). Dimethylhydrazone 76 is of proper exact mass (m/e = 188), shows no

N-H stretching by infrared analysis and has nmr absorptions at 6 5*7 (m, 6H,

H at C-2, -3, -5, -9, -10), 3 .b (m, 1H, H a t C -6), 2.7 (m, 3H, H a t

C-l and -8), and 2.3 (d, 6 h, methyl C-H). Reaction of ketone 1, 1,1- dlmethylhydrazine and potassium hydroxide in ethylene glycol at 200° also forms dime thy lhydrazine j6 .

1 76

Reduction of ketone 1 with sodium borohydride in methanol at 0° pro duces blcyclor^.2.21deca-2tUt9-trlen-syn-7-ol (77j 92% yield), mp 35-56°

(Equation 79)* Alcohol 77 gives a proper combustion analysis and mass • * spectrum (m/e = 148), infrared absorption at 355° cm“l and nmr absorptions 69

NaBHi (79) CH30H

at 6 5.0 (m, 6h, H at C-2, -3, -U, -5, -9 , and -10), 3 .9 (m, 1H, H a t C -7),

2,h (in', 1+H> H at C-l, -6, and -8), and 1.9 (s, 1H, -OH, disappears upon addition of DgO). The stereochemistry at C-7 as syn is assigned on the basis of steric factors and by analogy to borohydride reduction of bicyclo- 30 [4.2.1]-nona-2,4,7**trien-9“one to bicyclo[^.2.l]nona-2, k ,7-trlen-syn-

9 -o l.

Alcohol 77 is of interest as a possible source of bicyclo£^.2.2]deca-

2,lt,9~trien-7-yl bromide and its subsequent free radical 78* Reaction of 50 77 vith triphenylphosphine dibromide in dimethylformamide results in pro-

(50 ) (a) G. A. Wiley, R. L. Hershkowitz. B. M. Rein, and B. C. Chung, J . Amer. Chem. S o c., 86, 96h (I96*0j (b) J. P. Schaefer and B. S. Weinberg, J. Org. Chem., 30, 2635 (196565). duction of bicyclo[4.2.2]deca-2,4, 9-trlen-syn-7-yl formate (jg) in 40-45$ yield (Equation 60). Two other products formed could not be identified.

(80)

12.

Formate is of proper mass and spectral properties and is identical with a sample prepared from reaction of alcohol 77 with acetic formic anhydride

(Equation 8l). The nmr of 79 shows absorptions at 6 7.7 (s, 1H, formate

HCO

* (81)

C-H), 5.5 (®, 6h, H at C-2, -3, -4, -5, -9, and -10), 4.8 (m, 1H, H at

C-7), 2.85 (m, 2H, H at C-l and -6), and 2.0 (m, 2H, H at C-8).

Formate 79, probably results via anti-bromide 80 formed in situ (Equa tion 82)} previous work on bicyclic systems has shown that the bromination so reaction occurs with Walden-Inversion. Subsequent nucleophilic attack by dimethylformamide, again with Walden inversion, leads to syn-formate 7g 71

Br HO

(82) ©N(CH3 )g

0 CO II H (CH3 )gNCH HaO -B r”. -(CH3 )gHH ■H®

after hydrolysis of the imminium salt 8l. Formate 79, nay also form directly from alcohol £T via a fornylating agent such as 82 formed In situ from dlmethylformamlde and triphenylphosphlne dibromide.

O-P03 (CH3)gN-C-H, Br® ©

62 72

Photochemical rearrangement of ketone 1 was Investigated for possible facile synthesis of various bicyclic and tricyclic derivatives. Irra diation of ketone JL in acetone through Vycor produces two Isomeric pro- 2 S ducts along with 1 (10/6). The fluxional molecule tricyclo[5-5.2.0 ’ ] - 5 1 deca-3*6-dien-9(l0)-one ( 83) is the major product (68^> yield, Equation -1 31 83). Ketone exhibits infrared carbonyl stretching at 1685 cm” ( l i t

(51) W. von E. Doering, B. M. Ferrier, E. T. Fossel, J. H. Hartenstein, M. Jones, Jr., G. Klumpp, R. M. Rubin, and M. Saunders, Tet., 23, 39^3 (1967).

1685 cm-1), ultraviolet maxima in heptane at 200, 290, 300, 312, and 322

(®max B 7 ,^ 0 0 , 130, 105 , 85 , and 6l) and nmr absorptions at 6 3.8 (m,

H a t C-3, - 1*, -6, and -7 ) and 2 .5 (m, 6 h, H at C-l, -2, -5, -8, and -10).

The nmr of 8^ is temperature dependent) ketone 8^ is identical in all 3 0 respects to an authentic sample prepared by ring expansion of barbaralone s i with diazomethane.

The second irradiation product is tentatively assumed as tricyclo-

[ 5 . 3 .0.02' 10]deca-3,5-dien-8-one (8U, 12?>) (Equation 83). Ketone 8U shows

10 10

hv (83)

a a 8U Infrared carbonyl absorption at 1740 cm”1 typical of cyclopentanones, proper exact mass (m/e *= 146) and nmr absorptions at 6 5.9 (m, 4h, H at

C-3, -4, -5, and -6), 3.3 (b r t , 2H, H a t C -7), 2 .5 (m, 3fl, H a t C-2),

2.0 (m, 2H, H at C-9), and 1.5 («, 2H, H at C-l and -10). Ketone 84 does not form a tosylhydrazone derivative in the expected manner.

Formation of and 84 by photosensitized irradiation of ketone 1 may involve dlradical 8£ (Equation 84). Reaction vith carbonyl group carbon C-7 produces diradical 86 which collapses to ketone 8^ . Reac

tion vith the C-9> -10 monoene bridge forms diradical 87 which may collapse

vith carbonyl migration to ketone 8jf.

Irradiation of ketone 1 in ether with Pyrex optics produces ketone

§2, (W3%) and ketone 8j* (27%). Photochemical rearrangement of 1 using

Michler' a ketone as sensitizer and Pyrex optics also produces ketone 8£

in kk% y ie ld .

Ketone 8j5 reacts with dilute trifluoroacetic acid to produce ketone 1

quantitatively (Equation 85 ). Further, reaction of 83. and tosylhydrazide

H30 © (85)

§2. i

in ethanol with hydrochloric acid catalyst forms tosylhydrazone 12 (68%).

A possible reaction path for the acid-catalyzed rearrangement of 8j5 to 1

is depicted below (Equation 86).

Ketone 8^ is reduced by sodium borohydride in methanol at 0° to

A s l tricyclo[3.3.2.0s'B]deca-3,6-dien-9-ol ( 88, 88%) (Equation 87). A lcohol

88 exhibits a superimposable infrared spectrum with the previously reported

5 1 alcohol, ranr absorptions at 6 3*8 (m, 2H), 3.1 (br t, 2H), 3 .8 (m, 1H,

H at C-9)> 2.3 (% 6h), and 2.0 (s, 1R, hydroxylic OH, Bhift is concentra tion dependent, disappears upon the addition of D 2O) a t k0° and proper 75

OrH OH

(6 6)

-H© U+2 r in g opening

m ss Bpectrum. The nmr of alcohol 86 is temperature dependent; the absorp tion at 6 5*1 shifts to higher field as teiqperature increases (6 if . 65 a t

80°) and to lower field upon cooling (ft 5*51 at -25°). Part of the multi- plet centered at 8 2 .3 also shifts with temperature (toward lower field upon warming, higher field on cooling) hut the complexity of the absorption precludes further analysis.

10 NaBH* 8 CH3OH (87)

68 76

The present dissertation represents a study of synthesis and some of the chemistry of bicyclo[4.2.2]deca-2, h,9-trien-7-one (l) and its deriva tives. Initially, preparation of bicyclo[k. 3.2]undeca-2,1*,8,10-tetraen-

7-one and study of the chemistry of the bicyclo[k.3.2]undeca-2, U, 8, 10- tetraen-7-yl carhonlum ion, carbanion and carbene were a portion of the goals of this research. After this phase of the research had been initia ted, the bicyclic[^. 3.2]tetraenyl system was reported synthesized from methoxy- sa tetraene 37. in essentially the same manner as planned in this laboratory*

(32) (a) Privately communicated from M. J. Goldstein, November 26, 1971. (b) M. J. Goldstein and S. A, Kline, Tet. Letters, IO 89 (1973)•

5 2 Because of this report, continued studies in this area vere abandoned; other aspects of the chemistry of the bicyclic[k.2.2] system vere investigated.

There is much yet to be learned about the bicyclo[^.2.2]trlenyl system.

Examination of the properties of bicyclo[lf.2.2]deca-2,^,9-trien-7-yl car bene, carbonium ion and carbanion should provide further insight into the interconversions and chemistry of these systems. Also of Importance are the synthesis of bicyclo[4.2.23deca-2,U,9-trien-7,8-dione (j>6) and study of its chemistry. Further investigation of the hydrolytic behavior of anti-8-acetoxybicyclo[U.2.2]deca-2,l+,9-trien-7-one ( 26) may provide infor mation toward synthesis of £6. Photochemical rearrangements of diketone 2*6 36 may produce tricyclo[3.3.2.0 ’ ]deca-3>6-dien-9,10-dione, a possible degenerate ketone. Additional future studies include reaction of ketone

1 and diketone £6 with organometallic reagents in efforts to further expand the synthetic potential of the bicyclo[l|-.2.2]trienyl system. SUMMARY

This report represents the study of the synthesis and some of the chemistry of bicyclo[lf.2.2]deca-2,lf,9-trien-7-one (l), 8-ketoblcyclo-

[k.2.2]deca-2jfl+,9_trlen-7-yl carbanion (8), carbene (U2), and carbonium ion (]■*£). Ketone 1 is obtained from ring expansion of bicyclo[l*-.2.1]- nona-2,l*,7-trien-9-one with diazomethanej spiroCbicyclo[lf.2.1]nona-2,4,7" trien-9,21 -oxirane] ( 2 ) is a by-product of ring expansion. Hydrogenation of !L to form bicyclo[4.2.2jdecan-7-one (k) conclusively establishes the structure of 1. Treatment of ketone 1 with deuterium oxide-sodium deuteroxide produces antl-8-deuter lobicycloCk. 2.2]deca-2,4,9-trlen-7-one (g^ which is then transformed to 8,8-dideuteriobicydo[4.2.2]deca-2,4,9-trien-

7-one (l l ) upon longer exposure to the deuteratlng medium.

Reaction of bicyclo[4.2.2]deca-2,^,9-trien-7-one tosylhydrazone (12) with methyllithlum yields bicyclo[4.2,2]deca-2,4>7>9-tetraene (l*f) along with naphthalene and cis -9 j 10-dihydronaphthalene. Ketone IL forms enolate

(3 upon reaction with potassium t-butoxide. Enolate 8^ reacts with acetyl chloride to produce 7-acetoxybicyclo[if.2.2]deca-2,^,7>9-tetraene (lj?) and with trim ethylsilyl chloride to form 7-trjmethylsiloxyblcyclo[^. 2.2]deca-

2,k,7j9-tetraene (2l). Enolate 8^ methylates forming 7-methoxybi cyclo id. 2 .2]deca-2,l+, 7,9-tetraene (17^ Uyfc) and 8,8-dimethylbicyclo[4.2.2]deca-

2,U,9-trien-7-one (19, 26%) in glyme. Methylation of 8^ in hexamethylphosphoramide or dimethylformamide at 0° produces 17 (92%). Upon standing, 8

77 78

rearranges slowly to the anion of p-tetralone and probably the anion of

e l s - 9> 10- d lh y d ro - 2-naphtholj secondary methylation products as a conse

quence of rearrangement are 2-m ethoxy- 3, fr-dihydronaphthalene ( 20) and 2-

methoxynaphthalene. Ketone 1 reacts vith isopropenyl acetate to form 1£

and with pyrrolidine to give 7-pyrrolidinobicyclo[fr. 2 . 2 ]d ec a-2,fr,7,,9-te tra e n e

( l 6). 7-Substltuted tetraenes 15-17 and 21 hydro3yze to ketone 1_. Methoxy-

tetraene 3£ thermally rearranges to naphthalene ( 66$) and 2-methoxynaph-

th a le n e ( 33$ )•

Lead tetraacetate oxidizes ketone 1 to antl- 8-acetoxyblcyclorfr.2.2ldeca-

2,h, 9-trien-7-one (26) quantitatively. A ttested add-catalyzed transester-

ification of 26 with methanol forms syn- and anti- 8-methoxybicyclo[fr. 2 . 2] -

deca-2,fr,9-trien-7-ones (28 and 2 9 ). Bicyclo[fr.2.2]deca-2,fr,9-trien-7, 8-

dione monooxlme ( 35 ) results from reaction of enolate <3vith Isoamyl

nitrite in t-butanol. Ketooxime converts to quinoxallne ;5fr with o- phenylenediamine. Attempts to prepare bicyclo[fr. 2.2]deca-2, b,9-trien-7,8-

dione ( 5 6 ) from failed. Reaction of (3 vith methyl formate produces 8-

fornylbicyclo[fr. 2.2]deca-2,9-trien-7-one ( 38) quantitatively. Treatment

of ;5j3 vith hydrazine gives 3 >fr“diazatricyclo[ 5 . fr.2 . 0a,S]trideca- 2 , 5 >8, 10, 12- pentaene (^ 9 ). 7-Diazobicyclo[4.2.2]deca-2,fr,9-trien-8-one ( 37) form s

from reaction of ^ vith tosylazide and triethylamine.

Diazoketone 37 converts to bicycloHfr-. 2. llnona-2,4.7-trlen-syn-9-

carboxyllc acid (fro) upon photolysis in dloxane-vater. The homogeneity of foO is substantiated by formation of methylbicyclo[fr. 2 . 1 ] nona- 2, fr, 7- t r i e n -

syn-9-carboxylate (frl) from reaction of fro and diazomethane. Decomposition •

of diazoketone ( 3j) vith acetic acid or hydrogen chloride proceeds via 7 9 rearrangement through the 10-ketobicydo[ 5 . 2 . 1]deca-3 »5 >8- t r i e n - 2- y l c a r- bonium ion (47) vith subsequent anion quenching from the lesser hindered

side of 4£ to form exo- 2-acetoxybicyclo[g. 2. 1]deca-3, g ,8- t r i e n - 10-one (44) o r exo- 2-chlorobicyclo[5. 2 . H d e c a -3 .5 . 8- t r l e n - 10-one (g4), respectively.

Silver acetate converts chloride into acetate 44. Chloride 54 hydro- genylyzes to bicyclo[g. 2 . 1]decan- 10-one (gj>) confirming the structural assignment. Acetate 44 hydrogenates to form exo-2-acetoxybicyclo[g.2.1]- decan- 10-one (gO) which upon saponification and oxidation produces bicyclo-

[5.2.1]deca-2,10-dione (g 2 ). Acetate 44 and chloride g4 undergo facile

Cope rearrangem ents farm ing endo- 6- ( c ls -2 1-acetoxyvinyl)-cls-blcyclo[3.3.0*1- o c ta - 3, 7-d ie n - 2-one (gj) and endo- 6- (c is - 2 * -chlorovinyl)-cis-bicy clo [3 • 3 • 0 ] - octa-3*7-dien-2-one (g 8), respectively. Acetate g7 hydrolyzes to endo- 6-

(1'- oxoethyl)-cis-bicyclo[ 3 . 3 . 0] o c ta - 3f7-d ie n - 2-one ( 60).

Attempted Wolff-Kishner reduction of ketone 1, bicyclo[4.2.2]deca-

2,4,9-trien-7-one hydrazone (6^) or the semicarbazone derivative £ produces

2#3-diazatricyclo[6.3.1.04 , 11]dodeca-2,g,9-triene (64). Upon reaction of ketone 1 vith methylhydrazine and potassium hydroxide, 3-®ethyl-2,3-diazatricyclo[6.3.1.04,X1]dodeca-l,g,9-triene (j£) is formed. Sodium borohydrlde reduction of ketone 1 yields bicycloC4.2.2~1deca-2,4,9-trlen-syn-T-ol (jj).

Reaction of 77 with triphenylphosphine dibromide in dimethylformamide pro duces bicyclo[4.2.2ldeca-2,4,9-trien-syn-7-yl formate (79). Photochemical rearrangement of ketone 1_ under either non-sensitized or sensitized con- 2 6 ditions leads to formation of tricyclo[ 3 .3 . 2 .0 * ]deca-3* 6-d ie n - 9 (lO )-one

(djj) as the major product vith tricyclo[ 5 . 3 . 0 , 0^, 10]deca-3i 5 - d ien - 8-one

(84) tentatively assigned as the minor product. Ketone 8j^ re v e rts t o ketone 1 upon treatment vith acid. EXPERIMENTAL

Melting Points. Melting points vere determined using a Thomas Hoover

capillary point apparatus and are uncorrected.

Elemental Analysis. Elemental analyses vere performed by Chemalytics, Inc.,

Tempe, Arizona; Microanalysis, Inc., Vilmington, Delaware; or Galbraith

Laboratories, Inc., Knoxville, Tennessee.

Ultraviolet Spectra. Ultraviolet.spectra vere obtained using a Cary Model lU recording spectrophotometer.

Infrared Spectra. Infrared spectra vere obtained on Perkin Elmer Model

137 or 1*57 recording spectrophotometers. All spectra vere calibrated vith a polystyrene absorption peak at 1601 cm"1.

Nuclear Magnetic Resonance Spectra. Nuclear magnetic resonance spectra vere determined using Varian Associates nuclear magnetic resonance spectro photometers Models A-60, A-60A, and HA-100. Unless noted otherwise, a ll spectra vere measured in chloroform-d or carbon tetrachloride solutions using tetramethylsilane as an internal standard.

Gas Chromatography. Gas chromatography vas performed using a Wilkins

Aerograph Model A-90-C vith a thermal conductivity detector. Column A was composed of 20$ SEr30 on Chromosorb W (0.25" x 12'). Column B consisted of 15$ Carbovax 20M on Chromosorb W (0.25" x 10* )* Column C vas made of 12$ 81 Apiezon J on Chromosorb P (0,125" x 10'). Relative peak areas vere obtained by multiplying peak height by peak vidth at half height.

Preparation of Bicyclo[U.2.1*)nona-2, **, 7-trlen-9-one. Unsnturated ketone se vas prepared according to the method of T. A. Antkowiak in k9-6$% o v e ra ll

yield from cyclooctatetraene. Glc analysis (column A) shoved the product

to be 99+^ pure; ir (neat): 1800 cm "1 (s)j nmr: 6 5.9 (n, 6h, H at C-2,

-5 , -5 t -7 , - 8) ancL 3 .1 (m, 2H, H a t C -l, - 6).

Reaction of BicycloL**, 2. l]nona-2, k, 7-trien-9-one vith Diazomethane.

Alcoholic ethereal diazomethane (600 ml of O .33 M solution, 0.2 mole) vas prepared by charging a flask containing a solution of potassium hydroxide

(120 g) in methanol (300 .ml) - vater (80 ml) and ether (600 ml) vith bis-

(N-methyl-N-nitroso)terephthalimide (70$ suspension in mineral oil) at 0°.

The.flask vas equipped vith non-ground glass takeoff and attached to a receiver cooled in isopropanol/dry ice. The mixture vas gently vanned

and distillation continued until the distillate no longer vas yellov.

The diazomethane solution vas added a ll at once to a solution of ketone

(10.5 Bt 0.°79 mole) in chloroform (80 ml) - methanol ( 1*0 ml) containing

lith iu m c h lo rid e (0 .1 g, 0.002** mole) a t 0°. The m ixture vas sto re d a t 0°

until starting ketone disappeared (ca 3 hr) as evidenced by micro tic

analysis on silica gel G using ether-hexane (2:3) as eluant. Formic acid

(6 ml, O.15 mole) vas carefully added dr op wise (5 min) vith stirring and the mixture extracted vith vater-ether. The aqueous layer vas vashed with e th e r ( 2x) and the combined ether layers vashed vith saturated sodium bicarbonate solution ( 2x), saturated brine solution (lx), and filtered through Drierite. After concentration of the extract under reduced pressure, 82 the oily residue was distilled to yield a water white mixture (ll .5 g> 909&) of bicyclo[l+. 2. 2 ]deea-2,l+,9- tr ie n - 7-one (l) and spiro[bicyclo[l+, 2. 1}nona-

2,l+,7-trien-9,2f-oxirane] (2), bp l+3-l+7° (0.15 mm),' mass spectrum m/e =

11+6 .

Anal. Calcd for C 10H10O: C, 02.16; H, 6. 89.

Found: C, 81.70; H, 6 .7 2 .

Separation, analysis, and isolation of the products by glc (column A) gave epoxide 12 (relative retention time = 1 . 0, 15 - 50 ?6) and ketone 1 ( r e la tive retention time «= 1 . 2, 85 -5096).

Data for epoxide 2: ir (neat): 980 (m), 860 (s), and 7*+5 cm "1 ( s ) j nmr: 6 6.1 (m, 1+H, H at C-2, -3, -*+, -5), 5*55 (d, 2H, H at C-7, - 8) , 3 .0

(s, 2H, H at C-2'), and 2.75 (m, 2H, H at C-l, - 6). Exact mass; calcd

11+6.0732; found 11*6.073^.

Anal. Calcd for C 10H10O: C, 82.16; H, 6. 89.

Found: C, 81.99; H, 6. 88.

Data for ketone 1: ir (neat): 1710 cm - 1 ( s ) ; nmr: 6 5.9 (m, 6H, H a t C-2, -3 , -1+, -5 , -9 , -1 0 ), 3.5 (m, 1H, H a t C- 6), 3.0 (m, 1H, H at C-l), Eft 0H and 2.55 (d with s, 2H, H at C- 8); uv: 202, 258 , 265 , and 300 nm

(®max “ ^ ^ 0 , 3070, 2920, and 373). Exact mass: calcd 11+6.0732; found

11+6.073^.

Anal. Calcd for C3.0H10O: C, 82.16; H, 6. 89.

Found: C, 82.20; H, 6. 83.

Reaction of Bicyclo[l+.2.2]deca-2,l+,9-trien-7-one (l) with Semicarbazide 28 Hydrochloride. The crude reaction mixture of ring expansion of bicycloLl+. 2 . 1]nona- 2,l+,7- t r i e n - 9-one containing ketone 1 (8596) and epoxide J2 (15$) (3.15 Et O.OI85 mole) was dissolved in ethanol (250 ml)-water (20

ml). Semicarbazide hydrochloride (5 g) and sodium acetate (7*5 g) vere

added and the mixture warmed for 1 h r a t 75 • The mixture was concentrated

under reduced pressure to half volume and cooled in ice. The crude semi-

carbazone (3*29 Bt 88$ based on ketone) vas filtered and air dried. Pure bicyclo[l*. 2 . 2]deca-2,l*, 9- t r ie n - 7-one semicarbazone (£) was obtained as white

crystals, mp 199. 5 - 2OO.50 by recrystallization from 50 $ aqueous ethanol

and clarification with Norite. Exact mass: calcd 203.1059; found 203.1061.

A nal. Calcd f o r C 11NX3N3O: C, 65.00; H, 6.1*5*

Pound: C, 61*. 68; H, 6.1*3.

Preparative Isolation of Bieyelo[l*.2.2]deca-2,l*,9-trien-7-one (l). Two methods of Isolation of 1 were developed; method I is superior and vas

used extensively for the remainder of this work.

Method I. The crude oily residue initially obtained after ring expansion with diazomethane was refluxed with Girard's reagent T (ll*.0 g,

0.08 mole) far 1 hr in acetic acid (10 ml), ethanol (60 ml), and water ( 1* ml). The mixture vas cooled to 25° and diluted with water, brine, and

ether. After the ether layer had been separated, the aqueous layer was warmed with concentrated hydrochloric acid (20 ml) to 75° for 15 min. The aqueous mixture vas cooled, extracted with ether, and then reheated. This procedure vas repeated several times and the ethereal extracts vere com bined, washed with aqueous sodium bicarbonate ( 2x), brine (lx), filtered through Drierite, and concentrated under reduced pressure. D istillation of the residue yielded 1 as an oily white solid ( 5.75 gi 50 $), bp 71-73° ( 0 .1 mm). Glc analysis of the product (column A) showed no remaining epoxide 2. 8U

Method II. Crude semicarbazone 2. (3*00 g, 0,015 mole) was dissolved in pyruvic acid (l 6 g) and stirred for 30 hr tinder argon. The reaction mixture was diluted with water (60 ml), neutralized with aqueous sodium bicarbonate and extracted with ether. The ether layer was washed with brine (lx), filtered through D rierite, and concentrated under reduced pressure. Pure ketone 1 was obtained by distillation, bp 83- 86° (0.2 mm), (O.JO g, 23?G); th is compound matched in a ll ways !L as prepared via method I.

Reaction of Bicyclo[h.2.2]deca-2,U,9-trien-7-one (l) with 2,l+-Dinitrophenyl- 28 hydrazine. Ketone 1 (0.21 g, 0.0011+ mole) dissolved in chloroform (10 ml) was mixed with 2,4-dlnitrophenylhydrazine ( 0 . 1+ g) dissolved in concen trated sulfuric acid (2 ml), water (3 ml), and methanol (10 ml), and stirred for 1 hr at 25°. The crude product was filtered and air dried (0.3 g, 6k%).

Pure bicyclo[l+.2,2]deca-2,l+,9-trien-7-one 2,l+-dinitrophenylhydrazone was obtained as bright orange needles, mp 221- 222. 5 ° , from 1:1 methanol- chloroform; mass spectrum m/e = 326; ir (KBr): 1630 (m), 1330 (m), and

1510 cm"1 (m).

Anal. Calcd for CieHnl^O*: C, 58.89; H, 4.32; N, 17.17.

Found: C, 58.64; H, 4.20; N, 17.20.

Reaction of BicycloL4.2.2]deca-2,4,9-trien-7-one (l) with Hydroxylamlne 28 Hydrochloride. Ketone 1 (l.O g, O.OO69 mole) and hydroxylamlne hydro chloride (1.39 8* 0.020 mole) were dissolved in methanol (20 ml). Potassium carbonate ( 1 .3 9 8/ 0.010 mole) in water (10 ml) was added and the mixture was stirred for 18 hr at 25°. Water (75 ml) was added and the mixture was * extracted with ether (3x). The ether layer was washed with brine, filtered through Drierite and concentrated under reduced pressure to produce a yellow oil (1.0 g, 91$). The oil was crystallized by solution In ether (8 ml) - hexane ( l 6 ml) and storage at -20°. Pure bicyclo[^.2.2]deca-2,1+, 9-trien-T- one oxime was obtained as white crystals, 115 131- 132°, mass spectrum m/e a l 6l | i r (KBr pe ll e t ) : 3300 (s ) and 1660 cm "1 (v )j nmr: 6 5.8 (m, 6h, H a t

C-2, -3, -It, -3, -9, -10), 3.9 (dd, IB, H at C- 6), 3*0 (m, IB, H a t C -l), and 2 .6 (m, 2H, H a t C- 8).

Anal. Calcd for CibHnNO: C, 7k.51} H, 6. 88; N, 8. 69.

Found: C, 7^.30; H, 7*05; N, 8.5k.

Catalytic Hydrogenation of Bicyclo[lt. 2.2]deca-2,4,9-trlen-7-one (l). A mixture of ketone 1 (2.00 g, O.OI36 mole) and 5 % palladium on carbon ( 0 .2 g) in ethanol (150 ml) was placed in a Parr hydrogenator; in 30 min uptake of hydrogen was complete. The reaction mixture was filtered and concen trated under reduced pressure; the residue was dissolved in ether. The ethereal solution was washed with brine, filtered through Drierite, and reconcentrated tinder reduced pressure. The resultant bicyclot^.2.2]decan-

7-one, (4p 1.97 8t 95$)* was purified by sublimation and crystallization from pentane to produce white crystals, mp 155-157°* Glc analysis (column A) showed th e product t o be one component; i r (KBr p e ll e t ) : 1720 cm"1; nmr:

6 2.3 (doublet imposed on m, IfH, H at C-l, - 6, - 8), and 1 .7 (m, 12H, H a t

0 C-2, -3, -U, -5, -9, -10). Exact mass: calcd 132.1201; found 132.1201;.

23 Reaction of Bicyclo[U.2.2]decan-7-one (k) with 2,U-Dlnitrophenylhydrazlne.

Saturated ketone 4 ( 0 .3 g, 0.0033 mole) was reacted with excess 2,l;-dlnitrophenylhydrazine in ethanol with sulfuric acid catalyst as previously des cribed. The crude orange product (0.60 g, 35$) on recrystallization from 86

ethanol produced pure bicyclo[4.2.2]decan-7-one 2,4-dinitrophenylhydrazone,

mp 179.5-181°, mass spectrum m/e = 332) ir (KBr): 1650 (s), lM)0 (m),

1350 (s), 1080 (m), 9^0 (m), and 830 cm"1 (m).

Anal. Calcd for C 16H20N4 O4 : C, 57.82) H, 6.06) N, 16.86.

Found: C, 57.79) H, 5.96) N, 16.57.

28 Reaction of Blcyclo[^.2.2]decan-7-one (ji) ylth Semicarbazide Hydrochloride.

Saturated ketone U, (0,70 g, 0.001)6 mole) in ethanol (12 ml) - vater (4 ml)

vas mixed vith semicarbazide hydrochloride (l g) and sodium acetate (1.5 g),

varmed to 75° and diluted vith vater (50 ml). After cooling the mixture to ft O / ® 0°, the crude product vas filtered and air dried, mp 208-210 (lit mp 205 -

207°) (O.57 g, 60$). Recrystallization from 50^ aqueous ethanol produced

pure bicycloL4.2.2]decan-7-one semlcarbazone (jj) as vhite crystals, mp 220-

222°) ir (KBr): 3700 (s), 3400 (e)> and 1710 cm"1 (s). Exact mass: calcd

209.1528) found 209.1531.

Anal. Calcd for C 11H19N3O: C, 63.13) H, 9.15) N, 20.08.

Found: C, 62.99) H, 9.19) N, 20.32.

Catalytic Hydrogenation of Bicyclo[4.2.1]nona-2,4,7-trien-9-one. Unsatura-

ted ketone (l.l6 g, 0.00879 mole) in ethanol (100 ml) vith 5 % Pd on carbon

(0.05 g) vas hydrogenated in a Farr apparatus until theoretical hydrogen

uptake (2 h r). Workup as before produced I .03 g of crude product (85$ ).

Sublimation of the material vith subsequent crystallization frcm pentane

produced pure bicyclo[4.2.1]nonan-9-one (6) as vhite crystals, mp 98-101? s& (lit mp 109- m 0 ). Glc analysis (column A) shoved the product as one 29 component) ir (KBr) p e lle t: 1740 cm" 1 ( l i t 1737 cm"1)) nmr: 6 1.55 (®

* superimposed on m). Exact mass: calcd138.101)6) found 138.1045* Reaction of Bicydo[U.2.1]nonan-9-one ( 6) with Diazomethane. Alcoholic ethereal diazomethane (50 o l, 0.33 Mj 0,015 mole) as previously prepared vas added at 0° to saturated ketone 6 (0.5 g, O.OO36 mole) dissolved in e th e r (6 ml) - methanol (l ml). After 5 days formic acid vas added and the mixture vas vashed vith aqueous sodium bicarbonate and brine, and filtered through D rlerlte. Analysis of the reaction mixture by glc (column A) shoved starting ketone 6 (relative retention time » 1. 0 , r e la tiv e a re a «

10.0 ) and b ic y c lo [^ . 2 . 2]decan- 7-one (jj^ relative retention time = 1 . 75 , relative area = 1.0). The product ketone ^ vas isolated by preparative g lc and p o ssesses th e same s p e c tra l p ro p e rtie s a s th e compound prepared by catalytic hydrogenation of bicyclo[^. 2 . 2]deca-2, ^ , 9- tr ie n - 7-one ( l ) .

Base-Catalyzed Mono- and Dldeuteratlon of Blcyclo[U. 2.2]deca-2, k, 9-trlen-7- one (l). Ketone 1 ( 5 0 mg) vas dissolved in carbon tetrachloride ( 0 .5 ml) containing Vf> TM3, and deuterium oxide (3 drops) containing sodium hydride

(57$ suspension in mineral oil, 5 grains) vas added. The reaction vas run in an nmr tube and mixed by continual tumbling at 25 ° j reaction progress vas monitored by nmr analysis examining the absorption at 6 2.55 for peak and integration disappearance. After 12 hr, half of the organic phase vas removed, dried vith anhydrous potassium carbonate, and concentrated under reduced pressure to provide anti-8-deuteriobicyclo[^.2.2]deca-2,U,9-trien-

7-one (& 25 mg)> nmr: a 5.9 (m, 6h, H at C-2, -3, -»+, -5, -9, -10), 3.5

(m, IB, H at C-6), 3.0 (m, 1H, H at C-l), and 2.55 (a, H at C-0).

Exact mass: calcd l>f7.079^f found lVf.0791.

The remaining organic layer vas tumbled continually at 25° -an addi tio n a l 8 .5 days until complete disappearance of the methylene absorption vas observed. The aqueous layer vas removed; the organic layer vas worked up as above to yield 8, 8-dideuteriobicyclo£lf. 2 . 2]d e c a -2 ,Jf,9- t r i e n - 7-one

(ILL, 25 mg)| nmr: ft 5 .9 (m, 6h, H at C-2, - 5 , -If, - 5 , -9 , - 1 0 ), 3^5 (m,

2H, H a t C-6 ) , and 3 .0 (m, 1H, H a t C -l).

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) with Potassium t-

Butoxide and Deuterium Oxide. Ketone IL (l.O g, O.OO 685 mole) was added to a solution of potassium t-butoxide ( 2 .5 0 g, 0.022 mole) in dry hexamethylphosphoramide (50 ml) at 0-5° and stirred for 4 min. Deuterium oxide

(5 ml) was added and stirring continued for an additional If min. Boron trifluoride etherate was then slowly added until the reaction mixture was slightly acidic. Water (100 ml) was added and the mixture was extracted with ether (If x 50 mi). The ether layer was washed with water (3x) and saturated brine. Filtration through Drierite, concentration under reduced pressure, and distillation yielded 8,8-dideuteriobicyclo[U.2.2]deca-2,4,9- trien-7-one (rL, O .75 g , 75 %), bp 72-76° (0.1 mm). The product, on the basis of its nmr, ir, and glc analysis, vas identical to the previously prepared ketone.

Reaction of Bicyclo[lf.2.2]deca-2,Jf,9-trien-7-one (jl) with Potassium t-

Butoxide and Water in Dimethylformamide. Ketone 1 (0.15 g, 0.001 mole) containing naphthalene ( 0.13 g , 0 .0 0 1 mole) as an internal standard was dissolved in dry dimethylformamide (5 ml) and added to a solution of potas sium t-butoxide ( 0 .2 2 g , 0.002 mole) in dimethylformamide (5 m l) a t 0° and the mixture was stirred for 0 .5 hr. The reaction mixture vas poured into

• * w ater (50 ml) and neutralized with 3N hydrochloric acid. The aqueous mixture vas extracted with ether ( 3x); the comb ined organic extract vas washed with water (3x), aqueous sodium bicarbonate, and saturated brine. Filtration

through D rierite and concentration under reduced pressure yielded 0.25 S

(92^) of a mixture composed of starting ketonel and naphthalene by glo

analysis (column A). Nmr integral analysis of the product mixture showed

the ratio of naphthalene:ketone to be 1. 0 ; 0 . 92.

Reaction of Bicyclo[4.2.2]deca-2,lf,9-trien-7-one (l) with Tosylhydrazide.

Ketone 1 (l.OO g, O.OO 69 mole) in ethanol (25 ml) waB mixed with a solution

of tosylhydrazide ( 1.60 g, 0.0100 mole) in ethanol (25 ml) containing con

centrated hydrochloric acid (l drop) for 5 hr at 25°. The solution was

reduced to half volume under reduced pressure and cooled to -20°. The pro

duct was filtered and the filtrate vas concentrated; the total yield of

derivative was 1.66 g (77^). Recrystallization from ethanol produced bicyclo[U.2.2]deca-2,4,9-trien-7-one tosylhydrazone ( 12) aB white crystals,

mp 156 -156 °, masB spectrum m/e « $lkf ir (KBr pellet): 3^50 (w), 3250 (m),

2950 (m), 16U0 (m), and U90 cm "1 (s); nmr: 5 7.52 (broad s, 1H, N-H),

7.52 (AB, aromatic C-H), 5*9 (m, 6h, H at C-2, -3, -If, -5, -9, -10),

3.5 (quintet, 1H, H at C- 6), 2 .9 (m, 1H, H a t C -l), 2 .5 (m, 2H, H a t C- 8),

and 2. If5 (s, 3H, methyl C-&).

A nal. Calcd f o r Ci 7HieN2Q2S: C, 6I+.9U; H, 5.77; N, 8.91.

Found: C, 6If.8If; H, 5-7^; N, 8.73.

Reaction of Bicyclo[4.2.2]deca-2,lf,9-trien-7-one (l) with Benzenesulforyl- hydrazlde. Ketone JL (l.lfO g, 0.0105 mole) in ethanol (50 ml) was combined with benzenesulfonylhydrazide (2.3*f g, O.OI 36 mole) in ethanol (50 ml)

containing concentrated hydrochloric acid (l drop) and the mixture vas stirred overnight at 25°. Subsequent removal of the solvent under reduced 90 pressure, dissolution of the residue in methylene chloride (20 ml) - hexane

(20 ml) and storage at - 20° provided vhite crystals of bicyclo[ 4 . 2 . 2 ]deca-

« 2,4,9-trien-7-one benzenesulfonylhydrazone (] 2.70 g, 85^ ) , up 62- 65 °} ir (KBr pellet): 3550 (w), 3*+50 (m), 3050 (v), 2950 (v), 161*0 (v), and

1190 cm *1 ( s ) | nmr: 6 7.90 (m, 2H, o rth o arom atic C-K), 7.55 (m, 3H, m eta, p a ra arom atic C-H), 5.70 (m, 6h, H at C-2, -3, -If, - 5 , -9, -10), 3 .5

(q u in te t, 1H, H a t C- 6 ), 2.9 (m, Ifl, H at C-l), and 2.5 (m, 2H, H at C- 8).

Anal. Calcd for CieHieNaOgS: N, 9*52.

Found: N, 9*05.

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one Tosylhydrazone ( 12 ) w ith

3 3 Methylllthivtm. Tosylhydrazone 12 (200 mg, 0.64 mmol) vas suspended in hexane (5 nil) and the system vas flushed vlth argon at 0°. Methyllithium

(2.0 ml, 1.45 Mj 2.9 mmol) vas added slowly, the system vas warmed to 25°, and the reaction mixture vas stirred 3 hr. Water (3 ml) vas added dropvise, the layers were separated, and the water layer vas vashed with ether

(2x). The combined organic layers vere vashed with brine, filtered through Drierite, and carefully concentrated under reduced pressure. The residue (72 mg, 84%) consisted of five components (glc analysis, column A); the three major components ( 98$ of the mixture) vere identified as jcis- 9, 10- dihydronaphthalene (relative retention time » 1. 0, relative area » 1 . 0 ),

* bicyclo[4.2.2]deca-2,4,7,9-tetraene (14, relative retention time = 1.14, relative area <= 66), and naphthalene (relative retention time = 1 . 50 , r e l a tive area = 3*6). Preparative glc (column A) provided pure samples of each compound} retention times and spectral properties of each compound matched 91 34 those of authentic samples; nmr of lk: 6 5.8 (m, 8H, H at C-2, -3, -1+,

-5# -It S t -9f -10)> ana 3.15 (m, 2H, H at C-l, - 6 ).

Reaction of Bicyclo[U.2.2]deca-2,U,9-trien-7-one (l) with Isopropenyl

Acetate. Ketone 1 (0.50 g, O.OO 3I+ mole) was dissolved in isopropenyl ace t a t e (13 ml) containing a trace of £-toluenesulfonic acid and the mixture was refluxed for 60 hr. Potassium carbonate was added, the excess solvent was removed under reduced pressure, and the crude residue was distilled, bp 78-79° (0»05 mm). The distillate (O .55 St 86^) contained only one peak as evidenced by glc analysis (column A); preparative glc was used to purify the 7-acetoxybicyclo[4.2.2]deca-2,h, 7>9-tetraene ( 15 ); ir (neat): 1760

( b ) and 1210 cm- 1 ( s ) ; nmr: • 6 3*85 (m, 7H, H at C-2, -3, -U, -3, - 8 , -9*

-1 0 ), 3.23 (m, 2H, H a t C -l, - 6), and 2.03 ( b, 3H, methyl C-H).

Anal, baled for CigH^O^: C, 76.57; H, 6.^3.

Found: C, 76.62; H, 6.35-

Reaction of Blcyclo[fr.2.2]deca-2,k,9-trien-7-one (l) with Potassium t-

Butoxide and Acetyl Chloride in Glyme. Ketone 1 (0.10 g, 0.0007 mole) was — n r r nnm i~n~if~ i~ i i~ t~\ Of i~ i~n~ t~~ 1—1 < ~ i 1— 1— 1 —1~ r dissolved in dry glyme (3 ml) at 25°. PotasBium t-butoxide (0,22 g, 0.002 mole) vas added a ll at once and the resulting brown slurry vas stirred rapidly for lf-5 min. Acetyl chloride (0.l6 ml, 0.002 mole) vas added and stirring of the mixture vas continued for 5 min. Potassium carbonate

(0 .2 g) vas added, the solvent vas removed under reduced pressure, and the residue vas dissolved in ether (15 ml). The ethereal layer vas filtered to remove suspended solid and concentrated under reduced pressure. Glc analysis (column A) of the yellow oily residue (0.12 g) revealed a three 92 component mixture* unidentified impurity (relative retention time *= 1. 0 , relative area Jf b 9 ), starting ketone 1 (relative retention time «= 1 . 6, relative area $ ** 8), and 7-acet oxybicyclo[h. 2. 2 ]deca-2, k,7,9-tetraene (l^ relative retention time «= 2.2, relative area % = 83). Preparative glc pro vided pure samples of the products vhose spectral properties matched those of authentic samples.

Reaction of 7-Acetoxyblcyclo[fr.2.2]deca-2,lf,7j9-tetraene (ljj) with 3N

Hydrochloric Acid. Acetoxytetraene 15 (0.20 g, 0.0011 mole) vas dissolved

In hexamethylphosphoramlde (3 ml); hydrochloric acid ( 3N) vas added and the solution vas stirred overnight at 25°. The reaction mixture vas poured into water (30 ml) and the. resultant suspension extracted with ether ( 3x ).

The conibined ether layers vere vashed with water (3x), aqueous sodium ■bi carbonate, and saturated brine. Filtration through Brierite and concen tration wider reduced pressure yielded an oil ( 0. l 6 g) which was shown to be a 1:19 mixture of starting acetate 1^ and bicyclo[U, 2 . 2]d eca-2,U,9- trien-7-one (l) by nmr and glc (column A) analysis.

Reaction of Bicyclo[h.2.2]deca-2,l;,9-trien-7-one (l) with Pyrrolidine.

Ketone 1 (0.16 g, 0.0011 mole) and pyrrolidine (0.16 g, 0.0022 mole) were dissolved in dry benzene (10 ml) containing several grains of ^toluenesulfonic acid. The reaction mixture was refluxed for 12 hr making use of a

Dean Stark water separator. The dark red-brown solution vas concentrated in vacuo to produce a dark brown residue (0.22 g). After storage under reduced pressure for several hours, the highly water sensitive product was transferred to an nmr tube in carbon tetrachloride under argon. Nmr analysis 93 showed that T-pyrrolidincfbicyclop. 2.2]deca-2, h,7,9-tetraene (l 6, ca 9036) had formed} starting ketone and benzene vere the impurities} nmr; 6 5*9

(m, 6h, H at C-2, -3, -4, -5# -9# -10), 4.15 (dd, 1H, H at C-8), 3 .4 (m,

2H, H a t C -l, - 6), 3-0 (m, 4H, -H-CHt 2-C ), and I .85 (m, 4h, -N-C-CH 2-). The sensitivity of the product 16 precluded ir or conibustion analysis} upon standing in a nmr tube for one day complete hydrolysis of the enamine to the starting ketone jL and pyrrolidine had occurred. Exact mass: calcd 199.1361} found 199.1359.

Reaction of T-Pyrrolldln6blcyclo[4.2.2]deca-2,4,7,9-tetraene (l^) with

3N Hydrochloric Acid. Enamine 1 6 dissolved in carbon tetrachloride con- talnlng 1$ TMS vas swirled with hydrochloric acid (3N, 3 drops) for 15 tain at 25°. The aqueous layer was removed and the organic layer dried over anhydrous potassium carbonate. The solution on analysis by nmr and glc

(column A) was found to contain bicyclo[4.2.2jdeca-2,4,9-trien-7-one (l) exclusively.

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) with Potassium t-^

Butoxide and Methyl Fluorosulfonate in Hexamethylphosphoramide. Ketone 1

(O.5 O g, 0.0034 mole) was added to a solution of potassium t-butoxlde

(1.25 g, 0.011 mole) in dried hexamethylphosphoramide (30 ml) a t 0- 5 ° under argon and the solution was stirred for 4 min. Methyl fluorosulfonate (1.2 ml, 1.85 g, 0.016 mole) vas added all at once and stirring of the mixture vas continued for 4 min. The reaction mixture was then quenched with aqueous sodium bicarbonate (150 ml) and the aqueous layer vashed with ether

(4x). The combined ethereal layers were vashed with aqueous sodium bicar- b o rn te ( 2x), water ( 2x), saturated brine (lx), and filtered through Drierite. Concentration under reduced pressure yielded a crude yellow Oil (0,54 g,

99%) which contained five components hy glc analysis (columns A and c).

* The major product was 7-methoxybicyclo[4. 2.23deca-2,4,7,9-tetraene (l^,

relative retention time = 1 . 0 ); other products vere ketone 1 (relative

retention time = l.l), 8,8-dimethylbicyclo[4.2.2]deca-2,4,9-trien-7-one

( 19; relative retention time «= 1 . 2 ), 2-methoxy-3,4-dihydronaphthalene

(relative retention time = 1.4), and 2 - met h oxy naphtha le ne (relativ e reten

tion time b 1.6) in the percent composition shown in Table VII. Analogous

results vere obtained using dimethylformamide as solvent (see Table l).

Pure methoxybetraene 17, vas collected by preparative glcj ir (neat):

1670 (m), 1620 (v), 1210 (s), and 830 cm '1 ( s ) ; nmr: 6 3*89 (m, 6h, H a t

C-2, -3, -4, -5, -9t -10), 4.50 (dd, IE, H at C-8), 3.40 (s, 3H, methyl

C-H), and 3*20 (m, 2H, H at C-l, -6). Exact mass; calcd 160.0888; found 160.0886.

Anal. Calcd for C 11H12O: C, 82.46; H, 7.55.

Pound: C, 82.29; H, 7.74.

Reactions vere run varying the contact time of ketone 1_ with potassium t-butoxide before quenching with methyl fluorosulfonate; the product dis tribution for base times of 14 min, 30 min, 8 hr, and 24.5 hr are sum marized in Table, I.

* Reaction of p-Tetralone with Potassium t-Butoxide and Dimethyl Sulfate in pimethylformflmide. p-Tetralone ( 0 .5 8 g, 0.004 mole) vas dissolved in dry dimethylformamide (10 ml) and treated with potassium t-butoxide (0.35 6*

0.005 mole) dissolved in dimethylformamide (5 m l) f o r 15 min at 0°.

Dimethyl sulfate (O .5 8 g , 0,005 mole) vas added and the mixture vas stirred 95

Table VH

Product Distribution from Reaction of Bicyclo[U. 2.2]deca-2, 4,9-trien-7-one

(l) with Potassium t-Butoxide and Methyl Fluorosulfonate in

Hexamethylphosphoramide

^ Product Percentage ■■■ ^

Trial. il i 12. 00r’°°H3 CO'00"3

1 95.0 4 .0 1 .0 --- —

2 92.0 5.0 1.5 — 1.5

3 91.0 3 .0 2 .9 — 3 .1

4 90.0 1.5 6 .1 1 .7 1 .0

5 93.0 1 .0 3.0 1.0 2 .0

6 92.0 1 .0 5.1 0.7 1 .2

7 93.0 , 2 .3 1 .8 1 .1 1 .8

Average 92.2 2.5 3.0 0.6 1.5 fo r 10 min. The mixture vas poured into aqueous sodium bicarbonate (125 ml) and the aqueous layer vas extracted vith ether (3x). The combined ethereal layer vas vashed vith vater and saturated brine, filtered through Brierite, and concentrated under reduced pressure. D istillation of the residue pro duced a clear liquid (0.1*4 g), bp ll*4° (11 mm). Glc analysis (column A) shoved the product to be a mixture containing 0-tetralone (relative retention time « 1 . 0, relative area $ » 5 . 0 ), 2-methoxy- 3, l*-dihydronaph- th a le n e ( 20, relative retention time = 1 . 21, relative area ** overall y ie ld ■= 65 #) and an unidentified component (relative retention time = I. 65 , relative area % «= l) of mass m/e « 172 representing a dimethylation pro d u ct.

Pure 2-methoxy-3,U-dihydronaphthalene (20) vas collected by preparative glc; ir (neat): 1640 cm-1 (m); nmr: 6 6 .9 (m, 4h, arom atic C-H), 5*5

(s, 1H, H at C-l), 3.6B (a, 3H, methyl C-H), 2.9 (m, 2H, H at C-4), and

2.1*0 (m, 2H, H at C-3). Exact mass: calcd 160.0888; found 160.0890.

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) vith Potassium t-

Butoxlde and Methyl Fluprosulfonate in Glyme. Ketone 1 (0.10 g, O.OOO 69 mole) vas dissolved in dry glyme (5 ml) and potassium t-butoxide (Table

VIII) vas added at 25°. After stirring the solution 4 min, methyl fluoro sulfonate (Table VXIX) vas added a ll at once and the mixture stirred an * additional minute. After the solvent had been removed under reduced pres sure, the residue vas dissolved in chloroform and analyzed by glc (column

A). The product mixture contained 7-met hoxyb icy clo [U. 2. 2^de ca-2> 1*, 7> 9-tetra ene (IT, relative retention time «= 1.0), ketone 1 (relative retention time « Table VIII

Product Distribution from Reaction of Bicydo[4.2.2]deca-2,4,9-trien-T-one

(l) vith Potassium t-Butoxide and Methyl Fluorosulfonate in Glyme

Exper Potassium CH3OSQ2F ■ Product Percentage ------s iment t-Butoxide Used Used Yield® 3 1 1 18 19

1 0.10 g, 0.0009 nole 0.10 g, 0.0009 mole 0.110 g 29.0 23.0 6 .0 — (100?)

2 0.25 g* 0*0022 mole 0.25 Bt 0.0022 mole 0.100 g 42.9 10.2 ~ 1 26.0 (9696)

3 0.25 61 0.0022 mole 0.25 Bt 0.0022 mole 0.110 g 45.0 9.5 ~ 1 24.0 (10096)

4 0.25 Bt 0.0022 mole 0.25 g, 0.0022 mole 0.10 g 40.9 10.6 ~ 1 28.1 i1 (9696)

Percent yield calculated on theoretical amount of monomethylation. 9 8

1.15), 8-methylbicyclo[4.2.2]deca-2, b , 9-trien-T-one (18, relative retention tim e t= 1.13), and 8,8-dimethylbicyclo[k.2,2]deca-2,k,9-trien-7-one (1%, relative retention time = 1.39) as well as several unidentified components of longer retention times. Product analysis results are shown in Table

VIII.

Pure dimethylketone 19 was obtained by preparative glc; lj^was unstable upon standing and an analytical sample could not be prepared; ir (neat):

1700 (s), 1380 (m), 1370 (m), and 1100 cm"1 (m); nmr: 6 5.9 (m, 6H, H at

C-2, -3, -U, -5, -9, -10), 3.5 (m, 1H, H at C-6), 2.6 (m, 1H, H at C-l), and 1.2 (dy 6 h, methyl C-H). Exact mass: calcd rrJ+.lOlfk; found 17^.10^1.

Mass spectral analysis of ketone 1 as preparatively collected by glc from the reaction mixture indicated the presence of methylketone 18^ m/e =

160. The amount of 18 present was estimated by comparison of parent peaks of ketone 1 and 18 in the mass spectrum.

Reaction of 7-Metho 3ybicyclo[k,2.23deca-2,k, 7,9-tetraene (17) with Hydro chloric Acid. Methoxytetraene 17 (0.07 g, 0.000^3 mole) was dissolved in chloroform-d ( 0 .5 ml) containing 1% TMS and naphthalene (ca 0.11 g) aB internal standards. Initial nmr analysis showed an aromatic:olefinic proton ratio of 1.0:0.82. The solution was treated with hydrochloric acid (3N,

0.25 ml) and mixed continuously for 1 hr at 25°. The aqueous layer was

» removed and the organic layer dried over anhydrous potassium carbonate.

The product mixture was found to be exclusively naphthalene and bicydo-

[k.2.2]deca-2,k,9-trien-7-one (l) by nmr and glc (column A) analysis; nmr analysis showed the aromatic:olefinic proton ratio to be 1 . 0 : 0 . 83, in d i

cating essentially quantitative formation of ketone 1. 99

Reaction of Bicyclo[U.2.2]deca-2, h,9-trien-T-one (l) vith Potassium t-

Butoxlde and Trimethylsllyl Chloride in Olyme. Ketone 1 (0.292 g, 0.002

mole) vas dissolved in dried glyme (15 ml) and potassium t-butoxide (0.9 g,

0.008 mole) vas added all at once. After stirring the solution for 3 min,

trlm ethylsilyl chloride (1.1 g, 0.010 mole) vas added and the mixture vas

stirred an additional 5 min. The solvent vas removed under reduced pres

sure and the residue distilled to provide a pale yellow oil, bp 65 - 67°

(0.05 mm), (0.33 g, 7Qfi). 01c analysis (column A) shoved the distillate to be a mixture of 7-trim ethyIsiloxybicyclop. 2.2]deca-2, 1+, 7,9~tetraene

(21; relative retention time = lA , relative area = 17, overall yield 72^)

and starting.ketone 1_ (relative retention time = 1,0, relative area = 1.0),

Product 21 hydrolyzed on standing only a few hours in the atmosphere. An

analytical sample of the product could not be prepared; ir (neat): 1660

(m), 1200 (s), 9^0 (s), and 81*0 cm *1 ( b ); nmr: 6 5*9 (m, 6H, H at C-2,

-3, A , -5, -9, -10), 1*.78 (dd, 1H, H at C- 8), 3.18 (m, 2H, H a t C -l, - 6),

and 0.11 (s, 9H, methyl C-H). Exact mass; calcd 218.1127; found 218.1123.

Thermal Rearrangement of 7-Methoxybicydo[lf.2.2]deca-2A,7, 9-tetraene (lj ).

Method.A. A solution of 7-methoxyblcycloA«2.2Jdeca-2A,7,9-tetraene

(17; 0.25 g, 0. 001U mole) in dry hexamethylphosphoramide (3 ml) vas heated

for 0.5 hr at 200°. After cooling to 25°, the mixture vas poured into w ater (35 ml) containing aqueous sodium bicarbonate (15 ml), and extracted with ether (3x). The ethereal extracts were combined, vashed vith aqueous

sodium bicarbonate (lx), water (2x), and saturated brine (ix). After filtra tion through Drierite, the solution vas concentrated under reduced pressure to give a mixture (0.2** g) by glc analysis (column A) containing three 1 0 0

components corresponding in retention time to naphthalene (relative reten tion time = 1.0, relative area « 1.7)# 7-nethoxytetraene (relative retention time = 1.5# relative area = 7.0), and 2-methoxynaphthalene (rela tive retention time » 2.5# relative area «= 1.0).

Method B. 7-Methoxyb icyclo[l*,2.2"]deca-2#4,7#9-tetraene (17, 0.15 6#

0.0009 mole) vas placed in a tube, evacuated to a pressure of 0.05 ®»# and

sealed at 25°. The compound vas then heated to 200° for 21 hr, the tube

opened and the product mixture analyzed by glc (column A) and preparative

glc followed by nmr and ir spectral analysis. The mixture consisted

of three major and one minor products: methanol (relative retention time **

0.14), naphthalene (relative retention time = 1.0, relative area = 5*75)#

7-methoxytetraene (relative retention time = 1.5# relative area = 1.0), and 2-methoxynaphthalene (relative retention time ** 2.5# relative area = 2.88).

Preparation of 2-Methoxyjtiapjitha.l^ene. 2-Naphthol (3.4 g# 0.0237 mole) vas dissolved in hexamethylphosphoramlde (20 ml) and sodium hydride ( 1.05 g,

57? suspension, 0.025 mole) vaB added at 25° a ll at once. The mixture vas

stirred for 0.25 hr, methyl iodide (1.5? ®1# 0.025 mole) vas added all at once, and the mixture stirred for 5 niin. The reaction vas quenched vith vater (100 ml) and extracted vith ether (3x). The ether extracts vere vashed vith aqueous sodium bicarbonate (lx), vater (lx), and brine (lx) and filtered through Drier its. After concentrating the mixture under reduced pressure the residue vas clarified vith Norite and recrystallized from ethanol to yield 2-methoxynaphthalene (3.32 g, 89?), up 70-71.5° (reported mp 72°)| ir (KBr): 1480 (m), 1030 (m), 8U0 (m), 820 (m), and 7^5 cm-1 (m);

nmr: fl 7 .7 5 -6 .9 (m, 7H, H a t C -l, -3 , -k, - 5 , -6 , -7 , -8 ) ana 3.7 5 ( s , 3H, methyl C-H).

Beactlon of Bicyclo[4.2.2]deca-2,U,9-trien-7-one (l) with Lead Tetraacetate. 1—i_j-i_r_n-rLn_nji_n_fuijijLinirifirM^if¥~i- ~ ~ — —■— w~ 1 —~—g- n—1 riri ru~. r~> n n nr r n_ri_rr~ — j~u~ _il_i ji_n_r_n..r_r_n_n-fi_r^^-M~rf*^~f Ketone 1 (0.50 g, 0.0031+ mole) and lead tetraacetate (1.5 g, 0.003h mole) vere refluxed in acetic acid (20 ml) for 5 hr. The mixture was poured into v a te r (150 ml), extracted vith ether (3x) and methylene chloride (lx) and

the combined organic extracts vere vashed vith vater (2x), aqueous sodium bicarbonate (2x), and brine (lx). After removal of the solvent under re duced pressure and storage at -20°, the crude product crystallized (0.70 g,

100$); glc analysis (column A) shoved the material to be 99? pure. DistiHa tion of the crude product afforded anti-8-acetoxybicyclof^. 2.2Jdeca-2, k,9- trien-7-one ( 26)* pale yellow crystals, bp,9^-96° (0.01; mm), mp 81-82°;

ir (KBr pellet); 17^0 (s) and 1220 cm-1 (s); nmr: 6 5*9 (w, 6h, H at C-2,

-3, -1*, -5# -9, -10)* 5.35 (o. 3H, H at C-8), 3 .6 (m, 2H, H a t C -l, - 6 ) ,

and 2.0 (s, 3H, methyl C-H). Exact maos: calcd 201|. 0786; found 20U.O783.

Anal. Calcd for C 12H12O3 : C, 70 .6 0 ; H, 3*38*

Found: C, 70 .7 1 j H, 5*67*

Acid-Catalyzed Reaction of anti-8-AcetoxyblcycloCU.2.2ldeca-2.U.9-trien-7-

one ( 26) vith Methanol. Acetoxyketone 26 (0.20 g, 0,0001 mole) in methanol (10 ml) containing 25 grains of £-toluenesulfonlc acid vas refluxed 7 hr.

After the solvent had been removed under reduced pressure, the residue vas dissolved in methylene chloride and vashed vith aqueous sodium bicarbonate.

The solvent vas removed under reduced pressure after filtration through 1 0 2

Drierite to yield a yellow oil (0.18 g, 100$) which was a 93:7 mixture of

isomers (column A ). Pure syn-8-methoxybicyclol4.2.2~)deca-2.4. Q - trle n - 7-o n e

(28) was obtained by preparative glc; ir (neat) 1720 cm"1* nmr: 6 5.8 (m,

6h, H at C-2, -3, -4, -5, -9, -10), 4.05 (dd, 1H, H at C-8), 3 .7 (m, 2H,

H at C-l, -6), and 3*35 (s, 3H, methoxy C-H). Exact mass: calcd 176.0837*

found 176.0835.

Anal. Calcd for Cu£i20a: C, 74.98; H, 6.86,

Pound: C, 75.15* H, 6. 89.

Reaction of syn-8-Methoxyb icyclol.2.21deca-2.4.9-trien-7-one (28) with SB 2,4-Dinltrophenylhydrazine. Methoxyketone 28 (0.10 g, O.OOO 57 mole) was treated with excess 2,4-dinitrophenylhydrazine reagent. The crude yellow product (0.20 g, 100$) was recrystallized from 1;1 ethyl acetate/ethanol to produce pure syn-8-methoxybicyclo[4.2.21deca-2,4t9-trien-7-one 2,4-

dinitrophenylhydrazone, mp 225-226. 5°, mass spectrum m/e *= 356 .

Anal. Calcd for Ci 7H i6H40 s: C, 57.30; H, 4.53; N, 15-72.

Found: C, 57.35; H, 4.51* N, 15.90.

Attempted Acid-Catalyzed Hydrolysis of anti-8-Acetoxybicyclo[4.2.2]deca-

2,4,9-trien-7-one (26) in Dlmethylformamide-Water. Acetoxyketone 26 (0.2 g,

0,001 mole) in water (5 ml) - dimethylformamide (5 ml) containing £-toluene- su lfo n ic a c id (0.01 g) was warmed t o 1 1 0 ° for 8 hr. The mixture was poured into water (50 ml), extracted with ether (3x) and the combined ether layer was washed with water (3x), aqueous sodium bicarbonate and saturated brine.

Filtration through Drier ite and concentration under reduced pressure afforded a yellow oil (O .1 6 g) which was almost exclusively starting ketone 103 26 (85^) by glc and nmr analysis. The minor products (3 peaks by glc)

showed aromatic proton nmr resonance.

Reaction of BlcyclotU.g.23^gca-2yUf9-trlen~T-one (l) with Isoanyl N itrite 37 and Potassium t-Butoxide. Ketone 1 (1.02 g, 0.007 mole) in t-butanol (10

ml) was added to potassium t-butoxide ( 7 .5 g> 0.07 mole) in t-butanol (65

ml) and the solution was stirred for O .75 hr under argon. Isoamyl nitrite

(3*0 Hi) was added and stirring was continued for 1 hr; iBoanyl nitrite

(2.5 ml) was again added and the mixture was stirred for 0.5 hr. The reac

tion mixture was poured into ether-ice vater and the aqueous layer vas

extracted with ether (2x). The aqueous layer vas acidified vith acetic acid

and re-extracted with ether (3x). The latter ethereal layers were vashed with aqueous sodium bicarbonate ( 2x), brine (lx), filtered through Drierite,

concentrated tinder reduced pressure, and finally dried in vacuo overnight to yield the crude product (O .75 g, 6396). Solution in methylene chloride,

clarification with Norite, and recrystallization from 1:2 methylene chloride-

cyclohexane produced pure bicyclo[4.2.2]deca-2,4,9-trien-7,8-dione mono-

oxime (22), a yellow powder, mp 178-178.5°; ir (KBr): 3300 (s), 1710 (s), and 1690 cm"1 (s); nmr: 6 5.9 (m, 6h, H at C-2, - 3, -4, -5, -9, -10), 4.3

(dd, 1H, H at C-6), and 3.7 (m, H at C-l). Exact mass; calcd 175.0633* found 175.0636. '

A nal. Calcd f o r CioHbNO^: C, 68. 36; H, 5*18.

Found: C, 68. 30, H, 5-30.

Reaction of Bicyclo[4.2.2]deca-2,4,9~trien-7,8-dlone Monooxime (33) vith o-

Phenylenedlamine. Oximinoketone 22. (0.5 g* 0.0029 mole) and o-phenylene- diam ine ( 0 .3 1 g, 0.0029 mole) vere refluxed in ethanol (10 ml) - acetic 1 0 4 acid (10 ml) f o r 1 hr. Qfce reaction mixture vas cooled and poured into vater; the product vas filtered and air dried (0.30 g, 46%). Recrystalli zation from methanol produced the pure quinoxaline derivative of bicyclo-

[4.2.2]deca-2,4,9-trien-7,8-dione (£4)> 194.5-195°J ir (KBr pellet):

1500 (m), 950 (s), 760 (s), and 730 cm "1 (s ); nmr: ' fi 7.85 (AaB2 , 4H, aromatic C-H), 6.1 (m, 6H, H at C-2, -3, -4, -5, -9, -10), and 4.35 (m, 2H,

H at C-l, - 6 ). Exact m aB s: calcd 232.1000; found 232.1004.

Anal. Calcd for CieHi 2N2: C, 82.73* H, 5.21; N, 12.06.

Found: C, 82.48; H, 5.19* N, 12.10.

Reaction of Bicyclo[4.2.2]deoa-2,4,9-trien-7-one (l) vith Sodium Methoxide and Methyl Formate. Ketone 1 (0.88 g, 0.006 mole) vas added to a suspension of freshly prepared sodium methoxide ( 1.30 g, 0.024 mole) in dry ether

(100 ml). After addition of methyl formate (1.43 g, 0.024 mole), the reaction mixture vas stirred for 22 hr. Cold hydrochloric acid (3N, 30 ml) vas added and the mixture extracted vith ether (2x). The combined ethereal vashes vere extracted vith vater ( 3x), saturated brine (lx), and filtered through Drierite. Concentration of the solution yielded a brovn oil (l.OO g> 95%) vhich completely solidified from pentane to a tan solid. Analyti cally pure 8-fornylbicyclo[4.2.2]deca-2,4,9-trien-7-one ( 38) vas prepared by elution through a silica gel column ( 25 % e th e r/ 75 % cyclohexane solvent) and subsequent crystallization from pentane at -78°, mp 58-57°; ir (KBr pellet): 1660 ( b ), 1580 (a ), and 1120 cm-1 (m); nmr: 6 8 .1 (a, 1H, ald e- hydic C-H), 5-9 (m> 7H, H at C-2, -3, -4, -5, - 8, -9, -10), and 3-5 (m, 2H,

H at C-l, - 6). Exact mass: calcd 174.0681; found 174.0683;

Anal. Calcd for CnHio02: C, 74.84; H, 5*79.

Found:. C, 75*55; H, 5*75* 1 0 5

Reaction of 8-Formylbicyclofli.2.23deca-2*U*9-trien-7-one ( 38) v i t h Hydrazine. Formy3ketone 38 (O.52 g, 0.003 mole) was dissolved in

ethanol (l ml). Anhydrous hydrazine (0.13 g, 0.00U mole) in ethanol (3 ml) vas added (precipitation occurred immediately) and the stirred mixture was

refluxed 18 hr. The dark solution was cooled* poured into vater (50 ml)*

and extracted vith ether (5>0 • The combined organic layer was vashed with

saturated trine, filtered through Drierite* and concentrated. The dark oil

( 0 .3 2 g) was eluted through a silica gel column (ethyl acetate solvent) to

yield a difficultly crystalllzahle oil (O.UU g* 86$). Analytically pure

3*4-diazatricyclo[5»^*2.0a,6]trideca-2,5*8*10*12-penfcaene (39) was prepared ty two re crystallizations from henzene/cyclohexane* mp 106-107°; ir (KBr):

3250 cm"1 (s); nmr:- 8 9*25 (hr s, 1H* N-H, shift is concentration depen

dent, disappears upon addition of Da0), 7.15 (b, 1H, H at C-5), 5 .9 (m, 6h*

H at C-8* -9* -10* -H , -12* -13), and k.O (m, 2H* H a t C -l, - 7 ) . Exact mass: calcd 170.08^; found 170.081*7.

Anal. Calcd for CxiHioNa: C* 77.62; H, 5.92.

Found; C, 77*35* H, 6 .O9 ,

Reaction of 8-Formylbicyclo [k.2.2]deca-2,4,9-trien-7-one ( 58 ) with Tosyl

Azlde and Triethylamine. Fornylketone (l.O g, 0.0575 mole) was dissolved

in methylene chloride (30 ml) and triethylamine (1.22 g* 0.12 mole) and tosyl azide (l.l g* 0.0575 mole) vere added at 25°. The mixture was stirred for

4 hr. Potassium hydroxide (5 g) in water (60 ml) was added and the mixture vas stirred an additional 15 min. After separation of the layers and subse quent extraction of the aqueous layer with methylene chloride (2x), the

combined organic phases vere vashed with vater (2x) and dried over anhydrous 1 0 6 potassium carbonate. Concentration yielded a dark brown oil (0.92 g) which

contained the product and tosyl azlde as indicated by micro tic analysis

on silica gel 0 with 1:1 ether-hexane solvent. Separation on a silica gel

column ( 1:3 ether-cyclohexane) yielded 7-diazobicyclo[4.2. 2 ]d e c a -2 ,4 ,9 - t r i e n- 8- one ( 37) as a bright yellow liquid which crystallized at - 20° and remained solid upon rowarmlng (0.52 g, 55^)* mass spectrum (P-N 2 ) m/e = 144;

ir (neat): 21J0 ( s ) , I 65 O ( s ) , 1350 ( s ) , and 1220 cm-i (s); nmr: 6 5-9

(m, 6H, H a t C-2, -3, -4, -5, -9, -10), and 3*65 (m, 2H, H at C-l, - 6).

Photolysis of 7-Dlazobicyclo[4.2.2]deca-2,4,9-trien-8-one (37) in Water-

Dloxane. Diazoketone £7, (°*75 S» 0.0044 mole) was dissolved in £>-dloxane

(50 ml) and water (25 ml) and the solution was degassed with a stream of argon f o r 0 .5 hr. The solution was then irradiated with a 450 watt medium pressure Hanovia lamp in all quartz equipment for 6 hr. Upon completion of the experiment, ^7 was absent as evidenced by the lack of evolution of

nitrogen upon addition of a drop of concentrated hydrochloric acid to an aliquot of the reaction mixture. The solution was concentrated (20 ml) under reduced pressure, and then the residue was triturated with aqueous potassium carbonate and extracted with ether. The aqueous layer was acidi fied with hydrochloric acid (3N) and extracted vith ether (5x). The com bined ethereal layer vas washed with vater and saturated brine and then filtered through Drierite. Concentration of the organic phase yielded a single product (0.43 Bt 6l %) a8 evidenced by micro tic analysis (1:1 ether- petroleum ether solvent).

The product vas filtered through a short column of silica gel and re crystallized from ether-petroleum ether at - 78° to provide pure bicyclo- 107 <43 [4.2.11nona-2>4,7-trlen-jajm-9-carboxyllc acid (40), mp 173-174.5° (lit mp 173-174°), as vhite crystals; ir (KBr); 3150 (br, s), 1730 (a), and

1680 cm"1 (s); nmr; 6 11.2 (s, 2H, -C00H, shift is concentration depen dent), 6.1 (m, 4H, H at C-2, -3, -4, -5), 5.25 (d, 2H, H at C-7, - 8), and

3.3 («, 3H, H at C-l, -6, -9). Exact mass; calcd 162.0681; found 162. 0683, 43 The material vas identical in all respects to that reported by Sanders.

Reaction of Blcyclo[4.2,l]nona-2,4,7-trlen-syn-9-carboxyllc Acid (40) vith Diazomethane. Crude acid 1*0 (O .35 g, 0.0022 mole) vas dissolved in e th e r (50 ml) and treated vith dlazomethane ( 0 .3 M; 30 ml, excess) at 25 ° and stirred for 0 .5 hr. Formic acid vas added to destroy excess diazomethane. The ether layer vas extracted vith aqueous sodium bicarbonate, saturated brine, and filtered through Drierite. Concentration under re duced pressure yielded a yellow oil (0.4l g) which vas ca 99# pure by glc analysis (column A). D istillation afforded pure methyl bicyclo[4.2.1]nona-

2, 4 , 7-trlen-syn- 9-carboxylate (4l) as a vhite solid, bp 66. 5 ° (0.05 ®®)* mp 27-29°i (0.37 St 93#); ir (neat): 1720 (s), 1220 (s), and 1205 cnr 1 (s ); nmr; 6 5.9 (m, 4h, H at C-2, -3, -4, -5), 5-15 (d, 2H, H at C-7, - 8), 3 .5

(s, methyl C-H) superimposed on 3.3 (n, H at C-l, - 6, -9, total 6h ).

Exact mass: calcd 176.0837; found 176.0840.

Anal. Calcd for CuRi^Os; C, 74.98j H, 6. 86.

Found; C, 75.19; H, 6.90.

Reaction of 7-Diazobicyclo[4.2.2]deca-2,4,9-trien-8-one (%[) vith Acetic

Acid. Diazoketone £7, (0.88 g, 0.0051 mole) vas dissolved in acetic acid

(12 ml) and stirred at 25° for 4 hr. The reaction flask vas fitted vith a 1 0 8 Vigreux column ana distilling head and the reaction mixture vas distilled

(25° pot temperature, 6 mm) to remove excess acetic acid. The column was removed and the residue vas distilled to produce pure exo-2-acetoxyblcyclo-

[5.2.1Jdeca-3»5>8-trien-10-one (44) as a clear liquid (0.87 g, 84?6),

102- 103° (0.1 mm); ir (neat); 1760 (s), 1740 (s), 1370 (m), and 1230 cm"1

(s); nmr: 5 5 .9 (m, 6h, H at C-3, -4, -5, -6, -8, -9), 5.00 (t, 1H, H at

C -2), 3*24 (m, 1H, H a t C -7), 3-05 (dd, 1H, H a t C -l), and 2 .1 1 ( s , 3H, methyl C-H); uv: 200, 225, and 285 nm (e = 6080, 4000, and 600).

Exact mass; calcd 204.0786; found 204.0788.

Anal. Calcd for C 12H12O3 : C, 7 0 .6 0 ; H, 5*88.

Found: C, 70.80; H, 5 . 83.

Attenrpts to purify 44^ by preparative glc (column A, inj «= 250 , column

= 225) produced endo-6-(cis-2,-acetoxyvinyl)-cis-'bicycloC3. 3 .0]octa-3,7- dien-2-one (57) as the major product (93^) as a pale yellow solid, mp 69-

71°- Rearrangement of 4-5 vas temperature dependent; only 70J6 of the re arranged product was formed at 150 ° (injector = 200°) while 85 ^ conversion was observed at 180° (injector ■ 230°); ir (KBr): 1760 (s), 1695 (a),

1220 (s), and 1040 cm"1 (s); nmr: 6 7.5 (dd, 1H, H at C-4), 7.14 (dd, 1H,

H at C-2'), 6.08 (dd, 1H, H at C-3), 5.80 (m, 1H, H at C-7 or -8), 5.50

(m, 3H, H at C-7 or -8), 4.69 (dd, 1H, H at C-l), 4.14 (br t, 1H, H at C-6),

3 .8 0 (m, 1H, H a t C -5), 3.46 (m, 1H, H a t C - l) , and 2 .1 ( s , 3H, m ethyl C-H); uv: X ^ 6r 208 nm (emnv. = 31,500). Exact mass: calcd 204,0786; found

204.0788.

Anal. Calcd for C 12H12O3 : C, 7 0 .6 0 ; H, 5*88.

Found: C, 70 .6 8 ; H, 5 .9 0 . 1 0 9

Hydrolysis of endo- 6-(c is-2♦ -acetoxrvlnyl)-cis-blcycloT3.3.01octa-3.7-

dien-2-one (^J_)« Acetoxyketone %J_ (53,1 mg, 0,00026 mole) was dissolved,

in chloroform-d ( 0 ,5 ml) and treated with water (3 drops) containing

trifluoroacetic anhydride (l drop) for 6 days with continuous swirling)

the reaction was monitored by nmr. The aqueous layer vas removed) the or

ganic layer was dried over anhydrous potassium carbonate and concentrated

- under reduced pressure to produce a clear oil ( 39.0 mg) which contained

two major components by glc analysis (column A), The product endo- 6- ( l* -

oxoethyl)-cls-blcyclor3.3.01octa-3,7-dlen-2-one (60, relative retention

tim e = 1. 0, relative area $ = 60, overall yield = 75$) and starting material

(relative retention time «= 1 . 7, r e la tiv e a re a $ = 15 ) were collected by

preparative glc,

Ketoaldehyde 60 was purified with large I o b s in material to yield

8 mg of pure compoundj ir (neat): 1715 (s ) and 1700 cm- 1 (s); nmr: 6

9.80 (s, 1H, H at C-2), 7.32 (dd, 1H, H at C-4), 6.02 (dd, IE, H at C-3),

5.6 (m, 2H, H a t C-7, - 8), 3.65 and 3.45 (two m, 3H, H at C-l, - 5 , - 6),

and 2.6 (br d, 2H, H at C-2’). Exact mass: calcd 162.0681) found

162.0683.

Catalytic Hydrogenation of exo-2-Acetoxybicyclo[5*2.1 ]deca- 3, 5 , 8- tr ie n -

10-one (44). Acetoxyketone 44 (l.06 g, O.OO 52 mole) was dissolved in

absolute ethanol (100 m l), 10?> palladium on carbon ( 0 .1 g) was added and

the mixture was placed in a Parr apparatus (P - 50 lb) for 6 hr. The reac

tion mixture was filtered through Celite to remove the catalyst and the ■ solvent removed under reduced pressure. The residue was taken up in ether,

vashed with saturated brine, filtered through Drierite and concentrated 1 1 0 under reduced pressure to yield a clear oil (1.07 g). The material vas eluted through a silica gel column, first vith ether/cyclohexane (l: 3 ) t o remove inpurities and then with ether to yield a clear oil (0,80 g, 73%) which crystallized on standing.

Analytically pure exo-2-acetoxybicyclof5.2.11decan-10-one ( 50 ) vas collected by preparative glc (column A) as a vhite solid, mp ir

(KBr): 1730 (s), 1370 (m), 12^0 (s), and 1230 cm-1 (s); nmr: & 2.05 (s, acetoxy m ethyl C-H) superimposed on 1.85 (m, a lip h a tic C-H). Exact mass: calcd 210. 1256 | found 210. 1260.

Anal. Calcd for CipHiqO^: C, 68.55; H, 8. 63#

Found: C, 68.28; H, 8 .5 7 .

Reaction of exo-2-Acetoxyblcyclo[5.2.l]decan-10-one ( 50 ) vith Sodium Hydroxide in Methanol-Water. Acetoxyketone 50 (0.70 g, O.OO 53 mole) was dissolved in hot methanol (10 ml) and sodium hydroxide (l pellet, ca O.OOh mole) dissolved in vater (l ml) vas added. The reaction vas stirred at 25° for

1 day. The mixture vas poured into vater (50 ml) and the aqueous layer extracted with ether (3x). The combined ether extract vas washed with saturated brine, filtered through Drierite, and concentrated under reduced pressure to yield an oil ( 0 .5 2 g) which vas greater than 99% pure by glc analysis (column A). The material vas eluted through a silica gel column

(gradient elution: 20% ether-cyclohexane, 50 % ether-cyclohexane, ether) o to produce a clear oil which vas recrystallized from pentane at -78 to provide exo-2-hydroxybicyclo[5.2.1]decan-10-one ( 51 ), a pure vhite crystal line product, rap 47-^8.5° (0.27 g, 50%); ir (KBr): 3U5 O (s) and 173° cm"x

(s). Exact mass: calcd 168.1150; found 168.1153* I l l

Oxidation of exo-2-Hydroxybicyclor5.2. l*)de can-10-one ( 51 ) with Chromic

Acid. Hydroxyketone jjl (0.20 g, 0.0012 mole) vas dissolved in acetone

(10 m l). Chromium trio x id e d isso lv ed in 25$ s u lfu ric a c id (2 .6 M, 1 ml,

0.0026 mole) was added dropvise and the mixture was stirred rapidly for

0 .5 hr. Methanol (0.15 ml) vas added to quench excess oxidant, and the mixture was diluted with 2 volumes of water and extracted with ether (tac).

The aqueous layer was acidified and extracted with ether; the aqueous layer was then made alkaline and re-extracted with ether. The combined ethereal extract was washed with vater, aqueous sodium bicarbonate, and saturated brine. Filtration through Drierite and concentration under re duced pressure provided a yellow liquid (0.21 g, 100$) which contained one component based on glc analysis (column A). The material was purified by preparative glc to yield pure bicyclo[5.2.l]decan-2,10-dione ( 52 ) as a clear liquid; ir (neat); 173° (s) a^d 1700 cm"1 (s). Exact mass; calcd

166. 099^; found l 66. 0996> The product was dissimilar in a ll respects to b ic y c lo [4 . 3 .l]decan-7,10-dione (5?) prepared from 1-morpholinocycloheptene 44 and acroyl chloride as previously described.

Anal. Calcd fo r CioHrtQg: C, 72.26; H, 8.1*9.

Found; C, 72.13; H, 8. 53 .

Reaction of 7 -Diazob icyclo[U. 2.2]deca-2, U, 9-trien-8 - one ( 37) with Hydrogen

Chloride. Diasoketone (0.69 g» 0.00U mole) was dissolved in dry ether

(10 ml) and hydrogen chloride was bubbled through the solution for 15 min.

The solution vas allowed to stand an additional 13 min; the reaction mix ture vas then diluted with ether (1*0 ml) and extracted with vater (2x), aqueous sodium bicarbonate (lx), and saturated brine. The organic layer was 1 1 2

filtered through Drierite and concentrated under reduced pressure to yield

exo-2-chloroblqyclor5. 2. H d e ca -3 . 5 .8- tr le n - 10-one (54) as a yellow liquid

« (0.68 g, 94$) • The compound was extremely labile# a ll attempts to purify

the material vere unsuccessful# ir (neat): 1740 cm *1 (s)# nmr: 6 5*9 (n»

7H, H at C-2, -3, -If, -5, - 6, - 8, -9 ) and 3 .2 (m, 2H, H a t C -l, - ? ) . Exact

mass: calcd 180.0342# found I 8O.O3H.

Attempts to d istill or preparatively glc chloroketone led to quan

titative rearrangement to endo-6-(2'-£is-chlorovinyl)-ciB-blcyclo[3.3-0]“

o cta- 3, 7-d ie n - 2-one (g 8) as a yellow liquid# ir (neat): 1700 cm*1 (s)# nmr:

6 7.5 (dd, 1H, H at C-4), 5.9 (m, 5H, H at C-3, -7, - 8, -1', -2'), 2.75

(m, 2H, H at-C -5 , - 6), and 2.5 (m, 1H, H at C-l)# uv. 208 nm (cmnv

31.3 x 103). Exact mass: calcd 180.0342# found 180.0342.

A nal. Calcd fo r CioHaClO; C, 66.49# H, 5*02.

Found: C, 66.14# H, 4.87.

Catalytic Hydrogenation of exo-2-Chlorobicyclo[5.2. l]deca-3,5,8-trlen-10-one

(54). Crude chloroketone ^4_ (0.48 g, 0.0027 mole) was dissolved in absolute ethanol containing 10$ palladium on carbon ( 0.06 g) and the mixture was placed in a Parr apparatus (hydrogen pressure = 50 lb) for 6 hr. The reac tion mixture was filtered through Celite and the residue was vashed vith ether (2x). The filtrate was concentrated under reduced pressure. The # residue vas taken up in ether and vashed vith saturated brine, filtered through Drierite and concentrated again to yield a yellow oil (0.40 g).

Micro tic analysis (l:9 ethyl acetate;petroleum ether) of the oil shoved two components, values.of, 0 .8 and 0 . 5 . The crude product was eluted through a silica gel column (5$ ethyl *■ acetate-petroleum ether solvent); the first material off the column weighed

0 .2 8 g and was found to he a mixture of a saturated and unsaturated ketone by glc (column A), ir, and maBS spectral measurement (m/e = 150, 152 ).

The mixture of ketones was dissolved in absolute ethanol (35 ml) con ta in in g 10$ palladium on carbon ( 0 .0 5 g) and rehydrogenated in an atmos pheric pressure hydrogenator. Hydrogen uptake ceased after 2 hr and the product mixture worked up as before to yield an oil ( 0 .2 5 g, 6l$ ) which was greater than 98$ pure by glc analysis. Pure bicyclo[5.2.l]decan-lO- one (££) was collected by preparative glc and possessed spectral properties 4 3 identical to those reported for the previously reported compound, mass 4 3 spectrum m/e = 152 ; ir (neat): 1730 cm*1 (lit 1731 cm"x); nmr: 6 2 .1

(s) superimposed on 1.9 (m). Exact mass: calcd 152.1201; found 152.1204.

The ir differed from that reported for bieyclo[4.3.1]decan-10-one (Sadtler

*e8389).

Reaction of Bicyclo[5,2.lldecan-10-one (5J?) with 2,4-dinitrophenylhydrazine.

Ketone ^ (O.O 76 g, 0.0005 mole) was treated with 2,4-dinitrophenylhydra- z in e ( 0 .2 g) dissolved in concentrated sulfuric acid (2 ml), water (3 m l), and methanol (5 ml) to yield a crude derivative (precipitation occurred after 30 min), 0.l4 g (82$). Pure bicyclo[5.2.1Jdecan-10-one dlnitro- phenylhydrazone ( 56 ) was obtained after recrystallization from ethanol as bright orange plates, mp 175 - 176° (lit mp 176-177.5 ° )t *Ve ** 332. 4 6 Admixture with an authentic sample of the derivative showed no melt ing point depression; both sanples possess identical ir spectral proper ties; ir (KBr); 33OO (w), 3100 (w), l6l0 (s), and 1330 cm- 1 (s). Exact mass: calcd 332.1484; found 332.1488. 2 1 k

Reaction of exo-2-Chloroblcyclo[5.2.lldeca-3.5»8-trien-10-one (ph) vith Sil- ver Acetate. Chloroketone (0.2U g, 0.0013 mole) was dissolved in acetic a c id (5 ®l) containing silver acetate ( 0 . 1+3 g , 0.0026 mole) in a flask wrapped vith aluminum fo il to exclude light. The reaction mixture was stirred at 25 ° f o r 3 days, diluted with ether (UO ml) and filtered to remove a light tan precipitate. The precipitate was washed with two addi tional portions of ether (10 ml). The combined filtrate was washed vith water (*+x), saturated sodium bicarbonate (2x), and saturated brine. F il tration through Drier it e and concentration of the filtrate yielded a yellow liquid (0.19 g). Evaporative distillation (0.075 nm) provided a yellow liq u id (O.16,g) containing 10$ starting chloroketone by glc analysis.

The major component of the mixture (80$) by glc was exo- 2-acetoxybicyclo-

[ 5 . 2.l] d e c a - 3, 5 , 8- t r ie n - 10-one (M+, overall yield « 1+7$) identical in a ll respects to the previously prepared acetoxyketone Ml. Acetoxyketone

M+ prepared in this manner also rearranged to endo-6-( 018- 2 * -acetoxyvinyl)- cis-bicyclo[3.3.0]octa-3,7-dien-2-one (57) upon preparative glc as pre viously described.

Attempted Wolff-Kishner Reduction of Bicyclo[h.2.2]deca-2,1+.9-trien-7- one (l). Ketone 1 (0.25 g > 0.0017 mole), potassium hydroxide (O .75 g ), and hydrazine hydrate ( 1 .5 ml) were refluxed in ethylene glycol ( 1+ ml)

(bath temper at \ire = 200°) for 2 hr. The stirred mixture was cooled an additional 0.5 hr, poured into water (100 ml) and extracted with pentane

(1+ x 25 ml). The conibined pentane layer was filtered through Brierite and concentrated to yield an off-white solid ( 0.13 g) which contained two highly volatile materials ( 5$) of short retention time and a material ( 95 $) of long retention time by glc analysis (column A). 115

Pure 2,3-diazatricyclo[6.3.1.0 4 * 11]dodeca-2,5,9-triene (64^ overall y ie ld = b'J'fc) was collected as a white solid hy preparative glc, mp 170- 172° .

A fresh SE-30 glc column was necessary for consistent glc results; ir

(mull): 1650 (v), 1560 (w), and 9^0 cm-l (m); nmr; 6 6 .0 ( t , 2H, H a t

C-9, -1 0 ), 5*3. (m, 3H, H a t C-4, - 5 , - 6), 4.6 (t, 1H, H at C-l), 2.6 (m,

3H, H a t C-7, - 8, -11), 2.1 (t, 2H, H at C-ll, -12), and 1.8 (septuplet,

IK, H at C-12); uv: X ^ lohexane 200 and 333 nm (emax = 3,700 and 330).

Exact mass: calcd 160.1000; found 160.1003*

Anal. Calcd for CioHi 2N2: C, 74.97; H, T .55* N, 17-48.

Found: C, 74.79; H, 7.72; N, 17.57.

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) with Hydrazine.

Ketone 1 (0.22g, 0.0015 mole) and hydrazine hydrate (10 ml) were warmed for 2 hr at 75°. The mixture was extracted with chloroform (3x); the chloroform layers were filtered through potassium carbonate and concentra ted under reduced pressure to yield bicyclo[4.2.2]deca-2,4,9-trien-7-one hydrazone ( 65 ) as a yellow oil (0.23 St 96?>); ir (neat); 333° (m), 3200

(m), and 165 O cm"1 (m); nmr: 6 5 .8 (m, 6h, H at C-2, -3, -4, -5, -9, -10),

4 .7 5 (broad s , 2H, N-H, d isap p ears w ith DfeO), 3 .5 (m, 3H, H a t C-6) , 2 .9

(m, 1H, H a t C -l), and 2 .4 (m, 2H, H a t C- 8 ). Exact mass: calcd 160.1000; found 160. 1003.

Reaction of Bicyclo[4.2.2]deca-2,4,9 -trien-7-one Hydrazone ( 65 ) with Tosyl

Chloride. Hydrazone 6£ (0 .1 1 g, O.OOO69 mole) was added to tosyl chloride

(0.14 g, 0.00073 mole) in dry pyridine (l ml) and the mixture was stirred at 25° for 9 hr* The reaction mixture was quenched with water (25 ml) and extracted with methylene chloride (3x). The combined organic layers were 116

vashed vith water (ix), aqueous sodium 'bicarbonate (lx), and saturated

brine, filtered through Drierite and concentrated to yield a brown oil

(0.18 g, 86$). The oil was crystallized from ethanol after charcoal de

color izat ion to yield material identical to the previously prepared tosyl-

hydrazone 12 In ir and nmr spectral properties, mp 154-157°.

A ttested Wolff-Kishner Reduction of Bicydo[4.2.2]deca-2,4,9-trien-7-one

Hydrazone ( 65.). Potassium t-butoxide (O .15 g, 0.0014 mole) was dissolved

. in dry dimethylsulfoxide (1.5 ml). Hydrazone 6£ (0.15 g, 0,0009 mole) dis

solved in dry dimethylsulfoxide ( 3 .0 ml) was added dropwise over 5 min.

After stirring for 2 hr, the reaction mixture was quenched with pentane (JO

ml) and water (30 ml). The aqueous layer was then washed with ether (30

ml) and the combined organic layer was washed with saturated brine, filtered

through D rierite and concentrated to yield a tan solid (0.08 g) which was

85 $ pyrazoline 64 by glc analysis (overall yield 0 48$). Two other vola

tile products (combined yield = 8$) were not identified.

Attempted Wolff-Kishner Reduction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one

Semlcarbazone (£). Semicarbazone (1.54 g, O.OO 76 mole) and potassium

hydroxide ( 5 .5 g) were refluxed (bath temperature = 190°) in ethylene glycol

(20 ml) for 2.5 hr. The mixture was cooled, poured into water ( 15 O m l),

and extracted with pentane (5 x 30 ml) and ether (2 x 30 ml). The combined

organic layer was washed with saturated brine, filtered through Drierite,

and concentrated under reduced pressure to yield a tan solid ( 0.68 g) which

was 94$ 2 , 5 -diazatricyclo[ 6. 3 . 1. 04 , 11]dodeca- 2, 5 , 9-triene (64) by glc analy

sis (column A) (overall yield = 54$). Two volatile minor components (com

bined yield 3$) were not identified. U 7

Attempted Wolff-Kishner Reduction of Bicyclo[4. 2.2]deca-2,4,9-trien-7-one

(l) using Benzoylhydrazlde as a Source of Hydrazine In Situ. Ketone 1

(0.25 B> 0.0017 mole), potassium hydroxide ( 0.75 g) and benzoyl hydrazide

(0.34 g, 0.0025 mole) were dissolved in ethylene glycol and refluxed for 5 hr (bath temperature = 200°). The mixture was cooled to room temperature, quenched with water (50 ml) and extracted with pentane (4x). The conibined pentane layer was filtered through Drierite and concentrated to yield a pale yellow solid (0.15 g). Glc analysis of the product shoved the major 4 ix component to be 2,3“diazatricyclo[6.3.1.0 * ]dodeca- 2, 5 ,9-triene (64, rela tiv e a re a f a 90, overall yield = 5°^)* Three minor volatile products

(combined yield = 5$) were not identified.

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) with Methylhydrazine.

Ketone 1 (0,12 g, 0.0008 mole) was warmed to 75° with methylhydrazine (5 ml) for 18 hr. Water (20 ml) was added and the mixture extracted vith chloro form (3x). The organic layer was dried through potassium carbonate and concentrated under reduced pressure to give bicyclo[4. 2 . 2]deca-2, 4 ,9- tr ie n -

7-one methylhydrazone (J 2, 0 ,l4 g, 100#)j ir (neat): 3350 (m), 1620 (m), and 1100 cm"1 ( s ) j nmr: fi 5*75 (m, 6h, H at C-2, -3, -4, -5, -9, -10), 3*9

(m, 1H, N-H, disappears with D^o), 3*35 (quintet, 1H, H at C- 6), 2 .8 (d imposed on m, 4H, H at C-l, methyl C-H), and 2.4 (m, 2H, H at C- 8). Exact

0 mass: calcd 174.11571 found 174.1159.

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) with Methylhydrazine and Potassium Hydroxide in Ethylene Glycol. Ketone 1 (0,28 g, 0.0019 mole)

* « potassium hydroxide ( 0,75 g)'and methylhydrazine ( 1 .5 ml) were refluxed in ethylene glycol (4 ml) for 2.5 hr at a bath temperature of 200°. The reaction 1 1 8 mixture vas poured Into vater (60 ml) and extracted with pentane (4x). The combined pentane extract vas filtered through D rierite and concentrated under reduced pressure to yield a yellow oil (0.24 g, 749>) vhich vas homo geneous by glc analysis (column A).

Pure 3-methyl-2,3-diazatricyclo£6.3.1.0 4 , 113dodeca-l,5,9-triene ( 73) v as collected by preparative glc. A fresh SE-30 column vas necessary for con sistent glc results; Ir (neat): 1640 (v), 1610 ( v ) , 1600 (v ), and 1420 cm"x

(m); nmr: 6 6.00 (m, 2H, H at C-9, -10), 5.80 (m, 1H, H a t C -5), 5.56 (m,

W, H a t C -5), 3 .8 2 (m, 1H, H a t C -4), 3 .4 9 (m, 2H, H a t C- 8, -ll), 2.75

(s, 3H, methyl C-H), 2.48 (dd, 1H, H at C-12), 2.1 (mf 2H, H at C-7, -12), and 1.64 (dd, 1H, H at C-7). Exact mass: calcd 174.1157; found 174.1159*

Anal. Calcd for CiiHi 4 Na: C, 75.82j H, 8 .1 0 ; N, 17.08.

Calcd: C, 75 .68; H, 8 .0 1 ; N, 16.77.

Reaction of Bicyclo[4.2.23deca-2,4,9-trlen-7-one (l) vith Dimazine. Ketone

1 (0 .1 0 g, O.OOO63 mole) vas dissolved in dimazlne (3 ml) and refluxed for

36 hr. The mixture vas diluted vith vater (20 ml) and extracted with methylene chloride (3x). The organic layer vas dried over potassium car bonate and concentrated under reduced pressure to yield bicyclo[4.2.2]deca-

2,4,9-trien-7-one dimethylhydrazone ( 7 6) as a yellov oil ( 0 .0 9 g, 75^)l Ir

(neat):l6l0 cm-1 (m); nmr: 6 5.7 (m, 6h, H at C-2, -3, -4, -5, -9, -10),

3 .4 (m, W, H at C-6), 2.7 (m, 3H, H at C-l, -8), and 2.3 (d, 6h, methyl

C-H). Exact mass: calcd 188.1313; found 188.1315*

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) vith Dimazine and Potas sium Hydroxide in Ethylene Glycol. Ketone 1 (0.10 g, O.OOO 69 mole) and excess dimazine (l ml) vere refluxed in ethylene glycol (3 ml) for 1 hr. The mix- 1 1 9 ture was slowly cooled to room temperature ( 0 .5 hr) and poured into water

(50 ml) containing saturated brine solution (15 ml). The mixture was ex-

» tracted with pentane (4x). The combined extracts were filtered through

Drierite and concentrated under reduced pressure yielding bicyclo[4.2.2]- deca-2,4,9-trien-7-one dimethylhydrozone ( 76) as a yellow oil (0.12 g, 92%).

The product was identical in all respects to the dimethylhydrazone JjS made p rev io u sly .

Reaction of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) with Sodium Borohydride.

Ketone !L (l. 5 g, 0.0103 mole) vas dissolved in methanol (l? ml) and cooled to 0°. Sodium borohydride (0.15 g, 0.04 mole, 1.16 mole hydride) dissolved in w ater (3 ml) and aqueous sodium hydroxide (2N, 0.6 ml) was added a ll at once and the mixture vas stirred at 0° for 1.0 hr. The solvent was removed under reduced pressure. The residue was diluted with water and ether and the ether layer was washed with saturated brine and filtered through Drierite.

Concentration of the organic layer yielded a pale yellow oil (1.40 g, 92%).

Elution through a silica gel column (ether-cyclohexane solvent system) and crystallization from pentane at -78° produced pure bicyclo[4.2.2]deca-2,4,9- trlen-syn-7-ol (j j ) as white crystals, mp 35 -36°; preparative glc (column

A) yielded the analytical sample; ir (neat): 3330 (s).and 1070 cm-i (s); nmr: 6 5*8 (m, 6 h, H at C-2, -3, -4, -5, -9, -10), 3.9 (m, 1H, H at C-7),

# 2.4 (broad m, 4H, H at C-l, -6, -8), 1.9 (s superimposed on broad m at 2.4,

1H, hyd rox yllc 0-H, d isap p ears upon a d d itio n o f IfeO). Exact mass: calcd

148.0888; found 148.0890.

Anal. Calcd for CioHigO: C, 81.04; H, 8,l6.

Found: C, 81.28; H, 8.23. 1 2 0

Reaction of Bicyclo[4.2.2]deca-2, 4,9 -trlen-syn-7-ol (££) vith Acetic Formic

Anhydride. Alcohol 77 (0.48 g, 0,003 mole) was dissolved in excess acetic formic anhydride (l ml, ~ 0,01 mole) and warmed to 60° for 0.5 hr. The mixture was then stirred an additional 24 hr at 25 ° and vacuum d istilled

(pot temperature «= 55 - 60°) a t 33 mm to remove excess anhydride and acetic acid. The residue, a clear liquid (0.54 g, 100f>), vas > 98$ pure by glc analysis (column A) and by nmr. Analytically pure bicyclo[4.2.2]deca-2,4,9- trlen-syn-7-yl formate (J9) vas obtained by preparative glc; ir (neat):

1740 (s) and 1190 cm -1 ( s ) ; nmr: 6 7*7 (s , 1H, form ate C-H), 5.5 (m, 6h ,

H at C-2, -3, -4, -5, -9, -10), If . 8 (m, 1H, H a t C-7), 2.85 (broad m, 2H,

H at C-l, - 6) , and 2 .0 (m, 2H, H a t C- 8). Exact mass: calcd 176.08371 found 176.0840.

Anal. Calcd for Ciaflia02: C, 74.98; H, 6. 86.

Found: C, 75*19; H, 6.71.

Reaction of Bicyclor4.2.21deca-2.4.9-trlen-ayn»7-ol (7j) with Triphenyl phosphine Dibromlde in DimethyIformamlde. Triphenylphosphine dibromide

(0.003 mole) was prepared by adding bromine (0.48 g, 0.003 mole) to a solu tion of triphenylphosphine ( 0.79 8, 0.003 mole) in freshly dried dimethylfarmamide (10 ml) and stirring the mixture for 0 .5 h r a t 25 ° .

Alcohol 77 (0.40 g, 0.00275 mole) dissolved in dry dlmethylformamlde # (5 ml) was added to the above solution and the mixture vas stirred for 2 .0 h r. W ater (100 ml) was added and the resulting suspension vas extracted with ether (3x). The combined ethereal layers were washed vith saturated brine, filtered through Drierite, concentrated and eluted through a silica gel column with ether/cyclohexane (l:9)* Removal of the solvent under reduced pressure yielded a yellow liquid ( 0.25 g) which was analyzed by

glc analysis (column A). The material vas a five component mixture with

the major material accounting for 75-80$ of the product. Collection of the major product by preparative glc produced material identical in all

respects to bicyclo[l*. 2 . 2ld ec a-2, 1*, 9-trien-syn- 7- yl formate ( 79; 1*0-J* 5$ yield). Attempts to identify the minor products were unsuccessful.

Irradiation of Bicyclo[l*.2.2]deca-2,1*, 9-trien-7-one (l) in Acetone. Ketone

1 (0.50 g, O.OO3I* mole) was dissolved in dry reagent grade acetone (150 ml) and degassed with a stream of argon for 0 .5 hr. The solution was then

irradiated with a 1*50 V Hanovia medium pressure lamp through a Vycor f il t e r fo r 9 hr in all quartz apparatus fitted with a reflux condenser and a

stirrer. The solvent vas removed under reduced pressure. The residue

(0 .6 g) was loaded on a silica gel column (90 g), gradient eluted with 5 $ ethyl acetate-petroleum ether (500 ml) and 35 ?> ethyl acetate-petroleum e th e r ( l l) and collected in 12 ml c u ts .

Cuts 28-35 contained starting ketone 1 (0.05 g, 10$).

Cuts 38-1*1 contained a clear oil, Isomeric with the starting ketone, and homogeneous by glc (column A) (0.06 g, 12$). A pure sample of trl- c y c lo [ 5 . 3 . 0 . 02 , l o ]deca- 3>5 -d ie n - 8-one ( 8J0 was prepared by preparative glc* ir (neat): ' 17l*0 cm "1 ( s ) ; nmr: 6 5*9 (m, 1*H, olefinic C-H), 3-3

(br t, 1H), 2.5 (m, 1H), 2.0 (m, 2H),'and 1.5 (m, 2H, aliphatic C-H).

Exact mass: calcd 11*6.0732* found IU 6 .O73I*.

Cuts 1*3-50 contained tricyclo[3.3.2.0a, 8]deca-3,6-dien-9(l0)-one ( 8jS) as a clear oil ( 0 . 3I* g, 68$) which was homogeneous by glc analysis. Pure 5 1 8£ was obtained by preparative glc, mp 1*0- 1*1° ( l i t mp 38-37 )i 8^ was 1 2 2

identical in all respects to an authentic sample; ir (neat): 1665 cm"1

5 1 (s); ir (CCI4 ): 1685 cm*1 ( l i t 1685 cm"1); nmr; 6 5 .8 (m, 4h, H a t

C-5, -4, -6, -7) and 2.5 (m, 6h, H at C-l, -2, -5, -8, -10 (-9))* uv; ^heptane 2Q0f ^ ^ ^ ^ m e 7fkQQf 13Q# l03j ^ ^

6l). Exact mass; calcd 146.0732; found 146.0734.

Anal. Calcd for Ci o Hi q O: C, 82.16; H, 6.89*

Pound; C, 81.93) H, 7.19. 5 1 The nmr of 8)5. is temperature dependent as reported.

Irradiation of Bicyclo[4.2.2]deca-2,4,9-trien-7-one (l) in Ether. Bstone

1 (0.50 g, 0 . 0031J- mole) vas dissolved in anhydrous reagent ether (100 ml) and purged vith argon for 0 ,5 hr and irradiated vith a 450 W Hanovla medium pressure lamp for 9 hr vith Pyrex optics. Concentration under re duced pressure yielded a yellow oil (O. 5 O g, 100/6) yhich vas shown by g lc analysis (column A) to be a mixture of ketone 1 (relative retention time <3

1. 0, relative area $ = 25 ), tricyclo[ 5 . 3 . 0 . 02, l o ]deca- 3, 5 -d ie n - 8-one (84y relative retention time = 1. 1, relative area % = 27), and tricyclo-

[3 . 3 . 2 . 02 , 8]deca-3, 6-d ie n - 9 ( l 0 )-one ( 83, relative retention time = 1.4, relative area % = 48).

Irradiation of Bicyclo[4.2.23deca-2,4,9-trien-7-one (l) vith Michler's

Ketone as Sensitizer. Ketone 1 (0.25g, 0.0017 mole) and Michler's ketone

(0.50 g) vere dissolved in dry benzene (100 ml) and degassed vith a stream of argon for 0.5 hr. The solution vas then irradiated vith a 450 V Hanovla medium pressure lamp through Pyrex optics for 2 .5 hr. The solution vas filtered, concentrated, and rapidly eluted through a silica gel column 1 2 3

vith ether. The residue vas finally sublimed at 50-60° at 0.1 mm to yield

tr ic y c lo £3 . 3 . 2 . 0s , a ]d eca-3 , 6-d le n - 9 ( l 0 )-one ( 0£) as a white solid ( 0 .1 1 g,

Preparation of Barbaralone. Barbaralone vas prepared according to the 28 method of T. A. Antkowiak in 6h% yield from bicyclo[U. 2. l]nona-2,l+,7-

trlen-9-one by Michler's ketone sensitized irradiation, mp ^9-51°| nmr:

5 5.7 (conplex t, 2H, H at C-3, -7), ^.3 (con^lex t, IfH, H at C-2, -k, - 6,

- 8 ), and 2.7 (t, 2H, H at C-l, -5).

5 1 Reaction of Barbar alone vith Dlazomethane. Alcoholic ethereal diazo-

methane (125. 0.33 Ml O.OUl mole) as previously prepared vas added at

- 5 ° to barbaralone ( 0 . 8l g, 0 , 006l mole) dissolved In methanol (15 m l).

After 28.5 hr, solvent and excess dlazomethane were removed under reduced

pressure to yield a yellow oil ( 0 .9 1 g, 100^) consisting of 9-aldehydo-

tricyclo£3.3.1.02 ,e]nona-3,6-diene (relative retention time « 1 . 0, r e l a

t i v e a re a $ «= 5*0 and tricyclo[ 3 . 3 . 2 . 02, 8 3d eca-3, 6-d ie n - 9 ( l 0 )-one ( 8^

relative retention time = 1.8, relative area $ = h 6). The aldehyde and

k eto n e 85 were purified by preparative glc (column A); 9-aldehydotricyclo-

C3.3.1.02,e]nona-3,6-diene exhibits nmr absorptions at 6 9.5 (d, 1H,

aldehydic C-H), 5-7 (t, 2H, H at C-3, -7), 4.1 (m, hH, H at C-2, -4, -6,

- 8 ) , 2 .8 (m, 2H, H a t C -l, - 5 ), and 2.0 (m, 1H, H at C-9). Ketone 8£ is

Identical to the previously prepared ketone spectrally (glc, ir, and nmr).

2# 3 Reaction of Tricyclo[5.3» 2«0 3deca-3,6-dien-9-one (83)vith Tosylhydra-

zlde. Ketone 83 (0.20 g, 0.00135 mole), tosylhydrazide (0.25 Bt 0.00135 mole) and one drop of concentrated hydrochloric acid were dissolved In 1 2 4 absolute ethanol (6 ml) ana stared for 2 hr at 25° and 10 hr at -5°. The reaction mixture vas concentrated to ca 2 ml under reduced pressure,

stored at - 25 ° and the resulting precipitate collected hy filtration ( 0 .2 8 g, 68$). The vhite crystalline product is identical to bicyclo[4.2.2]- d eca-2, h, 9 - t r ie n - 7-one tosylhydrazone ( 12) previously prepared, mp 155 - o 1^7 • The residue after filtration also is exclusively tosylhydrazone 12 by nmr a n a ly s is .

Reaction of TricycloC3.3.2.0 2 ,e]deca-3,6-dien-9-one ( 83) w ith D ilu te T r i- fluoroacetlc Add. Ketone 85 (ca 25 mg) vas dissolved in chloroform-d

(0 .5 ml) and treated vith vater (3 drops) and trifluoroacetic anhydride (l drop) and swirled overnight at 25°* After the aqueous layer had been separated, the organic layer vas removed, dried over anhydrous potassium carbonate, and filtered. Nmr and glc analysis of the resultant solution revealed the exclusive presence of bicyclo|[4.2.2]deca-2,4,9-’fcrien-7“One (l).

Reaction of Tricyclo[3.3.2.0a,B]deca-3,6-dien-9-one ( 85 ) with Sodium Boro- hydrlde. Ketone 8^ (0.l6 g, 0.0011 mole) vas dissolved in methanol (5 m l) and cooled to 0°. Sodium borohydride (0.20 g, xs) vas dissolved in v a te r (2 ml) and sodium hydroxide ( 2N, 0.4 ml) and added to the ketone solution. The mixture vas stored at 0° for 15 hr. After the methanol had been removed from the mixture under reduced pressure, the residue vas taken up in ether (30 ml) and vater (30 ml) and the aqueous layer vas washed vith ether (3 x 3° ml). The cornbined organic layer vas washed vith saturated brine, filtered through D rierite and concentrated to yield a yellow oil (0.l4 g, 88$) which contained only one component by glc analysis

(column A). 2 2 3

Pure trlcyclot5.3.2.0 2, 83deca-3,6-dien-9-ol (§8) was collected by preparative glc; ir (neat): 3550 ( s ) , 16^5 (v ), and 1620 cm"1 (v)> nmr:

6 5-8 (m, 2H, H a t C-3, - 7 ) , 5 .1 (b r t , 2H, H a t C-lf, -6 ), 3 .8 (m, 1H,

H a t C -9), 2.3 (b r m, 6 h, H at C-l, -2, -5, -8, -10), ana 2.0 (a, Ifl, hydroxylic 0-H, shift is concentration dependent, disappears upon addi tio n o f Ds0)t uv: X ^ f”01 198 and 225 nm (e^ «= 12,100 and 3,670).

Exact mass: calcd lU8,0888j found 1^8.0891.

Anal. Calcd for CioHxaO; C, 8l.0^j H, 8.l£.

Pound: C, 8 l.l^ j H, 8.39. 5 1 Infrared data previously reported, matched the observed spectrum of 88. Nmr of alcohol 88 vas temperature dependent. APPENDIX I

IR AND NMR SPECTRA 4000.3000 2000 1500 tool-—..1—

,40

1601 c*'1

FIGURE I

40003000 , 2000 1500

'CD 140

' 4 ' 4 ' 6 ' W L U i FIGURE 2

40003000 2000 1500 1Q00 9p0 6Q0 IQQ 1 i i OtO

i40

FIGURE 3 TRANSMTIANC&CX) TRANSMTTANCEftJ TRANSMTTTANCEK) i S 8 § ° . 8. s . 8, j IUE If FIGURE

JL lll.ll ,1 .1--71---T— M I .I T I'.r .(— T--- T" E° '"SiSva'Sosa* - 1500 1000 9Q0 8Q0

60 QAc 140

FIGURE T

4000 3000 2000 1500 tOO'......

60 K-CH ,40

FIGURE 8

4 0 0 030 00 2000

>60 i40

20 l£01 w*

FIGURE 9 40003000 2000 IQ00 9Q0 8Q0 KX)

;60

}40

*"* lfiO l c a " 1

FIGURE 10

40003000 , 1 0 0 0 900 !00 !■*“““■ i. “ .i

FIGURE 11

2000 1500 <10

'60 i40

FIGURE 12 4C 003000 2000 1000 9Q0 8Q0

8 0

GO i40

20 ■*» 1601 car1

FIGURE 13

4 0 0 0 3 0 0 0 2 0 00 1500 looo 9po epo 100- ...... OO

60 AeO

4 0 0 0 3 0 0 0 2000 1500 100 OtO

, e 6 \ r *60

140 QAe 20

FIGURE 15 132 4 0 0 0 3 0 0 0 2Q00 700 1001 .i— ~ 0-0

■60'

FIGURE 1 6

2000 1500 IQOO 9Q0 0 0

i40

FIGURE 17

4 0 0 0 3 0 0 0 2000 1500 IQOO 9Q0 6Q0 OO

0 0 ^ 60

140

FIGURE 18 2000 1500 IQOO 9Q0 epo 00

60 i40

=10

FIGURE 19

Q O Q 6000 0 3 0 0 0 , 2000 IQOO 9Q0 6Q040 V} In.w.1 . . *. i ■ 00

FIGURE 2 0

2000 IQOO 9Q0 8Q0 0 0

FIGURE 21 4 0 0 0 3 0 0 0 2000 1500 IQOO 9Q0 8Q0 roo OO

,40

20 lfiOl cm’ 1

FIGURE 22

CM* IQOO 9Q0 8Q04000 3Q00 2000 1500 IQOO 9Q0 8Q04000 100 010

,40 *.4z

20 V 1601

FIGURE 23

4000 3QOO 2QOO 1500 7(?0 _ (00 “* . - 1 rO.0

20 :10

FIGURE 2k 1000 s - g - g - i 8 6 P (ft) PPM ■00 FIGURE 25 h «oo 2 0 1000 • CM IM

8 6 PPM (fl) k 2 0

FIGURE 26 1000I >00 • O S ■soI

W 'n l'r

. . u . . . . . f ...... i . . I i 1 . . PPM ( 6)

FIGURE 27 3 T"1"' ' i | i ' i ' . i i J i i i i « i . . j- ' i J I ' I i l i i i * t e n

1111111 i 11111 ■ 1111 ■ I ...... it.,.,. 6 PPM (6 )

FIGURE 28 •00 *W

PPM (fi)

FIGURE 29 epm (a)

• FIGURE 30 21

A* ii

A J V _

i _ L *dh* ...... ■. i-LI » « ■ *. I . . a a t 1 ‘ * *. ‘ '.*.' ‘ 1'. *r*? e E?M (6 )

FIGURE 51 7.0 t.0 w

' FIGURE 32 FIGURE 33 FIGURE & tom too to*

PPM (6 )

FIGURE 35 IOOQ too too IM W

f | iirf

PPM (8 )

FIGURE 36 aw UD

PPM (6 )

FIGURE 37

5 1000 100 tftO

»0

...... ;

i p k ( i y

FIGURE 3 8 idoo * I '''1 I T 1 ‘ 1.1 i i i i i ( i.i i i i i ' » f j' I •0I 0 » . t e n no ilo •0l

CHsCH u 0 6o V ’tt , » 9.80 %

0 ♦ « * ♦1 1 >■■»■■■■>■» 1 ...... I...... t. . . I" •8 6 PPM (6 )

FIGUEE 39 >000

MO WO • cos MO

8 6 PPM (6 ) 1+ 2 0

FIGURE ho FIGURE FIGURE 1+1

L|—1—J—! 3*0 W>M(r) 6.0

*r i

FIGURE k Z

I •DO •00 t»0

•0

8 6 PPM (6 ) h 2 0

FIGURE k ? H O ' MO *•0

8 *6 k 2 0

FIGURE 44 1000 s - g - H .OH FIGURE k5 too vn vn H