INFORMATION TO USERS Thil material was produced from a microfilm copy of the original documant. While the moat advanced technological meant to photograph and reproduce this documant have been used, the quality is heavily dependant upon the quality of the original submitted. The following explanation o f techniques is provided to help you understand markings or patterns which m ay appear on this reproduction. 1. The sign or "target" for pages apparently lacking from the document photographed is "Misting Page(s)". If it was possible to obtain the misting page(s) or section, th a y era spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pagae to insure you complete continuity. 2. Whan an image on th e film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus causa a blurred image. You will find a good image of the pnga in the adjacent frame. 3. Whan a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It ie customary to begin photoing at the upper left hand comer of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again —beginning below the first row end continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Department, giving the catalog number, tide, author and specific pages you w ish reproduced. 5. PLEASE NOTE: Some pages may have indistinct print. Filmed as received. Xarox University Microfilms 300 North ZMbRMd Ann Arbor, Michigan 4S100
Transcript
INFORMATION TO USERS
Thil material was produced fro m a microfilm copy of the original documant. While the moat advanced technological meant to photograph and reproduce this documant have been used, the quality is heavily dependant upon the quality of the original submitted.
The following explanation o f techniques is provided to help you understand markings or patterns which m ay appear on this reproduction.
1. The sign or "target" for pages apparently lacking from the document photographed is "Misting Page(s)". If it was possible to obtain the misting page(s) or section, th a y era spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pagae to insure you complete continuity.
2. Whan an image on th e film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus causa a blurred image. You will find a good image of the pnga in the adjacent frame.
3. Whan a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It ie customary to begin photoing at the upper left hand comer of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the first row end continuing on until complete.
4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered a t additional charge by writing the Order Department, giving the catalog number, tide, author and specific pages you w ish reproduced.
5. PLEASE NOTE: Som e pages may have indistinct print. Filmed as received.
Xarox University Microfilms300 North ZMbRMdAnn Arbor, Michigan 4S100
PRESS, J e f f 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 S ta te U n iv e rs ity , P h .D ., 1973 C hem istry, o rg an ic
University Microfilms. A XEROX C o m p an y # 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 P a r t i a l F u lfillm en t o f th e Requirements fo r th e Degree Doctor o f Philosophy in th e Graduate
School o f The Ohio S ta te U niversity
By
J e f fe ry Bruce P re ss , B.S.
# * * * *
The Ohio S ta te U niversity
1973
Reading Conmittee; Approved hy
Dr. Harold Shecbter
Dr. Paul Gassman
Dr. Robert O uelle tteAdviser
Department o f Chemistry
DEDICATION
To my p a re n ts
11
ACKNOWLEDGMENT
The au tho r i s g r a te f u l to Dr. Harold S hech ter fo r suggestion o f
t h i s problem, f o r h i s ev e r-p re sen t enthusiasm and Im aginative guidance
and f o r h is a id in p re p a rin g t h i s m anuscript. D r. S h e c h te r 's w it,
im agination , and knowledge provided s tim u la tio n and encouragement during
th e course o f study .
The au th o r i s indeb ted t o M essrs. Gary B lrriberg and J . Michael
Geckle and Dr. P a u l Gassman f o r en lig h ten in g d isc u ss io n s concerning exper
im ental r e s u l t s . He i s f u r th e r indebted to Mr. Geckle f o r bo th measure
ment and I n te r p r e ta t io n o f nmr d a ta which was e s s e n t ia l f o r completion
o f t h i s work and to Miss C arol Rose fo r h e r s k i l l and p a tie n c e in ty p in g
and i l l u s t r a t i n g th e f i n a l m anuscript. The au th o r a ls o w ishes to acknow
ledge in te r e s t in g d isc u ss io n s o f bo th chem ical and non-chem ical na tu re
w ith M essrs. B lrnberg , Geckle, Roger Drewes, and Gordon Gruetzmacher a t
lo c a l pubs in Columbus.
The au tho r must exp ress deep a p p re c ia tio n t o F h i l l lp u s Aureolus
Theophrastus Bombastus von Hohenhelm who p ro v id es th e e te r n a l l ig h t to
a lchem ists everywhere and l a s t l y to h is w ife , Debbie, whose many lonesome
n ig h ts allow ed com pletion of much of th iB work.
i l l
VITA
May 2h, 1 9 k 7 .................................................. Born - R ochester, New York
1 9 ^ 9 ................................................................... B.S. - BuckneU U n iv e rs ity ,Lewishurg, Pennsy lvan ia
1 9 6 9 -1 9 7 3 ........................................................ Teaching A s s is ta n t , Department o fChemistry, The Ohio S ta te Univers i t y , Colunibus, Ohio
1973 . ............................................................... Research A sso c ia te , Department o fChemistry, The Ohio S ta te Univers i ty , Columbus, Ohio
'The Chemistry o f B ic y c lo [^ .2 .1 1 n o n a -2 ,^ ,7 -tr ie n -9 -o n e , B icyclo(.U .2.1]- n o n a -2 ,4 ,7 - tr ie n -9 -y l In te rm ed ia te s and T heir D e r iv a t iv e s ," T. A, Antkowiak, D. C. Sanders, G. B. T r im its is , J . B. P re s s , and H. S hech ter, J . Amer. Chem. S o c ., 9hj 3366 (1972).
“F a c ile Synthesis o f B icy c lo [4 .2 .2 1 d e ca -2 ,4 ,7 > 9 -T e trae n es ," J . B. P ress and H. S hech ter, T e t. L e t te r s , 2677 (1972).
. G en era l P rocedures and T e c h n iq u e s ............................................................... 60
P re p a ra t io n o f B iq y c lo [4 .2 .1 ]n o n a -2 , l i ,7 - t r ie n - 9 - o n e ....................... 8 l
R e a c tio n o f B ie y c lo [U .2 .1 ]n o n a -2 ,lf ,7 - tr ie n -9 -o n e w ithD ia zo m e th an e ......................................................................................................... 6
R e a c tio n o f B ic y c lo [^ .2 .2 ]d e c a -2 ,l t- ,9 - tr ie n -7 -o n e ( l ) w ithSem icarhazlde H y d ro c h lo r id e ....................................................................... 82
P r e p a ra t iv e I s o la t io n o f B ic y c lo [lj- .2 .2 3 d ec a -2 ,U ,9 -tr ien -7 -o n e ( l ) .............................................. 83
R e a c tio n o f B ic y c lo £ h .2 .2 ]d e c a -2 ,lf ,9 - tr ie n -7 -o n e ( l ) w ith2 ,l* -D in itro p h e n y lh y d ra z in e ............................................7*......................... 8^
R e a c tio n o f B ic y d o [J |.2 .2 ]d e c a -2 ,i f ,9 ," t r ie n -7 -o n e ( l ) w ithHydroxylam ine H y d ro c h lo r id e ........................................................................ 8*f
C a ta ly t i c H ydrogenation o f B icy c lo [i|. 2 .2 ] d e c a - 2 ,^ ,9 - t r ie n -7 -o n e ( l ) ................................................................................................................ 83
V
Page
R eaction of B icyc lo [4 .2 .2 ]decan -7 -one (4 ) w ith 2 , lf-D in itro - p h e n y lh y d ra z in e ........................................... 7 . .......................... 65
R eaction of B icyclo[l+ .2 .2]decan-7-one (U) w ith Sem lcarbazideH ydrochloride ................................................................................................... 66
C a ta ly t ic Hydrogenation o f B icyclo[U .2 . l]n o n a -2 ,U ,7 - tr ie n -9 - o n e .................................. ............................................ -.................................• . 86
R eaction o f B icyclo[U .2.1]nonan-9-one (6 ) w ith Diazomethane . . . 87
B ase-C atalyzed Mono- and D id e u te ra tlo n of B lcyclo[U .2.2Jdeoa- 2 ,U ,9 - t r i e n - 7-one ( l ) ......................................................... 87
R eaction o f B icy d o [U .2 .2 ]d eca -2 ,J+ ,9 -tr ien -7 -o n e ( l ) w ith * Potassium t-B u to x ld e and Deuterium O x id e ............. 7 . ...................... 88
R eaction o f B ic y c lo [U .2 .2 ]d e c a -2 ,4 ,9 - tr le n -7 “One ( l ) w ith Potassium t-B u to x id e and Water in Dim ethylform am l'de........ 88
R eaction o f B ic y c lo [^ .2 .2 ]d e e a -2 ,4 ,9 - tr ie n -7 -o n e ( l ) w ith T o B y lh y d raz ld e .....................................................................7 . ...................... 89
R eaction o f B icy c lo [^ .2 .2 ]d eca-2 ,4 ,9 * * trien -7 -o n e ( l ) w ith B enzenesulfonylhydrazide ............................................... 7 . ...................... 89
R eaction o f B ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e Tosylhydra-zone (12) w ith M e th y lll th iu m ................................................................... 90
R eac tion of B ic y d o [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e ( l ) w ithIsopropeny l A c e t a t e .......................................................... 7 . ...................... 91
R eac tio n o f B icy c lo [U .2 .2 ]d eca-2 ,l* ,9 -trien -7 -o n e ( l ) w ithPotassium t-B u to x id e and A cety l C h loride in G lym e...................... 91
R eaction of 7 -A c e to x y b icy c lo [if .2 .2 ]d ec a -2 ,^ ,7 j9 -te tra en e (15) w ith 3N H ydrochloric A c id ......................................................................... 92
R eaction o f B icy d o [ 4 .2 .2 ]deca-2 , U, 9 - tr ie n -7 -o n e ( l ) w ithP y r r o l i d in e ............................................................................7 . ...................... 92
R eaction o f 7 -P y rro lid in o b icy c lo [l;.2 .2 ]d ec a -2 ,U ,7 > 9 -te trae n e(1 6 ) w ith 3N H ydrochloric A c id ............................................................. 95
R eaction o f B ic y c lo [4 .2 .2 ]d e c a -2 ,U ,9 -tr ie n -7 -o n e ( l ) w ith Potassium t-B u to x ld e and M ethyl F lu o ro su lfo n a te Tn Hexa- m ethylphosphoram lde.................................................................... 95
v i
Page
R eaction o f p -T etra lone w ith Potassium t-B utoxlde and Dimethyl S u lfa te in Dimethylformamide” ............................................... 9k
R eaction o f B icy c lo [U .2 .2 ]d eca-2 ,l|- ,9 -trien -7 -o n e ( l ) w ith Potassium t-B u tox lde and Methyl F lu o ro su lfo n a te in Glyme . . . . 96
R eaction of 7-M ethoxybicyclo[lf.2 .2]deca-2 ,1^7>9“te tra e n e(17) w ith H ydrochloric A c i d ............................... •................................... 98
R eaction o f B lc y c lo [^ .2 .2 ]d e c a -2 ,U ,9 -tr ie n -7 -o n e ( l ) , w ith Potassium t-B u to x id e and T r im e th y ls ily l Chloride"*in Glyme . . . 99
Thermal Rearrangement o f 7-M ethoxybicyclo[^.2 .2 ] d e c a - 2 , 7>9- te t r a e n e ( r f ) ................................................................................................... 99
P re p a ra tio n o f 2 -M ethoxynaph thalene .......................................................... 100
R eaction o f B icy c lo [U .2 .2 ]d eca -2 ,U ,9 -tr len -7 -o n e ( l ) w ithLead T e t r a a c e t a t e ..............................................................7 . ....................... 101
A cid-C atalyzed R eaction of a n t i - 8 -Acetoxyhicyclo[>+.2 .2 ] -deca-2,U #9 - tr ie n -7 -o n e (26) w ith M e th an o l......................................... 101
R eaction o f syn- 8-M e th o x y b ic y c lo .2 .2 ]d eca -2 ,U ,9 -tr ien -7 -o n e(28) w ith 2 ,4 -D in itro p h e n y lh y d ra z in e .................................................... 102
Attem pted A cid-C atalyzed H ydro lysis o f a n t i - 8-A cetoxyblcyclo- [4 .2 .2 ]d ec a -2 ,ll- ,9 " trien -7 -o n e ( 26 ) in Dimethylformamide- W a te r ...................................................................................................................... 102
R eaction of B icy c lo [U .2 .2 ]d ec a -2 ,lf ,9 -tr ien -7 -o n e ( l ) w ithIso an y l N i t r i t e and P o tassium t - B u to x ld e 7 . ...................... 103
R eaction o f B icy d o [li- .2 .2 ]d e ca -2 ,lf ,9 “'tr ien -7 j8 -d io n e Mono-oxlme (%£) w ith o -F h en y len ed iam in e ........................................................ 103
R eaction o f B ic y c lo [ if .2 .2 ]d e c a -2 ,^ ,9 - tr ie n -7 -o n e ( l ) w ithSodium Methoxide and M ethyl F o rm a te ....................... 7 . ....................... 10^
R eaction o f 8 -F a rn y Ib ic y c lo [l* ,2 .2 ]d ec a -2 ,^ ,9 -tr ie n -7 -o n e(38) w ith H y d ra z in e ......................................................................................... 103
R eaction o f 8 -F o rm y lb ic y c lo [^ .2 ,2 ]d e c a -2 ,^ ,9 -tr ie n -7 -o n e(38) w ith T osyl Azide and T r ie th y la m in e ............................................. 103
P h o to ly s is o f 7 -D iazd b icy c lo [lf .2 .2 ]d eca-2 ,lj- ,9 -trien -8 -o n e(37) in W ater-Dioxane ........................................................................... 106
v i i
R eac tio n o f B lcycloC ^.2 . 1 1 n o n a -2 ,U ^ 7 -tr len -sy n -9 "ca rb o jty lic A d d (40) w ith D ia zo m eth an e .................................................
R eac tio n o f 7 -D iazo b icy c lo [4 . 2 . 2 ]d e c a -2 ,k , 9-trien -8 -on< ! (37) w ith A ce tic A c i d ..........................................................................
H y d ro ly sis o f endo- 6 - ( e l s - 2 ' - a c e to x y v in y l)- c l s -b ie y e lo - C 5»5»°]oc ta -3 j7 -d ien -2 -one ........................................
C a ta ly t i c H ydrogenation o f e x o -2 -A ce to x y b ic y c lo [5 .2 .l]* ‘ deca-3 i 5 » 8 -tr ie n -1 0 -o n e (W ) ...............................................
Page
107
107
109
109
R e ac tio n o f exo-2 -A c e to x y b lcy c lo [5 .2 . l]d ecan -1 0 -o n e (gO) w ithSodium Hydroxide in M e th a n o l-V a te r ..................................... 110
O x id a tio n o f exo-2-R ydroxybic y c lo f5 .2 . lld ecan -1 0 -o n e ( g l ) w ith Chromic A c i d ..........................................................................I ................. H I
R e ac tio n o f 7 -D ia z o b ic y c lo [4 .2 .2 3 d e c a -2 ,4 ,9 - tr ie n -8 -o n « (37 ) w ith Hydrogen C h l o r id e .................................................
C a ta ly t ic H ydrogenation o f e x o -2 -C h lo ro b ic y c lo [5 . 2 . l ]d e c a -3 ,5 ,8 - t r ie n - lO -o n e (j>4) ..................................... j ................. 112
113
111
R e ac tio n o f B ic y c lo [5 .2 .1 ]d e c a n -1 0 -o n e (5jj) w ith 2 ,U -d in itro - p h e n y lh y d ra z in e ............................................................................
R eac tio n o f exo-2 -C h lo ro b ic y c lo [5 .2 . 1 1 d eca -3 i5 .8 -tr ie n -lO -o n e (j§4) w ith S i lv e r A c e t a t e ........................................................
A ttem pted W olff-K ishner R ed u c tio n o f B ic y c lo [4 .2 .2 ]deca-2 ,4 ,9 - tr ie n -7 -o n e ( l ) ..............................................................
R e ac tio n o f B ic y c lo [4 .2 ,2 3 d e c a -2 ,4 #9 - t r le n -7 -o n e ( l ) w ith H y d ra z in e ........................................................................T . .
R e ac tio n o f B ic y c lo [4 ,2 .2 3 d e c a -2 ,4 ,9 - tr ie n -7 -o n e Hydra^one ( 6g_) w ith T osyl C h l o r id e ........................................................
A ttem pted W olff •K ishner R ed u c tio n o f B icy c lo [4 . 2 .2]decu-2 ,4 ,9 - tr ie n ~ 7 -o n e Hydrazone (6 5 ) ......................................
A ttem pted W olff-K ishner R e d u c tio n o f B ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 -trien -7**one Sem icarbazone (3 ) ...............................
A ttem pted W olff-K ishner R ed u ctio n o f B icycloCli. 2 .2 ]deca- 2 ,l+ ,9 - tr ie n -7 -o n e ( l ) u s in g B enzoy lhydraz ide as a Source o f H ydrazine In S i tu .................................................................
v i i i
114
114
115
115
116
116
117
Page
R eaction o f B lc y c lo [k .2 .2 ]d e c a -2 ,k ,9 - tr ie n -7 -o n e (:l) v i t h M eth y lh y d raz in e .............................................................................................. 117
R eaction o f B ic y c lo [k .2 .2 ]d e c a -2 ,k ,9 - tr ie n -7 -o n e ( l ) w ith M ethylhydrazine and Potassium Hydroxide in E thy lene G lycol . . 117
R eaction o f B ic y c lo [k .2 .2 ]d e c a -2 ,k ,9 - tr le n -7 -o n e ( l ) v i t h D im az in e ........................ 7. ....................... 116
R eaction o f B ic y c lo [k .2 .2 ]d e c a -2 ,k ,9 - tr ie n -7 -o n e ( l ) w ith Bimazine and Potassium Hydroxide in E thy lene G ly c o l .................. 116
R eaction o f B icy d o [^ .2 .2 ]d ec a -2 ,U / 9 - tr ie n -7 -o n e ( l ) w ith Sodium B o ro h y d rld e ............................................................ 77 ...................... 119
Reaction o f B icy c lo C ^ .2 .2 ]d e ca -2 ,lf ,9 -tr ie n -s jrn -7 -o l (77) w ith A cetic Formic A n h y d rid e ................................................................... 120
R eaction o f B icyclo [k . 2 . 2]deca-2, k , 9 - t r l e n -ayn- 7 - o l (77) v i t h Triphenylphosphine Dihromide in DimethylformamicTe 120
I r r a d ia t io n of B ic y d o [k .2 .2 ]d e c a -2 ,k ,9 - tr ie n -7 -o n e ( l ) in A c e to n e ................................................................................... 7. ................. 121
I r r a d ia t io n of B ic y c lo [k .2 .2 ]d e c a -2 ,k ,9 - tr ie n -7 -o n e ( l ) in E t h e r ....................................................................................... 7. ................. 122
I r r a d ia t io n o f B icy c lo C k ,2 .2 ]d e c a -2 ,k ,9 -tr ie n -7 -o n e ( l ) w ith M ic h le r 's Ketone as S e n s i t i z e r .............................7. ................. 122
P re p a ra tio n of B a rh a ra lo n e ............................................................................ 12?
R eaction o f B arh ard o n e w ith D iazom ethane........................................... 12?
R eaction o f T r ic y d o [ ? .? .2 . 0a ,6 ]deca-?#6-d ie n -9 -one (8?)w ith T o sy lh y d ra z id e ...................................................................................... 12?
R eaction o f T ricyclo [5 .?»2 .O a , 0]d ec a -? ,6 -d ien -9 -o n e (8? ) v i th D ilu te T r if lu o ro a c e t ic A c i d .......................................................... 12k
R eaction o f T r ic y d o [? .? -2 .0 a , 8]d ec a -? ,6 -d ien -9 -o n e (83 ) v i th Sodium B o ro h y d rld e .............................................................................. 12k
APPENDIX I - IR AND NMR SPECTRA............................................................................ 126
lx
LIST OF TABLES
Table Page
I P roduct D is t r ib u t io n from R eaction o f B icy c lo [U .2 .2 ]-d e c a -2 ,^ ,9 - tr le n -7 -o n e ( l ) v i th Potassium t-B u tox ide and Methyl F luoroB ulfonate in P o la r Solvents .7 ................................... 32
I I Ntnr Data Observed fo r 7 -S u b s titu te d BicycloCU ,2.2]deca-2,1*,7>9-Tetraenes l j^ IJ5, 16, and 2 1 ..................................... 36
I I I Nmr D ata R eported fo r S u b s titu te d B icy c lo [^ .2 .2 ]d eca -2 ,1* ,7> 9 -T etraenes........................................................................................ 37
IV Double I r r a d ia t io n o f endo- 6 - ( c l s - 2 t - Acet oxyvinyl) - c i s -b ic y c lo [3 -3 »0 ]o c ta -3#7 -d ie n -2-one (J57) .......................................... 56
V Eu(Fod)a Induced Chemical S h if t D ata fo r Compound 6k 6 l
VI Eu(Fod)3 Induced Chemical S h if t Data fo r Compound 7 3 ,............ 67
V II Product D is tr ib u tio n from R eaction of B icyclo [k . 2 .2 ]deca- 2 , k , 9 - tr ie n -7 -o n e ( l ) v i th Potassium t-B utox ide andMethyl F lu a ro su li’onaibe in Hexam ethylphosphoramide.................. 93
V III P roduct D is t r ib u t io n from R eaction o f B icy c lo [k .2 .2 ]d eca - 2 ,l+ ,9 -tr ien -7 -o n e ( l ) v i th Potassium t-B utox ide andMethyl F lu o ro siilfo n a te in G lym e 7 ........................................... 97
x
" I lea rn ed t h i s a t l e a s t , by ny experim ent; t h a t i f one advances c o n fid e n tly in th e d ire c tio n o f h is dreams, and endeavors t o l iv e th e l i f e which he has imagined, he w i l l meet w ith a success unexpected in common ho u rs . In p ro p o r tio n as he s im p lif ie s h is l i f e , th e la v s of th e u n iv e rse w i l l appeal l e s s comp le x . . . I f you have b u i l t c a s t le s in th e a i r , your work need no t be l o s t ; t h a t i s where th ey should be . Now p u t th e foun d atio n s under them . n
Henry David Thoreau from Walden
STATEMENT OF THE PROBLEM
B icycloflf. 2 .1 ]n o n a -2 ,^ ,7 " tr ie n -9 -o n e is p o te n t ia l ly u se fu l f o r p re
p a rin g r in g expanded b ic y c l ic system s.
The p re s e n t re se a rc h invo lves sy n th e s is and study of b icy c lo [l4-.2 . 2 ] -
deca-2 , ^ , 9 - t r i e n - 7-one ( l ) as d e riv ed by r in g expansion of b ic y c lo [^ .2 . 1 ] -
n o n a -2 ,U ,7 -trien -9 -o n e v i th diazomethane. Ketone 1 i s to be in v e s tig a te d
f o r p rep a rin g b ic y d o [ l f .2 . 21deca-2 ,Jf,7>9 - te t r a e n e (3Jf) and 7- s u b s t i tu te d
b ic y c lo [ lf .2 .2 ]d e c a -2 ,lf ,7 * 9 -te tra e n e s . Photochem ical re a c tio n s o f ketone
iL a re a ls o o f i n te r e s t f o r sy n th e s is of novel b l - and t r i c y c l i c ke tones.
F u n c tio n a liz a tio n o f ketone !L a t C-8 may allow p re p a ra tio n o f b ic y d o -
[U .2 .2 ]d eca -2 ,4 ,9 -tr ien -T > 8 -d io n e (56) and i t s d e r iv a tiv e s . The p ro p e r t ie s
o f b icy c lo [l+ .2 .2 ]d eca-2 ,U ,9 “t r i e n - 7 - y l carbonium ion , carbene, carbanion
and r a d ic a l as w e ll as 8 -k e to b i c y c lo p . 2 . 2 ]deca-2 , 4 ,9 - t r len -7- y l carbene
and carbonium ion a re t o be in v e s tig a te d .
Expansion o f th e [4 .2 .2 3 b ic y c lic system may prov ide a ro u te t o
sy n th e s is o f b icy c lo [lf .5 .2 ]u n d e c a -2 ,4 ,8 ,1 0 -te tra e n e -7 -o n e . Study o f th e
g en e ra tio n and p ro p e r t ie s o f th e b i c y c l o ^ .3 .2 ']undeca-2 ,U ,8, 10- te t r a e n -
7 - y l carbene, carbonium ion and r a d ic a l i s proposed in attem pts t o study
p o s s ib le b lc y c lo a ro m a tic ity and s t a b i l i t y o f such sp e c ie s .
HISTORICAL
Hydrocarbons on th e (CH)io energy su rfa ce a re o f in te n se in te r e s t
because of t h e i r f a c i le photochem ical and th e rm al In te rc o n v e rs io n s . These
Isom eriza tion re a c t io n s p rov ide extrem ely s tro n g support fo r th e Woodward-x
Hoffmann s e le c tio n r u le s . S ince N enitzecsu re p o r te d th e f i r s t hydrocarbon
( l ) H. B. Woodward and R. Hoffmann, f<The C onservation of O rb ita l Symmetry,” Academic PresB , New York, N. Y. (1970).
2ly in g on th is energy su rfa ce in I 960, numerous p u b lic a tio n s concerning th e
p re p a ra tio n , iso m eriza tio n , and chem istry o f v a rio u s (CK)io compounds have3
appeared.
(2 ) M. Avram, E. Sliam , and C. D. N enitzecsu, A nn., 636, 18^ (i9 6 0 ).
(3 ) For review s of work in t h i s area see: (a ) T. L. Burkoth and E. E.van Tamelen, Chapter 3 o f "Noribenzenoid A ro m atics ,” Vol. 1 , J . P .Snyder, E d ., Academic P re s s , New York, N. Y. (1969)l and (b) L. T.S co tt and M. Jo n es, J r . , Chem. Rev., 72, l 8l (1972).
S c o tt and Jones p repared and c h a rac te rize d th e (CH)io hydrocarbon,
b ic y c lo lU .2 . 21d eca-2,U ,7 , 9- te t r a e n e , as th e major p roduct (37 .87) o f th e r
mal decom position of th e sodium s a l t o f 9 * fo rm y lb icy d o [6 .1 .0 3 n o n a -2 ,4 ,6 -
t r l e n e tosy lhydrazone. O ther p roducts in c lu d e e l s - and tran s -9 ,1 0 -d ih y d ro -
naphthalenes ( 11 .67 and 207, r e s p e c t iv e ly ) , c y c lo o c ta te tra e n e (12 . 77 )#
2
3 , U -dihydronaphthalene ( 13 . yf>), c is - l-p h e n y lb u ta d ie n e (k.6%), and naphtha-4 5
le n e ( l$ ) (E quation l ) . The decom position p rocess 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. Jo n es, J r . , S. I>. Reich, and L. T. S c o tt, i b i d . , £2, 3118 (19T0).
CKH a®0
-NTs90-120
\ +
(1)
00* 00* 0*00invo lve carbene g e n e ra tio n follow ed by cleavage to a d i r a d ic a l which in
tu r n recombines t o form p ro d u cts (Equation 2 ) .
B icy c lo [U .2 .2 3 d ec a -2 ,lf ,7 ,9 -te trae n e has a ls o "been p repared "by photo
chem ical rearrangem ent o f c l s - 9 . 10-d lhydronaphthalene fo llow ed hy therm al6 , 7 , 8
opening, I r r a d ia t io n o f e l s - o r t r a n s -9> 10-dlhydronaphthalene as w ell
(6 ) W. von E. Doering and J . W. R osen thal, I b i d . , 88, 2078 (1986).
(7) W. von E. Doering and J . W. R osen thal, T e t. L e t te r s , 3^9 (1967)*
(8 ) M. Jones, J r .# J . Amer. Chem. S o c ., 8ft, 1*236 (1967) .
as b ic y c lo [6 . 2 , 0 ]deca-2 , ^ , 6, 9 - te t r a e n e produces th e same r a t i o o f p roducts,2 IO S T
namely th e rm ally u n s ta b le te trac y c lo [l* .l* .0 ,0 1 .0 * 3deca”3 , 8-d lene (65%),
t r a n s - 9 , 10-d lhydronaph thalene ( 20%), c l s - 9 . 10-d lhydronaphthalene (8%), and9
b u llv a le n e (7%) (E quation 3)* The te t r a c y c l i c hydrocarbon opens v ia
(9 ) S . Masamune, R. T. S e idner, H. Zenda, M. W iesel, N. Nakatsuka, and G. Bigam, I b i d . , 90, 5286 (1968).
a th e rm ally allowed *w2 p ro cess t o produce b ic y c lo [^ .2 . 2 ]deca-2,U ,7 , 9-
te traen e# opening t o d s “9»10-d lhydronaphthalene in a h+1* re a c tio n I s no t
therm ally allowed and Is no t observed (E quation U),
C a ta ly tic Iso m eriza tio n o f b u llv a len e a ls o produces th e b ic y c lic [ lf .2 .2 ] -
te t r a e n e . Thus m ercuric o r z in c h a lid e s produce b i c y e lo C ^ .S ^ d e c a - S , ! ^ ^ "/ 10 te tra e n e (987") along w ith c l s - 9 , 10-d ihydronaphthalene and naphthalene.
(10) H. P . L o ff le r and G. S chroder, Angew. Chera. I n t . E d ., Jj 736 (1968) .
S im ila r rearrangem ent (60Jb y ie ld of th e d e s ire d te t r a e n e ) a ls o occurs upon11
use of b is (b e n z o n itr i lo )p a lla d iu m ch lo rid e . S u b s titu te d b u llv a len e s g iv exo
th e corresponding te tr a e n e s (Equation 5)* F lu o ro b u llv a len e rea rran g es
( l l ) E. Vedejs, J . Amer. Chem. S op ., 90, U751 (1968)
6
(5 )
R b Hf -CH3, -CQ2CH3
t o two t e t r a e n e s , one w ith f l u o r in e a t t h e 7 - p o s i t io n and th e o th e r w ith
. th e s u b s t i tu e n t a t th e 1- p o s i t io n .
Many and 7 > 8 -d is u b s ti tu te d b ic y d o t4 .2 .2 ] d e c a - 2 ,4 ,7 ,9 - te t r a e n e s
(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, J r . , and J . J . B loom fie ld , T e t . L e t te r s , 1121 (1969) .
(14) J . Altman, E. Babad, M. B. R ubin, and D. GinBburg, i b i d . , 1125 (1969).
(15) J . Altman, E. Babad, D. G insburg , and M. B. R ubin, I s r . J . Chem.,7 , 435 (1969).
(16 ) W. von P h il ip s b o rn , J . A ltm an, E. Babad, J . J . B loom field , D. G in B -b u rg , and M. B. Rubin, H elv . Chim. A c ta , 53? 725 (1976).
have been p rep a red by pho tochem ical rearrangem en t o f a p p ro p r ia te ly d isu b -l a - i e
s t i t u t e d c1b- 9 ,10-d ihydronaph thalenea (E quation 6 ) . P rofound changes
in th e product a re caused by s l ig h t su b s ti tu e n t m o d ifica tio n s; isom eriza
t io n v ia th e rm a lly allow ed in te r n a l forw ard and re v e rse D ie ls-A lder re a c
t io n s accounts f o r th e s e r e s u l t s (E quation 7 ) . Adequate exp lana tions fo r
th e s e s u b s ti tu e n t e f f e c t s have not y e t been advanced.
I I I I I I
Ri* Ra
-C0aCH3-CO-X-CO-
-CHaOCHa— —CHgOCO—
(X - 0- , -NH-, -NCH3- )
Product Form (isom er ♦)
II I I
I I II , I I , I I I m ixture
Some 7 ,8 -d ls u b s ti tu b e d b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,7 ,9 - te tra e n e s a re formed
in modest y ie ld s b y r e a c t io n o f d is u b s t i tu te d ace ty len es v i th tr ic a rb o n y l-17
c y c lo o c ta te tra e n e iro n (E quation 8 ) . Most ace ty len es tr im e r iz e under th e
r e a c t io n c o n d itio n s .
(IT ) U. K ruerke, Angew. Chem. I n t . E d ., 6, 79 (1967).
8
Pe(CO)3
+
6in
RI
(8)
R o phenyl, -CO2CH3, -Si(CHa)3
Photochem ical rearrangem ents of 9>10-d isubB titu ted b ic y c lo [6 . 2 .0 ]deca-
2 , ^ , 6 , 9 - te tr a e n e s a ls o g ive b icyclop+ . 2 . 2 ]d eca-2, k, 7, 9- t e t r a e n y l d e r iv a tiv e s ,9
B esides th e p a re n t system d escribed e a r l i e r , 9 -ch lo ro -lO -flu o ro b icy c lo -le
[6 .2 .0 ]d e c a -2 ,4 ,6 ,9 - te tra e n e (E quation 9) has been rea rran g ed v i th l i g h t .
( 18) H. R o tte le , P . H iko lo ff, J . F. M. Oth, and 0. Schroder, Chem. B e r . ,102, 5367 (1969).
F
Cl
(9 )
F n i
18A p o s s ib le r e a c t io n mechanism Invo lves pho to ch em ica lly a llow ed d i s r o t a -
« *t o r y r i n g opening to an a l l c is -c y c lo d e c a p e n ta e n e and th e rm a lly a llow ed
c o n ro ta to ry r in g c lo su re t o th e a p p ro p r ia te ly s u b s t i tu te d e i s - 9 , 10-d ih y d ro -
n ap h th a len e which th e n r e a c t s f u r t h e r a s p re v io u s ly d is c u s se d (E quation 1 0 ) .
CX d is con
C l
(10)
B icy c lo [4 .2 .2]deca-2 ,4 ,7> 9-tetraene and i t s d e riv a tiv e s iBOmerize
therm ally and photochemically. 7 -D eu terio [4 .2 ,2 ]deca-2 ,4 ,7> 9-te traene as
p rep a red from d e u te ra te d 9 - fo rn y lb ic y c lo [6 .1 .0 ] a e c a - 2 ,4 ,6 - t r ie n e undergoes19 12,20
d eu te riu m scram bling ; s im ila r o b se rv a tio n s have been made on th e
(19) M. Jo n es , J r . , and B. F a i r l e s s , T e t . L e t te r s , 4881 ( 1968) .
(20) R. T. B eidner, N. H akatsuka, and S. Masamune, Can. J . Chem., 48, 187 (1970).
7 ,8 -d id e u te r io d e r iv a t iv e (E quation l l ) . The Isom eric d i s t r i b u t i o n o f
10
deuterium i s s t a t i s t i c a l ) 66^ of th e deuterium i s on th e monoene b ridge
v h ile 33/6 1b on th e 3~ emd ^ -p o s itio n s . T his iso m eriza tio n i s s t r i c t l y
analogous t o th e p rev io u s ly d escribed fo r b icyclo [U . 2 . 2"1deca-2, 7>9 - t e t r a -
eny l systems v ia in te r n a l 4+2 cy c lo ad d itlo n and r in g opening (Equation ? ) .
Thermal rearrangem ents o f b ic y c lo l4 .2 .2 n d e c a -2 ,4 ,7 * 9 -te tra e n e s a lso
lead t o s u b s ti tu te d c l s -9»10-dihydronaphthalenes. Thus, c i s -9»10-dihydro-
naphthalene ( 20#) and naphthalene (80#) a re produced from th e p a re n t7
te tr a e n e (E quation 12). S im ila r ly , deuterium i s Incorpora ted on C-2, 3>
6 , and 7 ( 1*2 D) and 0 9 and 10 (0 .6 D) upon s ta r t in g v i th 7>8-d id e u te r io -20
b ic y c lo [4 .2 .2 ]deca-2 ,4 ,7 * 9**tetraene. Likewise th e 7>8 -d ipheny l d e r iv a tiv e17
therm olyzes m ainly t o 2 , 3 -d iphenylnaphthalene (E quation 13). A reasonab le
A(12)
5 4
in te rp r e ta t io n o f th e s e conversions t o naphthalenes involves in tram o lecu la r
D ie ls-A lder r e a c t io n s follow ed by d isallow ed 4+4 r in g openings t o produce
dihydronaph thalenes. Subsequent lo s s o f hydrogen lead s t o th e f u l ly a ro
m atic p roducts (E quation lh ) .
B icy c lo [lj-.2 .2 ]deca-2 ,l* ,7 j9 "te traenes may a ls o be isom erized photo-5
chem ically . I r r a d ia t io n o f th e p a re n t hydrocarbon produces b u llv a len e '
p o ss ib ly v ia a d i-n-m ethane rearrangem ent2 (E quation 15). S u b s titu te d
(21) H. E. Zimmerman and A. C. P r a t t , J . Amer. Chem. S o c ., 92, 6267 (1970) and re fe re n c e s con ta ined th e re in .
b u llv a le n e s have been p repared s im ila r ly . Thus I r r a d ia t io n o f 7>8-d ipheny l-IV
b icyclo[U . 2 . 2]deca-2 , U, 7 ,9“te t r a e n e y ie ld s d ip h en y lb u llv a len e . Chloro-xa
f lu o ro b u llv a le n e has been p repared analogously .t
B icyclo [l* .2 .2 ]deca-2 ,l* ,7> 9 -te traenes a re e le c tro n - r ic h and e x h ib it
marked r e a c t iv i ty w ith e le c t r o p h i l ic re a g e n ts . R eac tion o f th e p a ren t hydro-
(1*0
.1 2
-V
(15)
carbon v i th su p erac id le a d s t o p re p a ra tio n of th e b ic y c lo [4 .3 . 1 ]deca-2 2 »2 32 ,4 ,7 - t r i e n y l c a tio n (E quation 16 ). A dd ition of o th e r e le c tro p h ile s
H ^ H
FS03H-SQaClF
-128
(16)
13
(22) M. R oberts , H. Hamberger, and S. W inste in , I b i d . , §2, 6}b6 (19T0).
(23) G. Schrc&er, U. Frange, B. F u tze , J . T h io , and J . F. M. Oth, Chem. B e r ., lOfr, 3^06 (1971).
v l th subsequent quenching by a co u n te r-Io n produces various mono- and d l -2 3
s u b s ti tu te d b io y c lo t>l|'.3 .1 1 d e c a -2 ,U ,8 -tr ie n e s (E quation IT ).
E le c tro p h i l ic a d d it io n t o 7 -e u b s t itu te d te t r a e n e s th e o r e t ic a l ly can
produce fo u r Isom ers (E quation l 8 )j p roduct i s o la t io n however show*24
t h a t th e re a c t io n s proceed w ith la rg e e le c t ro n ic c o n tro l. With th e 7~*
(2lf) g. Schroder* U. P range, and J . F. M. Oth, Chem. B e r ., 105, 185^ (1972).
bromo- and 7 -a c e ty l d e r iv a t iv e s , re a c t io n w ith f lu o ro su lfo n ic a c id f o l
lowed by quenching w ith m ethanol-sodium carbonate p rov ides p ro d u cts r e s u l t -
ing from re a c tio n p a th s l 8c and d (Equation 19). W ith th e 7-m ethyl-
1) FSO3H
2) CH3OH>>
R
OCH3
R (19)
R c -B r, _COOCH3
24te t r a e n e , re a c t io n occurs exclusively v ia p a th 18a (E quation 20).
Chlcr o su lfony l iso cy an a te has Been re a c te d v i th a v a r ie ty o f s i ib s t l -
tu te d b icy c lo [4 .2 .2 3 d e ca -2 ,U ,7 * 9 -te trae n es . With 7-m onosubstitu ted t e t r a -
enes, isom eric p ro d u c ts r e s u l t from a d d itio n o f th e u n ip a r t ic u la te b ip o la r 25
e le c tro p h i le (E quation 21 ). For 7 * 8 -d isu b s titu te d t e t r a e n e s , v a rio u s
(25) L. A. P aque tte and M, J , B roadhurst, J . Org. Chem., %8 , 1886 (1973)*
(20)
CH3
16
r e s u l t s occur (E quation 22). When 7-m ethoxy-8-m ethyltetraene (R i = -OCH3 ,
NH
+
IV(22)
VI
R2 « -CH3 ) r e a c ts , a m ixture o f isomers IV and V r e s u l t s , vhereas th e 7 ,8 -24
d ipheny l d e r iv a tiv e forms isom er VI e x c lu s iv e ly .
The above p ro d u c ts a re p o s tu la te d t o he produced by 1 ,2 -c y c lo a d d itio n
to form {3-lactams, r in g opening t o z v i t t e r lo n ic bishomobropylium ions, and
c lo su re t o p ro d u c ts (E quation 23)*
ClS0aN=C»0
OaCl
(23)
Products
RESULTS AND DISCUSSION
The sy n th e s is , chem istry , and sy n th e tic u t i l i t y o f b i c y c lo p . 2 .2 Jde ca-
2 ,^ ,9 - tr ie n -T -o n e and i t s d e r iv a tiv e s have p re s e n tly been in v e s tig a te d .
F a c ile sy n th e s is o f t h i s system i s made p o s s ib le by th e e a r l i e r p re p a ra tio n
( 26) T. A. Antkowiak, Ph.D. D is s e r ta t io n , The Ohio S ta te U n iv e rs ity , Columbus, Ohio (1968).
in t h i s la b o ra to ry o f b i c y c l o ^ . 2 . l]n o n a -2 ,U, 7 - t r ie n -9 -one in h igh y ie ld
from c y c lo o c ta te tra e n e d ian io n and dim ethylcarbam oyl c h lo rid e (E quation 2I4-).
0 II
+ (CHaJaNCCl
B icy c lo [l* .2 .2 ]d e ca -2 ,lf ,9 -tr ie n -7 -o n e r e a c ts v i th excess diazomethaneo 27in m ethano l-ch lo ro fo rm -ether a t 0° v i th l i th iu m ch lo rid e c a ta ly s t t o
(27) A m o d ifica tio n o f th e method of M. S t o l l and W. S c h e rre r , Helv. Chim. A cta, 23, 9^1 ( 191*0 ) .
g iv e b ic y c lo [4 .2 .2 ]d e c a -2 ,U ,9 - tr ie n -7 -o n e ( l , 50- 85^) and sp iro [b ic y c lo -
Ifl
[U .2 .1 3 n o n a -2 ,lf ,7 - tr ie n -9 j2 , -o x iran e 3 (2^ 15-50?) (E quation 2 5 ). Isom ers
CHs N2-n2 3
105
+ \ \ (25 )
1 and 2 may "be se p a ra ted by p re p a ra t iv e g le . The s t r u c tu r e o f 1 i s e s ta
b l is h e d by i t s com bustion a n a ly s is and s p e c t r a l p ro p e r t ie s in c lu d in g in f r a re d
a b so rp tio n a t 1700 cm_1j u l t r a v i o l e t a b so rp tio n maxima in e th a n o l a t l tT̂ 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 a t C-2, -3 , -U, - 5, -9 , -1 0 ) , 3 -5 (m, IK, H a t C-6 ) ,
3 .0 (m, 1H, H a t C - l ) , and 2 .55 (d v i th a , 2H, H a t C-8 ) j and mass spec
t r a l a b so rp tio n , m/e = 1k6, f o r i t s p a re n t ion . Ketone 1 f u r th e r forms
th e expected sem icarbazone (3, rap 199* 5“200 . 5° ) , oxime (mp 131- 132° ) , and28
2 ,U -d in itropheny lhyd razone (rap 221- 222.5 ) d e r iv a t iv e s o f p ro p e r combus
t i o n a n a ly s is .
(28) Carbonyl d e r iv a t iv e s v e re p rep a red acco rd ing t o th e p ro ced u res of R. L. S h rin e r and R. C. Fuson, f*Fhe S ystem atic I d e n t i f i c a t io n of O rganic Compounds," 3 rd e d . , W iley, New York, N .Y ., 19^5*
Ketone 1 hydrogenates in e th a n o l w ith 5? p a llad iu m on carbon a s c a ta
l y s t t o form b icy c lo [J f .2 .2 ]d ecan -7 -o n e (]*, 9 5 ? ), mp 155-157° (E quation
2 6 ). The s t r u c tu r e o f ke tone 4 i s confirm ed by i t s in f r a re d a b so rp tio n a t
1720 cm"1, nmr a b so rp tio n a t 6 2 .3 (d imposed on m, ^H, H a t C - l, 6 , 8 ) ,
and 1 .7 (m, 12H, H a t C-2, -3 , -k , -5# -9 t and -1 0 ) j and i t s mass s p e c tr a l
19
nf n3 Ha >
-
10$ p a -0 \ y
CHaNa
Ha 596 Pd-C
(26)
p a re n t ion (m/e) o f 152. Ketone 4 i s a ls o c h a rac te rize d as i t s 2 ,4 -20
d in itropheny lhydrazone , (mp 1T9- 5 -181°), vh ich has th e p ro p e r mass spec
trum (m/e t= 332) and combustion a n a ly s is . B icyc lo [4• 2 .2]decan-7-one semi
carbazone ( 5) i s p repared in e th an o l-w ate r as v h i te c ry s ta ls (E quation5
26) ( 6096, mp 208-210°, l i t mp 205-207°). F u rth e r p u r i f ic a t io n o f £ from
5096 aqueous e th an o l produces th e pure d e r iv a tiv e v i th p ro p er combustion
a n a ly s is and mass spectrum (m/e = 209) , mp 220- 222° .
Ketone 4 vas p repared independently from b icy c lo [4 .2 .1 ]n o n an -9 -o n e29
(6 ) . B icy c lo £ 4 .2 .1 3 n o n a -2 ,4 ,7 -trien -9 -o n e hydrogenates in e th a n o l over
(29) C. D. Gutsche and T. D, Smith, J . Amer. Chem. S oc ., 82, 406? ( i 960) .
596 pa llad ium on carbon to ketone 6 (8596) , mp 98- 101° ( l i t mp 109- 111° )
20
(Equation 26 ). Ketone 6_ i s c h a ra c te riz e d by i t s in f ra re d ab so rp tio n a t 29 ~
I 7U0 cm"1 ( l i t 1737 cm"1), mass spectrum (m/e « 138) , and nmr abso rp tions
a t 5 2 .3 and 1 .55 (m superimposed on m). R eaction o f <5 w ith excess
diazom ethane in e ther-m ethano l a t 0° f o r 5 days y ie ld s ketone U (K # , Equa
t i o n 26). S a tu ra ted ketone ^ p re p a re d in t h i s manner i s id e n t ic a l gas
ch rom atograph ica lly and s p e c tra l ly v i t h th e p roduct p repared by hydrogena
t i o n o f 1 (E quation 26).
The s t ru c tu re o f epoxide 2 1b assigned from i t s combustion a n a ly s is ,
s p e c tra l p ro p e r t ie s in c lu d in g in f ra re d ab so rp tio n s a t 960, 860, and 7^5 cm"1,
and nmr ab so rp tio n s a t 6 6 .1 (m, 6H, H a t C-2, -3 , -^ , and - 3 ) , 3*3 (d ,
2H, H a t C-9 and -1 0 ), 3 .0 ( s , 2H, H a t C-21)# and 2 .75 (m, 2H, H a t C -l
and - 6 ) , mass spectrum [m/e <= 1^6), and i t s chem ical o r ig in . According to ao
p rev io u s vo rk , n u c le o p h ilic a d d itio n to b icy c lo [l* .2 . 1]nona-2 ,U ,7- t r i e n - 9 -
(30) T. A. Antkowiak, D. C. Sanders, G. B. T r im its is , J . B. P re s s , and H. S h ech te r, ib id . t 9j£, 5366 (1972).
one i s s t e r i c a l l y d ire c te d by th e la c k of s t e r i c h indrance on th e s id e o f31
th e carbonyl group fa c in g th e tvo -carbon b rid g e . Thus, re a c tio n v i th
(31) M olecular models r e v e a l th a t b ic y c lo [4 .2 .1 ]n o n a -2 ,U ,7 -tr ie n -9 -o n e i s a h ig h ly s t r a in e d r i g id compound in v h ich th e C-7 and -8 o le f in ic bond i s alm ost cop lanar v i th C - l, - 6, and -9 1 th e p lane o f C -l, C-6 . and C-9 i s — 60° ou t o f th e p lan e o f th e s tra in e d p la n a r C-2, -3# -&# and -5 d iene m oiety in vh ich i t s C-C bond ang les a re ~ 133°.
p h en y llith iu m , m ethyl magnesium brom ide, and sodium borohydride a l l occur
by n u c le o p h ilic approach from th e C-7 and -8 monoene s id e o f th e m olecule
21
to form th e 9 -pheny l, 9-m ethyl, and p a re n t syn-9 -hyd roxyb lcyc lo [^ .2 . 1 ]-32
nona-2 , l f ,7- t r l e n e s , r e s p e c tiv e ly . By analogy, ketone 1 and epoxide 2
(32) B icyclo[U .2.1]nona-2,U ,7“trien ea v ith the 9-subBtituent on the side o f the diene bridge are denoted as syn.
a re formed by n u c le o p h ilic approach o f diazomethane from th e l e s s e r h indered
a n t i - s id e o f th e b ic y c lo [4 .2 .1 ] tr ie n o n e form ing th e z v i t t e r io n ic interm e
d ia te 7 t vh ich c o lla p se s t o p roducts (E quation 27).
Ketone 1 vas i s o la te d p re p a ra tiv e ly from th e crude diazomethane r in g
expansion r e a c t io n m ixture by ( l ) fo rm ation and se p a ra tio n o f th e sem lcar-
(E quation 28) o r more advantageously by ( 2 ) r e a c t io n of th e crude r in g
expansion product v i t h G ira rd 's Reagent *P in re f lu x ln g a c e t ic a c id -e th an o l-
v a te r and h y d ro ly s is o f th e v a te r so lu b le adduct v i th co n cen tra ted hydro
ev acu a ted tu b e fo r 21 h r r e s u l t s in fo rm atio n o f m ethanol, nap h th a len e (60$)
and 2 -m ethoxynaphthalene (30$ ) , and re c o v e ry o f m ethoxy te traene 1£ ( 10%)
(E quation 1+3) - T herm olysis o f 1 £ p ro b ab ly occu rs v ia an a llow ed in te r n a l
200 OCH3+ CH3OH + H2
(1+3)
D ie ls -A ld e r r e a c t io n and d isa llo w e d opening t o t h e c !b -9 j 10-d ih y d ro n ap h th a l
ene d e r iv a t iv e which th e n a ro m a tiz e s (E q u a tio n hU). P a th a i s fav o re d
o v e r p a th b by about 2 : 1 . 2 -M sthoxynaphthalene was i d e n t i f i e d by com parison
OCII3
-CH3OH
OCH3
33* V
V o c H a
39
o f i t s nmr, i r , and mixed m elting p o in t v i th a n a u th e n tic sample p repared
from 2 -naph tho l, sodium hydride and m ethyl io d id e in dlmethylformamide (89^).
Ketone 1 may a ls o h e fu n c tio n a llz e d in th e C-6 p o s i t io n v ia i t s eno l.
When 1 i s re f lu x e d in a c e t ic a c id c o n ta in in g one eq u iv a len t o f le a d t e t r a
a c e ta te , a n t l - 8 -ace to x y b lcy c lo [4 .2 .2 ]d ec a -2 ,b , 9 -tr le n -T -o n e ( 26) i s quan
t i t a t i v e l y formed as p a le yellow c r y s ta l s , hp 9lt-96° (0.0U mm), rap 81-82°
(E quation 1+5)* Combustion a n a ly s is , mass spectroscopy (m/e = 20b), in f ra re d
0
26
a b so rp tio n a t 17^0 f o r carbonyl s t r e tc h in g and 1220 cm"1 f o r oxygen-
carbon s t r e tc h in g , and nmr ab so rp tio n s a t 6 9*9 (m, 6h, H a t C-2, - 3 , -k,
-5 , -9 , and -1 0 ) , 5.35 (m, 1H, H a t C -8), 3 .6 (m, 2H, H a t C -l, - 6 ) , and
2 .0 ( s , 3H, m ethyl C-H) confirm th e s t ru c tu re of 26. The ste reo ch em istry i s
a ssigned on th e b a s is o f a p robab le r e a c t io n mechanism (Equation U6) in v o l
v ing ( l ) carbonyl oxygen c o o rd in a tio n v i th le a d te t r a a c e ta t e and concommltant
/ 0Ac
0Pb(QAc)gffiD Pb(QAc) 3
-Pb(0Ac),QAc0
40
ex p u ls io n o f a c e ta te and hydrogen io n s t o produce e n o l le a d IV complex g j
and (2 ) a t ta c k o f ZJ_ "by a c e ta te io n from th e l e s s e r h indered s id e (a n t i
t o th e d iene b r id g e ) t o produce 26 (E quation 4 6 ). In te rm ed ia te 27 may a ls o
c o lla p s e t o 26 v ia a c y c l ic p ro c e ss o c cu rrin g fav o ra b ly from th e a n t i
d i r e c t io n .
A ttem pts t o p re p a re 8 -h y d ro x y b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e from
aoetoxyketone 26 v ia a c id -c a ta ly z e d t r a n s e s t e r i f i c a t i o n f a i l e d . R eflux ing
26 in m ethanol v i t h £ - to lu e n e s u lfo n ic a c id a s c a ta ly s t q u a n t i ta t iv e ly p ro
duces syn- and a n ti-8 -m e th o j{ y b ic y c lo [4 .2 .2 ]d ec a -2 ,4 >9 - tr ie n -7 -o n e s ( 28 and
2 j>) a s a 93 :7 m ixture (E quation 4 7 ) . The s t r u c tu r e s o f 28_ and 2 ^ a re a ss ig n ed
0
' from in f r a re d a b so rp tio n s a t 1720 cm-1, nmr a b so rp tio n s a t 6 5 .8 (m> 6h, H
a t 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, m ethyl C-H), mass s p e c tra (m/e = 176) and com
b u s tio n a n a ly s is . The m ajor isom er i s b e lie v e d t o be th e syn-methoxy-
k e tone 28 on th e b a s is o f m ech an is tic p r in c ip le s (E quation 4 8 ); a l i k e l y
p a th t o 28 invo lves fo rm atio n o f m ethy lhem lketal 30 , e lim in a tio n o f w a ter
t o g ive 7 -ace to xy -8 -m ethoxyb icyc lo [4 .2 , 2 ]d eca-2 , 4 ,7 ,9- te t r a e n e (31 ) , t r a n s
e s t e r i f i c a t i o n form ing th e 7-hydroxy-8-m ethoxy te traene £2 , and ta u to m e ri-
z a t io n o f e n o l 32 v ia a t t a c k o f a p ro to n from th e l e s s e r h in d ered a n t i -
0II
5°
HO.
52
HaO
£L
u _a H
CH30 - p Y
O
Ul
OCCH3
m
s id e . Ketone 28 i s th e major p ro d u c t. R eaction from th e syn-s id e produces
th e minor p roduct. Methoxyketone 28 ̂ is fu r th e r c h a ra c te r iz e d as i t s 2,U-
d in itropheny lhydrazone o f p roper combustion and mass s p e c t r a l a n a ly s is
(m/e « 356) .
A cid -cata lyzed h y d ro ly s is o f acetoxyketone 26 f a i le d . When 26 i s
h e a ted in d im ethylform am ide-vater f o r 8 h r v i t h j> -to lu en esu lfo n ic a c id , 2£
i s recovered (83%). The u n id e n tif ie d minor p ro d u c ts shoved arom atic
n u c le a r magnetic resonances.
B ase-cata lyzed e n o liz a t lo n o f 1 provides f o r f u r th e r fu n c t io n a l iz a -
t l o n a t C-8. R eac tion o f 1 v i t h 10 eq u iv a len ts o f potassium t-b u to x id e and37excess iso au y l n i t r i t e i n t -b u ta n o l gives b ic y c lo [4 .2 .2 ]d ec a -2 ,4 ,9 - t r i e n -
42
7, 8-dione monoxime (3J>, 6yf>) (Equation 1+9)* The yellow so lid , mp 178-178.5°,
i s pur i f ia b le in methylene chloride-hexane and i s characterized hy conibuB-
t io n and m ss sp ec tra l (m/e = 175) analyses, infrared absorptions at 3300#
N-OH
t-BuO ®K®
t-BuOH isoam yl n i t r i t e
(49)
a(57 ) A m o d ifica tio n of th e method of P . L itvan and R. Robinson, J . Chem.
S o c ., 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 -1 0 ), 4 .3 (dd, 1H, H a t C - l ) , and 3 .7 (m, 1H, H a t C-6 ) .
Oximinoketone i s converted by o-phenylenediam ine in a c e t ic ac id t o
th e qu inoxaline o f b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 > 8 -d io n e (j54)> np 194*5-
195° (E quation 50). The quinoxaline i s id e n t i f ie d by i t s in f ra re d and masB
s p e c tr a l p ro p e r t ie s (n /e = 232) , p roper combustion a n a ly s is , and nmr
NOH
a NHa
NHa\\ (50)
S t
a b so rp tio n s a t 6 8 .0 2 and 7 .6 7 (two m u lt ip le ts , H on arom atic n u c leu s),
6.1*7 (m, 2H, H a t C-2, -5 ) , 6 .0 2 (m, 2H, H a t C-9, -1 0 ), 5-82 (m, 2H, H
a t C-3, - 4 ) , and 1*.35 (n# 2H, H a t C -l, - 6 ). P ro ton assignm ents f c r Jjf
a re based on double i r r a d ia t io n ) i r r a d ia t io n o f th e m u ltlp le t a t 6 1*.35
(H a t C - l , - 6 ) causes s im p lif ic a tio n o f th e m u lt lp le t a t 6.1*7 and c o llap se
of th e a b so rp tio n a t 6.02 t o a s in g le t .
Comparison o f th e nmr ab so rp tio n s o f qu inoxaline %hj b ic y c lo [4 .2 ,2 ] -
deca-2 ,lf,7>9“‘te tra e n e (l& ), and 7 ,8 -d icarbom etho j^b icyclo [l* .2 .2 ]deca-2 ,lf,7> 9- la
te t r a e n e (39 ) shows th e la rg e in d u c tiv e e f f e c t o f th e qu inoxaline m oiety.
.82
6 5*86 -s? 6.026 6 . 12^ 6 3 .15
'As expected from t h e i r s im i l a r i t i e s in symmetry, lj*, and d isp la y
id e n t ic a l l in e shape p a tte rn s in th e nmr of th e v in y lic reg io n . D ie s te r
35, a r e l a t i v e ly e le c tro n d e f ic ie n t t e t r a e n e , shows s iz e a b le downfieM
nmr s h i f t s fo r p ro to n s a t C - l , - 6 , -2 , -5 , -9 , and -10 (Table I I ) r e l a t i v e
t o th e p a re n t lA (O .65, 0 .29 , and 0 .35 6, r e s p e c t iv e ly ) . Q uinoxaline 3j*
re v e a ls even g re a te r dow nfield s h i f t s fo r such p ro to n s ( 1 .20 , O.35, and
0 .52 6 u n i t s , r e s p e c t iv e ly ) . These s h i f t s probably stem from in d u c tiv e
e f f e c t s s in c e they f a l l o f f w ith d is ta n c e from th e s u b s ti tu e n t; n e ith e r
3|f nor show any n o tic ea b le nmr s h i f t s f o r t h e i r p ro to n s a t C-3 and -If.
Uh
A ttem pts t o co n v ert oxlm inoketone ^ t o b ic y d o [ 4 .2 .2 ] d e c a - 2 ,4 ,9 -38
t r i e n - 7 *8 -d io n e ( 36 ) f a i l e d ; r e a g e n ts such a s th a l l iu m t r i n i t r a t e , le a d3 9 4 0
t e t r a a c e t a t e , sodium b i s u l f i t e , and le v u l ln lc a c id d id n o t cause con-
( 38 ) A. M cKillup, J . D. H unt, R. D. N aylor, and E.- C. T a y lo r , J . Amer.Chem. S o c ., §3/ **918 (1971 ).
(39) S . H. P in e s , J . M. Chemerda, and M. A. K ozlow ski, 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).
v e rs io n o f 22. t o d ik e to n e (E q u atio n 51). A ttem pted c o n v ers io n o f oxim ino-
k e to n e 22. ^ 7 -d ia z o b ic y c lo [U .2 . 2 ]d e c a -2 , k , 9 - t r i e n - 8 -one (^T^) u s in g a lk a l i n e
ch lo ram ine a ls o f a i l e d (E q u a tio n 51*)•
NOH
■*— W - (51)
5£ 51Ketone 1 may a ls o b e f u n c t io n a l iz e d a t C-8 by b a s e -c a ta ly z e d condensa
t i o n v i t h m ethy l fo rm a te . When 1 i s exposed t o fo u r e q u iv a le n ts o f
sodium m ethoxide and excess m ethy l fo rm ate i n e th e r , 8 -form ylb icyclo[l+ . 2 . 2 ]-
d e c a -2 ,h ,9 - t r ie n -7 - o n e (3 8 ) fo rm s, mp 58-57°* 95^ y ie ld (E quation 52).
Maes s p e c t r a l d a ta (m/e = 17*0* p ro p e r com bustion a n a ly s is , in f r a r e d c a r
bo n y l a b s o rp tio n s a t 1660 and 1580 cm**1, and nmr a b so rp tio n s a t 6 8 .1 (a ,
1H, a ld e h y d ic C-H), 5 .9 (®* 7H, H a t C-2, - 3 , -h , - 5, - 8 , -9 , and -1 0 ),
and 3 .5 (m, 2H, H a t C - l , - 6 ) su p p o rt th e s t r u c t u r a l assignm ent o f 28.
CH
h 5
(52)
Fornylketone ^Q_ i s converted t o 2 ,4 -d ia z a tr ic y c lo [5 .4 .2 .02 ' Q3 tr id e c a -,̂ , . 4 1
2 , 5 . o, 10, 12-pentaene (39 ) by anhydrous hydrazine in re f lu x ln g e th a n o l
(E quation 53)• P yrazo le 39 . formed in 86/6 y ie ld , i s a yellow s o l id , mp
13
10
H
(53)
11
22.
(U l) Method o f W. E. Parham and J . P . Dooley, J . Amer. Chem. S o c ., 89* 985 (1967).
106-107° , w ith in f ra re d a b so rp tio n a t 3250 cm-1 , nmr ab so rp tio n s a t 6 9#25
(broad s , 1H, >N-H, s h i f t is c o n ce n tra tio n dependent, d isap p ears upon pgO
a d d it io n ) , 7 .15 (&> 1H, H on C -5), 6 .2 and 5 .7 (m u lt ip le ts , 6h, H a t C-8,
-9 , -10 , -11 , -12 , and -1 3 ), and if.O (m, 2H, H a t C -l and - 7 ) , a p roper
mass s p e c t r a l p a re n t ion and a s a t i s f a c to r y combustion a n a ly s is . P o s itio n s
o f th e double bonds in th e p y razo le r in g o f ^2. o re p robably d e lo c a liz e d
as shown.
R eaction o f form ylketone 38 v i th to s y l a z id e and tr ie th y la m in e in4 a ’
m ethylene c h lo r id e a t 25° g ives 7-d iazobicyclo[l+ . 2 .2 ]d ec a -2 ,k ,9 - t r ie n -8 -
(1*2) In a m odified procedure o f th a t d esc rib ed by M. R eg itz and J . R u te r, Chem. B e r ., 101, 1263 (1968).
one (37 ) (E quation 5*0, a yellow s o l id in 55$ y ie ld . D iazoketone 3 £ ex”
0
OrHrSOgNa
21h i b i t s in te n se in f ra re d ab so rp tio n s a t 2150 fo r d iazo group and 1650 cm-1
fo r carbonyl group s t r e tc h in g , mass s p e c t r a l ion a t Ikk (P-Ng), and nmr
ab so rp tio n s a t 8 5*9 (®j 6h, H a t C-2, -3 , -5* -9 , and -10) and 3»6?
(m, 2H, H a t C -l, - 6 ) .
P h o to ly s is o f d iazoketone 37 r e s u l t s in W olff r in g c o n tra c tio n . Thus
i r r a d ia t io n o f 37 i n d io x an e -v a te r g ives b i c y c l o . 2 . l]n o n a -2 ,^ ,7 - t r i e n -
sy n -9 -carb o x y lic a c id (U0, 6l% y ie ld ) (E quation 55)* Syn-carboxy lic ac id
1*7
(1*3) D. C. S an d ers , Ph.D . D is s e r ta t io n , The Ohio S ta te U n iv e rs ity , 1972.
1*0 i s i d e n t i c a l ( i r , m e ltin g p o in t , and nmr) v i t h t h a t p rep a red hy chromic
a c id o x id a tio n o f b ic y c lo [ l* .2 . 1 ]nona-2 ,l* ,7- t r i e n - s £ n - 9-carboxaldehyde.
To d e te rm in e th e hom ogeneity o f th e c rude p h o to p ro d u c t, c a rb o x y llc
a c id 1*0 was t r e a t e d v i t h ex cess d lazom ethane i n e th e r . The r e s u l t in g p ro
d u c t , m e th y lb icy c lo [ 1+. 2 . 1 ] nona-2 , 1+, 7 - t r l e n - syn- 9 -c a rb o x y la te ( 1*1 , 93%)
(E q u atio n 56 ) i s a v h i te s o l i d , mp 27-29°# bp 6 6 .5 ° (0 .0 5 mm) and i s homo
geneous by g lc a n a ly s is . The s t r u c tu r e o f 1*1 i s confirm ed f u r th e r by i t s
in f r a r e d ca rb o n y l a b so rp tio n a t 1720 cm-1 , mass s p e c t r a l p a re n t io n (m/e =
17^)# p ro p e r com bustion a n a ly s i s , and nmr a b so rp tio n s a t 6 5«9 (a , 1*H, H a t
C-2, -5 , -1*, and -5)# 5 .15 U , 2H, H a t C-7, - 8 ) , 5 .5 (b , m ethyl C-H),
superim posed on 3 .3 (®» H a t C - l , - 6 , -9 , t o t a l 6h ) .
CH3OC
(56)
1*1
The m e c h an is tic a s p e c ts o f th e W olff r i n g c o n tr a c t io n and h y d ra tio n*
p ro c e ss a llo w th e p r e d ic t io n t h a t 1*0 i s th e oyn-c a rb o x y llc a c id (E quation
57 ) . ThuB th e c a rb e n ic In te rm e d ia te 1*2 from gT. (E q u a tio n 57) isom eriees
t o k e ten e k%_ w hich h y d ra te s by p ro c e ss e s in w hich a p ro to n i s d e liv e re d t o
C-9 from th e a n t i - d i r e c t i o n . .
P r o t ic decom position o f d lazoketone a ls o r e s u l t s In profound s t r u c -
y ie ld ia m ix ture o f exo- and endo-2-acetoxyb lc y c lo f 5 .2 . l ld e c a -3 , 5, 8 - t r ie n -
10-ones (44 and 4;?) (E quation 58 ) , r e s p e c t iv e ly . D i s t i l l a t i o n removes th e
0
minor e n d o -ace ta te 4j^ from jj4. The s t r u c tu r a l assignm ent o f 44 i s supported
by in f ra re d ab so rp tio n s a t 1760 and 1740 cm-1 f o r e s te r and ketone carbonyl
s t r e tc h in g , u l t r a v io l e t a b so rp tio n maxima in e th a n o l a t Xmax 200, 225,
and 285 nm (cmrtv. = 6080, 4000, and 600, r e s p e c t iv e ly ) , mass s p e c t r a l p a ren t
ion (m /e) o f 204, and p ro p e r combustion, a n a ly s is . Nmr ab so rp tio n s a t ( 5*9
(m, 6H, H a t C-3, -4 , -5 , -6 , -8 , and - 9 ) , 5 .00 ( t , 1H, H a t 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) a ls o support th e s t r u c tu r a l assignm ent o f 44. Double i r r a d ia t io n o f* ♦
th e ab so rp tio n a t 6 3 .05 s im p lif ie s th e t r i p l e t a t 5*00; i r r a d ia t io n of
th e t r i p l e t causes s im p li f ic a t io n o f th e a b so rp tio n a t 3*05* T his decoup-
t u r a l rearrangem ents. Thus £7 r e a c ts w ith g la c ia l a c e tic a c id a t 25° t o
IIch3coh
! £
l in g In d ic a te s t h a t th e p ro to n bound t o carbon s u b s ti tu te d by a ce to x y l i s
ad jacen t t o a b ridgehead p ro to n .
Exo ste reo ch em istry a t C-2 o f 44_ i s assigned on th e b a s is o f m echanistic
co n s id e ra tio n (E quation 59); i n i t i a l p ro to n d e liv e ry t o d lazoketone p ro -
*
51 46
« 0 // CH3CO-^a I*
47
a
CH3CO"
b ab ly occurs from th e l e s s h indered a n t i - s id e o f th e dlazoketone t o form
th e p ro to n a ted d iazo in te rm e d ia te 46. N itrogen probably leaves v i t h back
s id e s t a b i l i z a t io n by th e monoene (C-9> -10) b r id g e v i th subsequent c o l
lap se t o th e bishom otropylium ion 47* Combination w ith th e c o u n te r-io n i s
more l ik e ly t o occur from th e le s s h indered exo-s id e o f c a tio n 47 v ia p a th a
(E quation 59) to produce th e exo-acetoxyketone 4U as th e major p ro d u c t.
A ttack from th e endo-s ld e o f ljT i s much le s s p robab le due to s t e r l c I n te r
fe ren ce o f th e monoene b rid g e and i s a minor p ro cess .
An a l te r n a t iv e p roduct from decom position o f d lazoketone £7, by a c e tic
a c id could r e s u l t from m ig ra tio n o f th e d iene b rid g e to th e carbonlum ion
formed a t C-8 (Equation 60 ). Such m ig ra tio n would g ive bishom otropyllum
ion {(8 in a manner analogous t o e le c t r o p h l l lc a d d itio n s t o b ic y c lo p i .2 ,2 ] -
In o rd er to prove th a t acetoxyketone Ml i s formed in s te a d o f Ml
was hydrogenated in e th a n o l w ith pa llad ium on carbon a s c a ta ly s t t o p ro
duce exo -2 -ace toxyb icyclo [5 .2 .1 ]decan-10-one (^0 ) , mp Mr-M?0* In 73^ y ie ld
(Equation 6 l ) , The s t ru c tu re o f acetoxyketone £0 i s assigned from i t s
51(60)
11. cibco'
&
d e ca -2 ,4 ,7 > 9 -te tra e n e s . F in a lly , com bination o f a c e ta te io n w ith M3
would r e s u l t in exo-7 -a c e to x y b lc y c lo rM 3 .n d e c a -2 ,M 8 -tr ie n -1 0 -o n e ( Uj>).
51
p ro p er coribustion a n a ly s is , mass spectrum (m/e 210) and In f ra re d carbonyl
s t r e tc h in g frequency a t 1750 cm"1, and nmr d isp la y in g no o le f ln ic p ro to n
ab so rp tio n ) jjO was th e n sa p o n ifie d in sodium hydroxide-m ethanol t o exo-2 -
hydroxyb icyclo [5 .2 .l3decan -10-one (j?l) (E quation 6 l ) as c h a rac te rize d by
in f ra re d hydroxyl group s t r e tc h in g a b so rp tio n a t 3^50 and carbony l group
s t r e tc h in g a t 1730 cm**1, and by exac t mass measurement (m/e « 168) .
0OHPd/C
OHH
(61)
Hydroxyketone jSl i s ox id ized q u a n ti ta t iv e ly v i th chromium t r lo x ld e in
ace tone to b icy c lo [5 « 2 .1 ]d eean -2 ,1 0 -d io n e (£2) (E quation 6 l ) . The id e n t i ty
o f d ike tone i s confirm ed by i t s mass spectrum (m/e = l6 6 ) , i t s In f ra re d
carbony l s tre tc h in g a b so rp tio n s a t 1730 and 1700 cm- 1 , and by i t s p ro p er
com bustion a n a ly s is . D iketone £2 1b d is s im ila r in nmr, i r , and p h y s ic a l
p ro p e r t ie s t o b ic y c lo P ) .3 . 13decan-7 , 10-dione (35) p repared v ia re a c t io n o f44
1-m orpholinocycloheptene and a c ro y l c h lo r id e .
(UU) J . R. H argreaves, P. W, Hickm ott, and B. J . Hopkins, J . Chem. Soc. C, 592 (1969).
52
Diazoketone £ £ i s decomposed ra p id ly by hydrogen c h lo rid e t o exo-
2 -c h lo ro b ic y c lo [5 .2 .1 ]d e c a -3 ,5 ,8 - tr ie n -1 0 -o n e (£4) in 94^ y ie ld (Equation
62 ) . Although £4 i s to o l a b i le t o be c h a ra c te r iz e d com pletely , mass spec-
HC1
-Na(& )
z l a
t r a l (m/e e= 180) and ex ac t mass measurements, in f ra re d carbonyl group
s tr e tc h in g a b so rp tio n a t 1740 cm*1 and nmr ab so rp tio n s a t 6 5*9 (m, 7H> H
a t C-2, -5 , -4 , -5# -6 , -8 , and -9 ) and 5 .2 (m, 2H, H a t C -l and - 7 ) a l l
suppo rt th e s t r u c tu r a l assignm ent of £4. By m echanistic p r in c ip le s used
to account f o r th e form ation of acetoxyketone 44, ch loroketone £4 Is
assumed to have exo-s te re o ch e m is try a t C-2.
For f u r th e r p roo f o f th e r in g system of ch loroketone, £4 was hydrogenated45
in a b so lu te e th a n o l over pa llad ium on carbon to b icy c lo [5 .2 .1 ]decan -10 -one
(££ , 6 lf ) (E quation 65 ) . The ketone i s c h a ra c te r iz e d by i t s in f ra re d ab-
(45) C. D. Gutsche, T. D. Smith, M. F. S loan , J . J . Q uarles van U fford, and D-. E. Jo rdan , J . Amer. Chem. S o c .. 80, 4117 (1958).
H " i_ H a _____
Fd/c (63)
I
5345
B orption a t 1730 cm-1 ( l i t 1731 cm"*), nmr showing no v in y lic p ro ton
a b so rp tio n and ex ac t mass (m/e «= 152). The s t ru c tu r e o f ketone £ £ i s con
c lu s iv e ly e s ta b lis h e d by conversion to b ic y c lo [5. 2 . l ]d e c a n -10-one 2 ,4 -
and shows no m elting p o in t d ep ress io n upon adm ixture v i th an au th e n tic4 6
sample o f 2 ,4 -d in itropheny lhydrazone £6 . Both sam ples o f ^ p o s s e s s ld en -
(46) The au thor v lsh e s to th an k Dr. C. D. Gutsche f o r supplying th e au thent i c sample in a pe rsonal communication, May 9» 1973*
t i c a l in f ra re d s p e c t r a l p ro p e r t ie s j th e sample o f p6 p repared from ch lo ro
ketone a lso g iv es th e p ro p er exact mass (m/e » 332) .
Chloroketone i s a ls o converted by s i lv e r a c e ta te in a c e t ic a c id
to a m ix tu re of ace to jy k e to n es M and 4 £ (E quation 64) in 53% conversion .
od in ltropheny lhydrazone (56 ) which m elts a t 175-176 ( l i t 176- 177. 5° ) ,
&
0 .
A2OCOCH3 \\ CHaCQaH
II
5^
The s p e c t r a l p r o p e r t i e s ( i r , nmr# and g lc ) o f th e p ro d u c t show t h a t th e
r a t i o o f Uj* and j+J5 v ia th e s i l v e r a c e ta te r e a c t io n i s e s s e n t i a l l y th e same
a s th e r a t i o o f 4k and o b ta in e d from decom position o f d lazo k e to n e 37
c a ta ly z e d by a c e t i c a c id .
A ttem pts t o p u r i f y ace to x y k e to n e W and c h lo ro k e to n e Jjjf by p re p a ra
t i v e g lc le d t o Cope rea rran g e m en ts . A cetoxyketone re a r ra n g e s t o endo-
6 - ( c i s - 2 t -ac e tO 3 g v in y l)- c i s -b ic y c lo r3 .3 .0 1 o c ta -3 j7 “d ien -2 -o n e ( g7 ) i n 93%
y i e ld a t a column te m p e ra tu re o f 225° (E q u a tio n 65 ) and ch lo ro k e to n e g4
c o n v e rts t o endo- 6 - ( c i s - 2 1 - c h lo r o v in y l) - c l s - b ic y c lo r 3 .3 .0~ |octa -3 .7~ d len -2 -
one
OCOCH3
//
c 6
m
' \ 0JXQCB9
i t SL
-(66)
f /
H
The s t ru c tu re of acetoxyketone 57 i s assigned in p a r t on in f ra re d ab
so rp tio n s o f an e s t e r carbonyl a t 1760 cm- 1 and an at, p -u n sa tu ra ted carbonyl
a t 1695 cm'1, uv ab so rp tio n in e th e r a t \ mav 210 nm (e = 31, 500) , a mass
s p e c t r a l p a re n t ion (n /e o f 204) and coribuBtion a n a ly s is . The nmr spectrum
of i s s u i ta b le f o r complete a n a ly s is by double i r r a d ia t io n experim ents
and i s describ ed a s fo llo w s: 6 7 .50 (dd , J = 6 ,3 , 1H, H a t C -4), 7 .14 (dd ,
J = 6 , 1 , IB, H a t C -2 ') , 6 .08 (dd, J = 6 , 1 .5 , 1H, H a t C -3), 5.80 and
5.50 (m u lt ip le ts , 2H, H a t C-7 and - 8 ) , 4 .69 (dd , J « 10, 6 , IB, H a t C - l ') ,
4 .14 ( t , J = 10, IB, H a t 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 m ethyl g roup). R e su lts o f double I r r a d ia t io n
a re summarized in T able IV. Comparison o f th e nmr o f t o th e model*7
compound, b ic y d o [ 3 . 3 . 0 ]o c t -3-e n e -2 -one (jjj?), v h ich shows nmr ab so rp tio n s
(47) S . Moon and C. R. Ganz, J . Org. Chem., 5%, 124l (1970).
a t 6 7 .3 (dd, J = 6 ,3 , 2B, H a t C -4), "5 .95 (dd , J « 6 ,2 , IB, H a t C -3),
and 3*S3 (®, 1H, H a t C -l) supports th e assignm ent t h a t £7 con ta ins th e
b icy e lo [3 .3 « 0 ]sy ste ra . Assignment o f th e c i s -s te re o c h e m ls try o f th e C -l* -
C-2' o le f in i s supported by th e nmr coupling co n stan t ( J s 6 Hz) f a r th e
p ro to n ab so rp tio n s a t & 7 .14 and 4 . 69 . T h is va lue i s w e ll w ith in accep ted
6 3 .23
& 5.95 ( J « 6 ,2 )
&
56
Table IV
Double I r r a d ia t io n o f endo- 6 - ( c l s - 2 1- Acet oxyv lny l)- c i s -
[3* 3 .0 1 o cta -3 j7 -d ien -2 -o n e (37)
Dicyclo-
r
•Ac
NMR, s h i f t i n 6
7 .50 7 .14 6 .08 5.80 5.50 4.69 4 .1 4
- 1* -6I r r a d i a t i o n H a t C
o f H a t C -4 -2* -3 -7 -8
3.80 3.46
-5 -1
-4 - + - - - -
-2 ' - - - - + +
-3 + - - - - -
-7 - - - + - +
-8 - - - + - +
-1 ’ - + - - - +
-6 - + - + +
-5 + - +•
- - +
-1 _ _ + + _ +
+
+
+
+
- no e f f e c t
+ p a t te r n s im p li f ic a tio n upon double i r r a d ia t io n0II
S h i f t o f CH3CO- a t 6 2 .10
48valueB fo r c l s - o le f ln lc protons ( j * 6-12 Hz) whereas i t i s far too
small fo r tra n s -o le f ln lc p ro to n s ( J = 12-18 H z).
(If8 ) H. M. S i lv e r s te in and G. C. B ass le r , "S pectrom etric I d e n t i f ic a t io n o f Organic Conpounds," Second e d it io n , John Wiley and Sons, I n c . , New York, N.Y., 1967*
The s t ru c tu r e o f £ £ i s f u r th e r e lu c id a te d upon i t s h y d ro ly s is by
aqueous t r i f l u o r o a c e t i c a c id to e n d o -6 - ( l '-o x o e th y l) -c is -b ic y c lo [3 .3 .0 ]“
o c ta -3 i7 -d len -2 -o n e (60) (E quation 67 ) in 75^ y ie ld . The s tru c tu re o f 60 i s
at- q S «II
V-OCOCH3 CHaCH60
c o n s is te n t w ith i t s ex ac t mass measurement (m/e = 162) , in f ra re d ab so rp tio n s
a t 1715 and 1700 cm"1 f o r aldehyde and at p -u n sa tu ra ted ketone s tre tc h in g ,
and nmr ab so rp tio n s a t 6 9 .80 ( s , 1H, H a t C - l ' ) , 7 .32 (dd , J » 6 , 2 .3 /
1H, H a t C-1+), 6 .02 (dd , J = 6 , 2 , 1H, H a t C -3)/ 5 .6 (m, 2H, H a t C-7,
- 8 ) , 3 .55 (m, 3H, H a t C -l, -5 , - 6 ) , and 2 .6 (b r d , 2H, H a t C -2 ') . The
coupling c o n s ta n ts and s h i f t s o f th e pro tons a t C-3 and -If a re a lso s im ila r
t o th o se of model compound b ic y c lo [3 .3 .0 ]o c t-3 -e n e -2 -o n e ( 59 ).
The s t ru c tu r e o f ch lo roketone £8 i s a ss ig n ed from i t s in fra re d carbony l
s t r e tc h in g a b so rp tio n a t 1700 cm-1, u l t r a v io le t ab so rp tio n in e th e r a t ^
210 nm (e = 31 , 300), mass spectrum (m/e = 180) , combustion an a ly s is and
nmr a b so rp tio n s a t 6 7-50 (dd , J = 9 , 2 , 1H, H a t C-lf), 6 .1 5 (m, 2H, H
a t C-3, - 2 ' ) , 5-90 (m, 2R, H a t C-7 and - 8 ) , If.55 On, 1H, H a t C - l ' ) ,
3 .7 lf (m, 2H, H a t C-5, - 6 ) , and 3 -^6 (m, 1H, H a t C - l) . W hile com plete
p ro to n assignm ent i s im p o ssib le by double i r r a d i a t i o n , p a r t i a l assignm ent
can be made; d eco u p lin g o f th e a b so rp tio n a t 0 7 -5 0 causes s im p l i f ic a t io n
o f th e m u l t ip le t s a t 6 .15 and 3 -7 ^ , d eco u p lin g a t 6 3 .b 6 s im p l i f ie s th e
s ig n a ls a t 5-90 , If .55, and 3*7^, and double i r r a d i a t i o n a t 6 3 -7^ r e s u l t s
In s im p l i f i c a t io n o f a l l o th e r a b s o rp t io n s . (The m ajor c o u p lin g o f th e
B lgnal a t 6 7 -50 ( J = 9 ) a g a in In d ic a te s t h a t th e e x o c y c lic o l e f in (C -l* ,
- 2 f ) o f ch lo ro k e to n e i s o f c i s - s te re o c h e m is try .
The r e a c t iv e con fo rm ations o f ace toxyke tone Mf and ch lo ro k e to n e jjjf
f o r Cope rea rran g em en t a re c o n s is te n t v i t h th e s t r u c tu r e s o f th e observed
p ro d u c ts . The two s ta b le c o n f ig u ra tio n s o f 4jf_ and jjU a s d e riv e d from
m o lecu la r models a re shown a s 6 l and 62. Of th e conform ers, 6 l i s l e s s
0
61
R b OCOCH3, Cl H
62
s t r a in e d and has th e g r e a te r m onoene-diene I n te r a c t io n . The o v e r a l l Cope
rea rran g em en t from iso m eric form 6 l f o r t h e ace toxyketone and c h lo ro
ke tone i s d e p ic te d in E q u a tio n 68. The r e a c t io n th e r e f o re i s expec ted
t o p roduce th e therm odynam ically more s ta b le c l s - r l n g J u n c tu re and c l s -
s te re o c h e m is try f o r th e e x o c y c lic o le f in .
59
&
44, RsOCOCHa
%kj R e d
H
- < x >i (
H
SJj R«0C0CH3
J§8, R=C1
Attem pts t o reduce ketone 1 v ia a W olff-K lshner re a c t io n f a i l e d to
produce b ie y c lo [4 .2 .2 ]d e c a -2 ,4 ,7 - tr ie n e (6f t ) . R ather, ketone 1 r e a c ts w ith
63
excess hydrazine and potassium hydroxide in e th y len e g ly c o l a t 170-200° t o
g ive 2 ,3 -d ia z a t r ic y c lo [6 .3 .1 .0 4 ,1 1 ]d o d e c a -2 ,5 ,9 - tr ie n e (64) in kTf y ie ld
along w ith s e v e ra l minor hydrocarbon p roducts t h a t were no t id e n t i f ie d
(E quation 69 ) . F y razo lin e 64 i s a w hite s o l id , mp 170-172°, o f mass spectrum
KOHROCHgL'HgOH
60
(m /e a l 6o) and v i t h p ro p e r com bustion a n a ly s i s . The p ro d u c t d is p la y s
I n f r a re d azo a b so rp tio n a t 1650 cm"1; I t s u l t r a v i o l e t spectrum shovs end
a b s o rp tio n ( \ maY 200 nm, = 3 , 700 ) and a b so rp tio n c o n s is te n t v i t h a4 9p y ra z o lin e (X ^ y 333 nm, «meoc *= 330)- The n itro g e n -c o n ta in in g p ro d u c t
(lf9) (a ) S. 0 . Cohen and R. Zand, J . Amer. Chem. S o c .» 8jf, $06 (1962) .(b ) M. S chvarz , A. B eso ld , and E. R. N elson, J . Org. Chem., 30.Zk25 (1965). ( c ) R. M. M o ria rty , l o l d . , 28. 23«5 U 963J.
f u r th e r d is p la y s nmr a b s o rp t io n s a t 6 6 .0 3 (m, 2H, H a t C-9, -1 0 ) , 3 .33
and 5 .03 (m, 3H, H a t C-lf, - 5 , and - 6 ) , lf.81f ( t , OH, H a t C - l ) , 2 .80 (m,
3H, H a t 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 ( s e p tu p le t , 1H, H a t C -12).
In fo rm a tio n concern ing th e s t r u c tu r e o f 61f_ i s o b ta in e d by nmr double
i r r a d i a t i o n and europium s h i f t re a g e n t s tu d ie s . Double i r r a d ia t io n o f
th e a b s o rp t io n a t 6 2 .8 0 s im p l i f ie s on ly th e a b so rp tio n a t 6 . 03; d eco u p lin g
o f th e t r i p l e t a t U.&f s im p l i f i e s th e s e p tu p le t a t 1.73* The europium
s h i f t r e s u l t s a re summarized in T able V. A ssignm ents o f th e p ro to n s a t
C - l and -If and C -U a re made baaed on t h e i r m agnitude o f s h i f t ; p ro to n s
c lo s e s t t o th e europium complexed a z o - lin k a g e shou ld have th e l a r g e s t
s h i f t . The o l e f in ic p ro to n s on C-9 and -10 and th e exo p ro to n on C-12
a re th e f a r t h e s t removed from t h e a z o - lin k a g e ; th e s e p ro to n s shov th e
l e a s t e f f e c t in t h e i r chem ical s h i f t s .
In a d d i t io n a l a tte m p ts t o e f f e c t i t s deoxygenation , 1 v as co n v erted by
h y d raz in e t o b ic y c lo [ 4 . 2 . 2 ]d e c a -2 , If, 9 - tr ie n -T -o n e hydrazone (65) in 9&f>
y ie ld (E q u a tio n 7 0 ) . Hydrazone 6£ shovs in f r a r e d a b so rp tio n s a t 3330 and
Table V
Eu(Fod)s Induced Chemical S h ift Bata fa r Compound #*
Photochem ical rearrangem ent o f ketone 1 was In v e s t ig a te d f o r p o s s ib le
f a c i l e s y n th e s is o f v a rio u s b ic y c l i c and t r i c y c l i c d e r iv a t iv e s . I r r a
d ia t io n o f ke tone JL in acetone th rough Vycor produces two Isom eric p ro -2 S
d u c ts along w ith 1 (10/6). The f lu x io n a l m olecule t r ic y c lo [ 5 - 5 .2 .0 ’ ] -51
d e ca -3 * 6 -d ie n -9 (l0 )-o n e (83 ) i s th e m ajor p roduct (68^> y ie ld , E quation-1 3183 ) . Ketone e x h ib i ts in f r a r e d carbony l s t r e tc h in g a t 1685 cm” ( l i t
(51) W. von E. D oering, B. M. F e r r i e r , E. T. F o s se l, J . H. H a r te n s te in ,M. Jo n e s , J r . , G. Klumpp, R. M. R ubin, and M. Saunders, T e t . , 23, 39^3 (1967).
1685 cm-1) , u l t r a v io l e t maxima in hep tane a t 200, 290, 300, 312, and 322
(®max B 7 ,^ 0 0 , 130, 105, 85, and 6 l ) and nmr a b so rp tio n s a t 6 3 .8 (m,
H a t C-3, - 1*, -6 , and -7 ) and 2 .5 (m, 6h , H a t C - l , -2 , -5 , -8 , and -1 0 ) .
The nmr o f 8 ^ i s tem pera tu re dependent) ke tone 8 ^ i s id e n t ic a l in a l l30
re s p e c ts t o an a u th e n tic sample p rep a red by r in g expansion o f b a rb a ra lo n es i
w ith diazom ethane.
The second i r r a d ia t io n p ro d u c t i s t e n t a t i v e l y assumed a s t r i c y c lo -
[ 5. 3 . 0 .0 2 ' 10]d eca -3 ,5 -d ie n -8 -o n e (8U, 12?>) (E quation 83) . Ketone 8U shows
10
hv
a
10
(83)
a 8U
In f ra re d carbonyl a b so rp tio n a t 1740 cm”1 ty p ic a l o f cyclopentanones,
p ro p er ex ac t mass (m/e *= 146) and nmr ab so rp tio n s a t 6 5 .9 (m, 4h, H a t
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 a t C -9), and 1 .5 (« , 2H, H a t C -l and -1 0 ). Ketone 84 does
no t form a tosylhydrazone d e r iv a tiv e in th e expected manner.
Form ation o f and 84 by p h o to se n s itiz e d i r r a d ia t io n o f ketone 1
may invo lve d l r a d ic a l 8£ (Equation 8 4 ). R eac tion v i th carbony l group
carbon C-7 produces d i r a d ic a l 86 which c o lla p se s t o ketone 8^ . Reac
t io n v i th th e C-9> -10 monoene b rid g e forms d i r a d ic a l 87 which may c o llap se
v i th carbonyl m ig ra tio n t o ketone 8jf.
I r r a d ia t io n o f ketone 1 in e th e r w ith Pyrex o p tic s produces ketone
§2, (W3%) and ke tone 8j* (27%). Photochem ical rearrangem ent of 1 u sin g
M ich ler' a ketone as s e n s i t i z e r and Pyrex o p tic s a ls o produces ketone 8£
in kk% y ie ld .
Ketone 8j5 r e a c ts w ith d i lu t e t r i f l u o r o a c e t i c a c id t o produce ketone 1
q u a n ti ta t iv e ly (E quation 85 ) . F u rth e r, r e a c t io n o f 83. and to sy lh y d raz id e
m s s Bpectrum. The nmr of a lc o h o l 86 is tem pera tu re dependent; th e absorp
t io n a t 6 5*1 s h i f t s to h igher f i e l d as te iqpera tu re in c re ases (6 if. 65 a t
80°) and to lower f i e l d upon co o lin g (ft 5*51 a t -2 5 °). P a r t o f th e m u lti-
p l e t cen te red a t 8 2 .3 a ls o s h i f t s w ith tem pera tu re (tow ard lower f i e l d
upon warming, h igher f i e l d on co o lin g ) h u t th e com plexity of th e ab so rp tio n
p rec lu d es f u r th e r a n a ly s is .
NaBH*
CH3OH
10
8
3
(87)
68
76
The p re se n t d is s e r ta t io n re p re se n ts a study o f sy n th e s is and some o f
th e chem istry o f b ic y c lo [4 .2 .2 ]d e c a -2 ,h ,9 - tr ie n -7 -o n e ( l ) and i t s d e riv a
t iv e s . I n i t i a l l y , p re p a ra tio n o f b ic y c lo [k . 3 .2 ]undeca-2 ,1* ,8 ,10-te traen-
7-one and study o f th e chem istry o f th e b ic y c lo [k .3 .2]undeca-2, U, 8 , 10-
te t r a e n - 7 - y l carhonlum ion , carban ion and carbene were a p o r tio n o f th e
goals o f t h i s re s e a rc h . A fte r t h i s phase o f th e re se a rc h had been i n i t i a
te d , th e b ic y c l ic [ ^ . 3 . 2 ] te t r a e n y l system was rep o rte d syn thesized from methoxy-sa
te tr a e n e 37. in e s s e n t ia l ly th e same manner a s p lanned in t h i s labo ra to ry*
(32) (a ) P r iv a te ly communicated from M. J . G o ldste in , November 26, 1971.(b) M. J . G o ldste in and S. A, K line, T e t . L e t te r s , IO89 (1973)•
52Because o f t h i s r e p o r t , con tinued s tu d ie s in t h i s a re a v e re abandoned; o th e r
a sp ec ts o f th e chem istry of th e b ic y c l ic [k .2 .2 ] system vere in v e s tig a te d .
There i s much y e t t o be lea rn ed about th e b ic y c lo [ ^ .2 .2 ] t r le n y l system .
Exam ination o f th e p ro p e r t ie s o f b ic y c lo [ lf .2 .2 ]d e c a -2 ,^ ,9 - tr ie n -7 -y l c a r
bene, carbonium ion and carban ion should p rov ide f u r th e r in s ig h t in to th e
in te rco n v e rs io n s and chem istry o f th e se system s. A lso o f Im portance a re
th e sy n th e s is o f b ic y c lo [4 .2 .2 3 d e c a -2 ,U ,9 -tr ie n -7 ,8 -d io n e (j>6) and study
o f i t s chem istry . F u rth e r in v e s tig a t io n of th e h y d ro ly tic b eh av io r o f
a n ti-8 -ac e to x y b icy c lo [U .2 .2 ]d ec a -2 ,l+ ,9 -tr ie n -7 -o n e (26 ) may p ro v id e in fo r
m ation tow ard sy n th e s is o f £6. Photochem ical rearrangem ents o f d iketone2*636 may produce t r ic y c lo [ 3 .3 .2 .0 ’ ]deca-3> 6-d ien -9 ,10 -d ione , a p o ss ib le
degenera te ketone. A d d itio n a l fu tu re s tu d ie s include re a c tio n o f ketone
1 and d iketone £6 w ith o rganom eta llic re a g e n ts in e f f o r t s t o f u r th e r expand
th e sy n th e tic p o te n t i a l o f th e b ic y c lo [ l |- .2 .2 ] tr ie n y l system .
SUMMARY
T his r e p o r t r e p r e s e n ts th e s tu d y o f t h e s y n th e s is and some o f th e
ch em is try o f b ic y c lo [ l f .2 .2 ]d e c a -2 ,l f ,9 - t r ie n -7 -o n e ( l ) , 8 -k e to b lc y c lo -
[ k . 2 . 2 ]d e c a -2 jfl+,9_t r l e n - 7 - y l c a rb an io n ( 8 ) , carbene (U 2), and carbonium
io n (]■*£). Ketone 1 i s o b ta in e d from r in g expansion o f b icy c lo [l* -.2 .1 ]-
n o n a -2 ,l* ,7 - tr ie n -9 -o n e w ith diazom ethanej sp iro C b ic y c lo [ lf .2 .1 ]n o n a -2 ,4 ,7 "
t r i e n - 9 , 2 1 -o x ira n e ] (2 ) i s a b y -p ro d u c t o f r in g expansion . H ydrogenation
o f !L t o form b ic y c lo [4 .2 .2 jd e c a n -7 -o n e (k) c o n c lu s iv e ly e s ta b l is h e s th e
s t r u c tu r e o f 1 . T reatm ent o f k e to n e 1 w ith deu te rium oxide-sodium d e u te r -
ox ide p ro d u ces a n t l - 8 -d e u te r lob icycloC k . 2 . 2 ]d e c a -2 ,4 , 9 - t r le n -7 -o n e (g^
w hich i s th e n tran sfo rm ed t o 8 ,8 - d id e u te r io b ic y d o [ 4 .2 .2 ] d e c a - 2 ,4 ,9 - t r i e n -
7 -o ne ( l l ) upon lo n g er exposure t o th e d e u te r a t ln g medium.
R e a c tio n o f b ic y c lo [ 4 .2 .2 ] d e c a - 2 ,^ ,9 - t r ie n - 7 - o n e to sy lh y d raz o n e (12)
w ith m e th y llith lu m y ie ld s b ic y c lo [4 .2 ,2 ]d e c a -2 ,4 > 7 > 9 - te tra e n e (l*f) a long
w ith n a p h th a len e and c i s -9 j 1 0 -d ih y d ro n ap h th a len e . Ketone IL form s e n o la te
(3 upon r e a c t io n w ith p o tass iu m t-b u to x id e . E n o la te 8̂ r e a c t s w ith a c e ty l
c h lo r id e t o produce 7 -a c e to x y b ic y c lo [ if .2 .2 ]d e c a -2 ,^ ,7 > 9 - te tra e n e ( lj?) and
w ith t r i m e t h y l s i l y l c h lo r id e t o form 7 - t r jm e th y ls i lo x y b lc y c lo [^ . 2 .2 ]d eca -
2 ,k ,7 j9 - te t r a e n e (2 l ) . E n o la te 8̂ m e th y la te s form ing 7 -m ethoxybi cy c lo
id . 2 . 2 ]deca-2 ,l+ , 7 ,9 - te t r a e n e (17^ Uyfc) and 8 ,8 -d im e th y lb ic y c lo [4 .2 .2 ]d e c a -
2 ,U ,9 - t r ie n -7 -o n e (19, 26%) in glyme. M e th y la tio n o f 8̂ in hexam ethylphos-
phoram ide o r dim ethylform am ide a t 0 ° p roduces 17 (92%). Upon s ta n d in g , 8
77
78
re a r ra n g e s s low ly t o th e an ion o f p - te t r a lo n e and p ro b ab ly th e a n io n o f
e l s - 9> 10- d lh y d ro -2 -n a p h th o lj secondary m e th y la tio n p ro d u c ts a s a conse
quence o f rearrangem en t a re 2-m ethoxy-3 , fr-d ihydronaph thalene ( 2 0 ) and 2-
m ethoxynaphthalene. Ketone 1 r e a c t s v i t h iso p ro p en y l a c e ta te t o form 1£
and w ith p y r ro l id in e t o g iv e 7 -p y r ro lid in o b ic y c lo [ f r .2 . 2 ]d e c a -2 , f r ,7 ,,9 - te t r a e n e
( l 6 ) . 7 - S u b s t l tu te d t e t r a e n e s 15-17 and 21 hydro3yze t o ketone 1_. Methoxy-
t e t r a e n e 3 £ th e rm a lly re a r ra n g e s t o nap h th a len e ( 66$) and 2-methoxynaph-
th a le n e (33$ )•
Lead t e t r a a c e t a t e o x id iz e s k e to n e 1 t o a n t l - 8 -a c e to x y b lc y c lo rfr .2 .2 ld e c a -
2 , h, 9 - t r ien -7 -o n e (26) q u a n t i t a t iv e ly . A t t e s t e d a d d -c a ta ly z e d t r a n s e s t e r -
i f i c a t i o n o f 26 w ith m ethanol form s syn- and a n t i - 8-m ethoxybicyclo[fr.2 . 2] -
d e c a - 2 ,f r ,9 - t r ien -7 -o n e s (28 and 2 9 ) . B icyc lo [fr. 2 . 2 ]d eca-2 ,fr , 9 - t r i e n - 7 ,8-
d io n e monooxlme ( 35 ) r e s u l t s from r e a c t io n o f e n o la te <3v i t h Isoam yl
n i t r i t e in t - b u ta n o l . Ketooxime co n v e rts t o q u in o x a lln e ;5fr w ith o-
pheny lened iam ine. A ttem pts t o p re p a re b ic y c lo [ f r . 2 .2 ]d e c a -2 ,b ,9 - t r i e n - 7 ,8 -
d ione ( 5 6 ) from f a i l e d . R e ac tio n o f (3 v i t h m ethyl fo rm ate p roduces 8 -
fo rn y lb ic y c lo [f r . 2 . 2 ] d e c a - 2 , 9 - t r ie n - 7 - o n e ( 38 ) q u a n t i ta t iv e ly . T reatm ent
o f ;5j3 v i t h h y d raz in e g iv e s 3 >fr“d ia z a t r i c y c lo [ 5. fr.2 . 0a ,S ] t r id e c a - 2 , 5>8 , 10, 12-
p e n ta en e (^9 ) . 7 -D ia z o b ic y c lo [4 .2 .2 ]d e c a -2 ,f r ,9 - tr ie n -8 -o n e (37 ) form s
from r e a c t io n o f ^ v i t h to s y la z id e and t r ie th y la m in e .
D iazoketone 37 c o n v e rts t o bicycloHfr-. 2 . l ln o n a -2 ,4 . 7 - t r l e n -sy n -9 -
c a rb o x y llc a c id (fro) upon p h o to ly s is in d lo x a n e -v a te r . The hom ogeneity o f
foO i s s u b s ta n t ia te d b y fo rm atio n o f m ethy lb icyclo [fr. 2 . 1 ] nona-2 , fr, 7 - t r i e n -
syn-9 -c a rb o x y la te (frl) from r e a c t io n o f fro and diazom ethane. D ecom position •
o f d iazo k e to n e (3j ) v i t h a c e t i c a c id o r hydrogen c h lo r id e p roceeds v ia
7 9
rearrangem ent th rough th e 10-k e to b ic y d o [5 . 2 . 1 ]deca-3 »5>8 - t r i e n - 2- y l c a r -
bonium ion (47) v i th subsequent an ion quenching from th e l e s s e r h indered
s id e o f 4£ to form exo-2-a c e to x y b ic y c lo [g .2 . 1 ]deca-3, g ,8- t r i e n - 10-one (44 )
o r exo- 2-c h lo ro b ic y c lo [ 5 .2 . H d e c a -3 .5 . 8- t r l e n - 10-one (g4 ), r e s p e c tiv e ly .
S i lv e r a c e ta te converts c h lo rid e in to a c e ta te 44. C hloride 54 hydro-
genylyzes t o b ic y c lo [g .2 . 1 ]decan-10-one ( gj>) confirm ing th e s t r u c tu r a l
assignm ent. A ceta te 44 hydrogenates t o form ex o -2 -ace to x y b icy c lo [g .2 .1 ] -
decan-10-one (gO) which upon sa p o n if ic a tio n and o x id a tio n produces b ic y c lo -
[5 .2 .1 ]d ec a -2 ,1 0 -d io n e ( g2 ) . A ceta te 44 and ch lo rid e g4 undergo f a c i l e
Cope rearrangem ents farm ing endo- 6- ( c l s - 2 1-ac e to x y v in y l)- c l s -b lc y c lo [3 .3.0*1-
o c ta -3 , 7-d ie n -2-one (g j ) and endo- 6 - (c i s - 2 * - c h lo ro v in y l) - c is -b ic y c lo [3 • 3 • 0 ] -
o c ta -3*7 -d ien -2 -one ( g8 ) , r e s p e c t iv e ly . A ceta te g7 hydrolyzes t o endo- 6-
(1 ' - o x o e th y l)- c i s - b ic y c lo [3 . 3 . 0 ] o c ta -3f 7-d ie n -2-one (60 ) .
A ttem pted W olff-K ishner re d u c tio n o f ketone 1 , b ic y c lo [4 .2 .2]deca-
2 ,4 ,9 - t r ie n -7 -o n e hydrazone (6^) o r th e sem icarbazone d e r iv a tiv e £ produces
2#3 -d ia z a tr ic y c lo [6 .3 .1 .0 4 , 11]d o d e c a -2 ,g ,9 - tr ie n e (6 4 ). Upon r e a c t io n o f
ketone 1 v i th m ethylhydrazine and po tassium hydroxide, 3- ® e th y l-2 ,3 -d iaza -
t r ic y c lo [ 6 .3 .1 .0 4,X1]d o d e c a - l ,g ,9 - t r ie n e ( j£ ) i s formed. Sodium borohydrlde
re d u c tio n of ke tone 1 y ie ld s b icyc loC 4 .2 .2~1deca-2,4 ,9 - t r l e n -sy n -T -o l ( j j ) .
R eaction o f 77 w ith trip h en y lp h o sp h in e dibrom ide in dimethylformamide p ro
duces b ic y c lo [4 .2 .2 ld e c a -2 ,4 ,9 - t r ie n -sy n -7 - y l form ate (79) . Photochem ical
rearrangem ent o f ketone 1_ under e i t h e r n o n -se n s itiz e d o r s e n s i t iz e d con-2 6d i t io n s lead s t o fo rm ation o f t r i c y c lo [ 3 .3 . 2 .0 * ]deca-3*6 -d ie n -9 (lO )-one
(djj) a s th e m ajor p roduct v i t h t r i c y c l o [ 5. 3 . 0 , 0^ , 10]deca-3i 5- d ien -8 -one
(84) t e n t a t i v e ly a ssig n ed a s th e minor p ro d u c t. Ketone 8j^ r e v e r ts t o
ketone 1 upon trea tm e n t v i t h a c id .
EXPERIMENTAL
M elting P o in ts . M elting p o in ts v e re determ ined u s in g a Thomas Hoover
c a p i l la ry p o in t ap p ara tu s and a re u n co rrec ted .
E lem ental A nalysis. E lem ental a n a ly se s v e re perform ed by Chem alytics, I n c . ,
Tempe, A rizona; M ic ro an a ly sis , I n c . , V ilm ington, Delaware; o r G a lb ra ith
L a b o ra to r ie s , I n c . , K noxville , Tennessee.
U l t r a v io le t S pec tra . U l t r a v io le t .s p e c t r a vere ob ta ined u sin g a Cary Model
lU re c o rd in g spectrophotom eter.
In f ra re d S p ec tra . In f ra re d s p e c tra v e re ob tained on P e rk in Elmer Model
137 o r 1*57 reco rd ing spectropho tom eters. A ll sp e c tra v e re c a l ib ra te d v i th
a p o ly s ty ren e ab so rp tio n peak a t 1601 cm"1.
Nuclear Magnetic Resonance S p e c tra . N uclear m agnetic resonance s p e c tra
v e re determ ined u sin g V arian A sso c ia te s nuclear m agnetic resonance sp e c tro
photom eters Models A-60, A-60A, and HA-100. Unless noted o therw ise , a l l
s p e c tra v e re measured in chloroform -d o r carbon te t r a c h lo r id e so lu tio n s
u s in g te tra m e th y ls i la n e a s an in te r n a l s tandard .
Gas Chromatography. Gas chromatography vas perform ed u sin g a W ilkins
Aerograph Model A-90-C v i th a therm al co n d u c tiv ity d e te c to r . Column A was
composed o f 20$ SEr30 on Chromosorb W (0 .25" x 1 2 ') . Column B c o n s is te d
o f 15$ Carbovax 20M on Chromosorb W (0 .25" x 10* )* Column C vas made o f 12$
81
Apiezon J on Chromosorb P (0 ,125" x 1 0 ') . R e la tiv e peak a re as v e re ob tained
by m u ltip ly in g peak h e ig h t by peak v id th a t h a l f h e ig h t.
P re p a ra tio n o f B icy c lo [U .2 .1*)nona-2, **, 7- t r le n -9 -o ne. U nsnturated ketonese
vas p repared acco rd ing t o th e method o f T. A. Antkowiak in k9-6$% o v e ra l l
y ie ld from c y c lo o c ta te tra e n e . Glc a n a ly s is (column A) shoved th e p roduct
t o be 99+^ pure; i r (n e a t) : 1800 cm"1 ( s ) j nmr: 6 5 .9 (n , 6h, H a t C-2,
-5 , - 5 t - 7 , - 8 ) ancL 3 .1 (m, 2H, H a t C - l , - 6 ) .
R eaction o f BicycloL**, 2 . l]n o n a-2 , k, 7 - tr ie n -9 -o n e v i th Diazomethane.
A lcoholic e th e re a l diazomethane (600 ml o f O.33 M so lu tio n , 0 .2 mole) vas
p repared by charg ing a f la s k c o n ta in in g a s o lu tio n of potassium hydroxide
(120 g) in m ethanol (300 .ml) - v a te r (80 ml) and e th e r (600 ml) v i th b i s -
(N -m ethy l-N -n itro so )te reph thalim ide (70$ suspension in m ineral o i l ) a t 0°.
T h e .f la sk vas equipped v i th non-ground g la s s ta k e o f f and a tta c h e d t o a
re c e iv e r cooled in iso p ro p an o l/d ry ic e . The m ix ture vas gen tly vanned
and d i s t i l l a t i o n continued u n t i l th e d i s t i l l a t e no longer vas y e llo v .
The diazomethane s o lu tio n vas added a l l a t once t o a so lu tio n o f ketone
(10.5 Bt 0 .°7 9 mole) in chloroform (80 ml) - m ethanol (1*0 ml) con ta in ing
l ith iu m c h lo rid e (0 .1 g, 0.002** mole) a t 0 ° . The m ixture vas s to re d a t 0°
u n t i l s t a r t in g ketone d isappeared (c a 3 h r ) a s evidenced by m icro t i c
a n a ly s is on s i l i c a g e l G u s in g e ther-hexane (2 :3 ) as e lu a n t. Formic a c id
(6 ml, O.15 mole) vas c a re fu l ly added d r op w ise (5 min) v i th s t i r r i n g and
th e m ixture e x tra c te d v i th v a te r - e th e r . The aqueous la y e r vas vashed w ith
e th e r ( 2x) and th e combined e th e r la y e rs vashed v i th s a tu ra te d sodium
b ica rb o n a te so lu tio n ( 2x ), s a tu ra te d b r in e s o lu tio n ( l x ) , and f i l t e r e d
through D r ie r i te . A fte r co n ce n tra tio n o f th e e x tr a c t under reduced p re s su re ,
82
th e o i ly re s id u e was d i s t i l l e d t o y ie ld a w ater w h ite m ix ture ( l l .5 g> 909&)
o f b icyc lo [l+ .2 . 2 ]deea-2 ,l+,9 - t r i e n - 7-one ( l ) and sp iro [b icy c lo [l+ ,2 . 1}nona-
2 ,l+ ,7 - tr ie n -9 ,2 f-o x iran e ] (2 ) , bp l+3-l+7° (0 .15 mm),' mass spectrum m/e =
11+6.
A nal. Calcd f o r C10H10O: C, 02.16; H, 6 . 89 .
Found: C, 81 .70; H, 6 .7 2 .
S ep a ra tio n , a n a ly s is , and i s o la t io n o f th e p roducts by g lc (column A)
gave epoxide 12 ( r e l a t i v e r e te n t io n tim e = 1 . 0 , 15- 50?6) and ketone 1 ( r e l a
t iv e r e te n t io n tim e «= 1 . 2 , 85- 5096) .
D ata fo r epoxide 2: i r (n e a t) : 980 (m), 860 ( s ) , and 7*+5 cm"1 ( s ) j
nmr: 6 6 .1 (m, 1+H, H a t C-2, -3 , -*+, - 5 ) , 5*55 (d , 2H, H a t C-7, - 8 ) , 3 .0
( s , 2H, H a t C -2 ') , and 2 .7 5 (m, 2H, H a t C -l, - 6 ) . Exact mass; ca lcd
11+6.0732; found 11*6.073^.
A nal. Calcd f o r C10H10O: C, 82 .16; H, 6 . 89 .
Found: C, 81.99; H, 6 . 88 .
Data fo r ketone 1: i r (n e a t) : 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 a t C - l) ,Eft 0H
and 2 .55 (d w ith s , 2H, H a t C-8 ) ; uv: 202, 258, 265, and 300 nm
(®max “ ^ ^ 0 , 3070, 2920, and 373). Exact mass: ca lcd 11+6.0732; found
11+6.073^.
A nal. Calcd for C3.0H10O: C, 82 .16 ; H, 6 . 89 .
Found: C, 82 .20 ; H, 6 . 83 .
R eaction of B icy c lo [l+ .2 .2 ]d eca-2 ,l+ ,9 -trien -7 -o n e ( l ) w ith Sem icarbazide 28
H ydrochloride. The crude re a c tio n m ix ture o f r in g expansion of
bicycloLl+.2 . 1 ]nona-2 ,l+,7- t r i e n - 9-one co n ta in in g ketone 1 (8596) and epoxide
J2 (15$) (3 .15 Et O.OI85 mole) was d isso lv ed in e th a n o l (250 m l)-w ater (20
m l). Sem icarbazide hyd ro ch lo rid e (5 g) and sodium a c e ta te (7*5 g) vere
added and th e m ix ture warmed f o r 1 h r a t 75 • The m ixture was concen tra ted
under reduced p re s su re t o h a l f volume and cooled in ic e . The crude semi-
carbazone (3*29 Bt 88$ based on ketone) vas f i l t e r e d and a i r d r ie d . Pure
b icy c lo [l* .2 . 2 ]d eca-2 ,l* ,9 - t r i e n - 7 -one semicarbazone (£) was ob ta in ed as w h ite
c r y s ta l s , mp 199. 5- 2OO.50 by r e c r y s t a l l i z a t i o n from 50$ aqueous e thano l
and c l a r i f i c a t i o n w ith N o rite . Exact mass: ca lcd 203.1059; found 203.1061.
A nal. Calcd f o r C11NX3N3O: C, 65.00; H, 6.1*5*
Pound: C, 61*. 68; H, 6.1*3.
P re p a ra tiv e I s o la t io n o f B iey e lo [l* .2 .2 ]d eca -2 ,l* ,9 -trien -7 -o n e ( l ) . Two
methods o f I s o la t io n o f 1 were developed; method I i s su p e r io r and vas
used e x te n s iv e ly f o r th e rem ainder o f t h i s work.
Method I . The crude o i ly re s id u e i n i t i a l l y ob ta ined a f t e r r in g
expansion w ith diazom ethane was re f lu x e d w ith G ira rd 's re a g e n t T (ll*.0 g,
0 .08 mole) f a r 1 h r in a c e t ic a c id (10 m l), e th a n o l (60 m l), and w ater (1*
m l). The m ix ture v as cooled to 25° and d i lu te d w ith w ater, b r in e , and
e th e r . A f te r th e e th e r la y e r had been sep a ra ted , th e aqueous la y e r was
warmed w ith co n cen tra ted h y d ro ch lo ric ac id (20 ml) t o 75° f o r 15 min. The
aqueous m ix ture v a s cooled, e x tra c te d w ith e th e r , and th e n re h e a te d . T his
procedure vas re p e a te d s e v e ra l tim es and th e e th e r e a l e x tr a c ts v e re com
b ined , washed w ith aqueous sodium b ica rb o n a te ( 2x ) , b r in e ( l x ) , f i l t e r e d
th rough D r ie r i t e , and co n cen tra ted under reduced p re s su re . D is t i l l a t io n o f
th e re s id u e y ie ld e d 1 as an o i ly w h ite s o l id ( 5.75 gi 50$ ) , bp 71-73° (0 .1
mm). Glc a n a ly s is o f th e p roduct (column A) showed no rem ain ing epoxide 2 .
8U
Method I I . Crude sem icarbazone 2. (3*00 g , 0 ,015 mole) was d is so lv e d in
p y ru v ic a c id ( l 6 g) and s t i r r e d f o r 30 h r tinder argon . The r e a c t io n m ix ture
was d i lu te d w ith w a te r (60 m l), n e u tra l iz e d w ith aqueous sodium b ic a rb o n a te
and e x tra c te d w ith e th e r . The e th e r la y e r was washed w ith b r in e ( l x ) ,
f i l t e r e d th ro u g h D r ie r i t e , and c o n c e n tra te d under reduced p re s s u re . Pure
ketone 1 was o b ta in ed by d i s t i l l a t i o n , bp 83- 86° (0 .2 mm), (O.JO g , 23?G);
t h i s compound matched in a l l ways !L a s p rep a red v ia method I .
R eac tio n o f B ic y c lo [h .2 .2 ]d e c a -2 ,U ,9 - tr ie n -7 -o n e ( l ) w ith 2 ,l+ -D in itropheny l- 28
hy d ra z in e . Ketone 1 (0 .2 1 g, 0.0011+ mole) d is so lv e d in ch loroform (10
ml) was mixed w ith 2 ,4 -d ln itro p h e n y lh y d ra z in e (0 . 1+ g) d is so lv e d in concen
t r a t e d s u l f u r i c a c id (2 m l), w a ter (3 m l), and m ethanol (10 m l), and s t i r r e d
f o r 1 h r a t 25°. The crude p ro d u ct was f i l t e r e d and a i r d r ie d (0 .3 g, 6k%).
Pure b ic y c lo [l+ .2 ,2 ]d e c a -2 ,l+ ,9 - tr ie n -7 -o n e 2 ,l+ -d in itropheny lhydrazone was
o b ta in ed as b r ig h t orange n e e d le s , mp 221- 222 . 5° , from 1:1 m ethanol-
chloroform ; mass spectrum m/e = 326; i r (KBr): 1630 (m), 1330 (m ), and
1510 cm"1 (m).
A nal. C alcd f o r C ieH nl^O *: C, 58.89; H, 4 .32 ; N, 17 .17 .
Found: C, 58.64; H, 4 .20 ; N, 17.20.
R eac tion o f B ic y c lo L 4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e ( l ) w ith Hydroxylamlne 28
H ydroch lo ride . Ketone 1 ( l .O g, O.OO69 m ole) and hydroxylam lne hydro
c h lo r id e (1 .3 9 8* 0 .020 mole) were d is so lv e d in m ethanol (20 m l). P o tassium
carbonate ( 1 .3 9 8/ 0 .010 mole) in w a te r (10 m l) was added and th e m ixture
was s t i r r e d f o r 18 h r a t 25°. W ater (75 ml) was added and th e m ix tu re was *
e x tra c te d w ith e th e r (3 x ). The e th e r la y e r was washed w ith b r in e , f i l t e r e d
th rough D r ie r i te and co n cen tra ted under reduced p re ssu re t o produce a yellow
o i l (1 .0 g , 91$). The o i l was c ry s ta l l iz e d by so lu tio n In e th e r (8 ml) -
hexane ( l 6 ml) and s to rag e a t -20°. Pure b ic y c lo [^ .2 .2]deca-2,1+, 9 - tr ie n -T -
one oxime was ob tained as w h ite c r y s ta l s , 115 131- 132° , mass spectrum m/e a
l 6l | i r (KBr p e l l e t ) : 3300 ( s ) and 1660 cm"1 (v ) j nmr: 6 5 .8 (m, 6h , H a t
C-2, -3 , -It, -3 , -9 , -1 0 ) , 3 .9 (dd, IB, H a t C-6 ) , 3*0 (m, IB, H a t C - l) ,
and 2 .6 (m, 2H, H a t C-8 ) .
A nal. Calcd fo r CibHnNO: C, 7 k . 51} H, 6 . 88 ; N, 8 . 69 .
Found: C, 7 ^ .3 0 ; H, 7*05; N, 8 .5 k .
C a ta ly t ic H ydrogenation o f B icyclo [lt. 2 .2 ]d ec a -2 ,4 ,9 - tr le n -7 -o n e ( l ) . A
m ix ture o f ketone 1 ( 2.00 g, O.OI36 mole) and 5% pallad ium on carbon (0 .2 g)
in e th a n o l (150 ml) was p lac ed in a P a r r hydrogenator; in 30 min uptake
o f hydrogen was com plete. The re a c t io n m ixture was f i l t e r e d and concen
t r a t e d under reduced p re s su re ; th e re s id u e was d isso lv e d in e th e r . The
e th e r e a l s o lu tio n was washed w ith b r in e , f i l t e r e d through D r ie r i te , and
re c o n c e n tra te d tinder reduced p re s su re . The r e s u l ta n t b ic y c lo t^ .2 .2 ]d e c a n -
7-one, (4p 1 .97 8t 95$)* was p u r i f ie d by sub lim ation and c r y s ta l l i z a t io n from
pentane to produce w hite c r y s ta l s , mp 155-157°* Glc a n a ly s is (column A)
showed th e p roduct t o be one component; i r (KBr p e l l e t ) : 1720 cm"1; nmr:
6 2 .3 (d oub le t imposed on m, IfH, H a t C - l , - 6 , - 8 ) , and 1 .7 (m, 12H, H a t0
C-2, -3 , -U, -5 , -9 , -1 0 ). Exact mass: ca lcd 132.1201; found 132.1201;.
23R eaction o f B icyclo[U .2 .2]decan-7-one (k ) w ith 2 ,U -D ln itropheny lhydrazlne .
S a tu ra te d ketone 4 (0 .3 g , 0.0033 mole) was re a c te d w ith excess 2 , l ; - d ln i t r o -
phenylhydrazine in e th a n o l w ith s u l f u r ic a c id c a ta ly s t a s p re v io u s ly des
c rib e d . The crude orange product (0 .6 0 g, 35$) on r e c r y s t a l l i z a t i o n from
86
e th a n o l produced pu re b icy c lo [4 .2 .2 ]d e ca n -7 -o n e 2 ,4 -d in itropheny lhyd razone ,
mp 179.5-181°, mass spectrum m/e = 332) i r (KBr): 1650 ( s ) , lM)0 (m),
1350 ( s ) , 1080 (m), 9^0 (m), and 830 cm"1 (m).
A nal. Calcd f o r C16H20N4O4 : C, 57.82) H, 6 .06) N, 16.86.
Found: C, 57.79) H, 5.96) N, 16 .57 .
28R eaction of B lcy c lo [^ .2 .2 ]d ecan -7 -o n e (ji) y l th Sem icarbazide H ydrochloride.
S a tu ra te d ketone U, (0 ,70 g, 0.001)6 mole) in e th a n o l (12 ml) - v a te r (4 ml)
vas mixed v i th sem icarbazide hyd roch lo ride ( l g) and sodium a c e ta te (1 .5 g ) ,
varmed t o 75° and d i lu te d v i t h v a te r (50 m l). A fter coo ling th e m ixture t oft O / ®0 °, th e crude p ro d u ct vas f i l t e r e d and a i r d r ie d , mp 208-210 ( l i t mp 205-
207°) (O.57 g, 60$ ) . R e c ry s ta l l iz a t io n from 50^ aqueous e th a n o l produced
pure b icyc loL 4 .2 .2 ]decan -7 -one sem lcarbazone (jj) as v h i te c r y s ta l s , mp 220-
222°) i r (KBr): 3700 ( s ) , 3400 (e)> and 1710 cm"1 ( s ) . Exact mass: ca lcd
209.1528) found 209.1531.
A nal. Calcd f o r C11H19N3O: C, 63.13) H, 9 .15) N, 20 .08 .
Found: C, 62.99) H, 9 .19) N, 20.32.
C a ta ly t ic Hydrogenation of B ic y c lo [4 .2 .1 ]n o n a -2 ,4 ,7 - tr ie n -9 -o n e . U nsatura-
te d ketone ( l . l 6 g , 0.00879 mole) in e th a n o l (100 ml) v i th 5% Pd on carbon
(0 .05 g) vas hydrogenated in a F a r r ap p ara tu s u n t i l t h e o r e t i c a l hydrogen
uptake (2 h r). Workup as b efore produced I .03 g o f crude product (85$ ).
Sub lim ation o f th e m a te r ia l v i t h subsequent c r y s ta l l i z a t io n frcm pentane
produced pure b icy c lo [4 .2 .1 ]n o n an -9 -o n e (6) as v h i te c r y s ta l s , mp 98-101? s&
( l i t mp 109- m 0 ). Glc an a ly sis (column A) shoved th e product as one29
component) ir (KBr) p e l le t : 1740 cm" 1 ( l i t 1737 cm"1)) nmr: 6 1.55 (®
* superimposed on m). Exact mass: ca lcd 138.101)6) found 138.1045*
R eaction o f B icydo[U .2 .1 ]nonan-9-one (6 ) w ith Diazomethane. A lcoholic
e th e r e a l diazomethane (50 o l , 0.33 Mj 0,015 mole) as p rev io u s ly p repared
vas added a t 0 ° to s a tu ra te d ketone 6 (0 .5 g, O.OO36 mole) d isso lv e d in
e th e r (6 ml) - m ethanol ( l m l). A fte r 5 days form ic a c id vas added and th e
m ix ture vas vashed v i th aqueous sodium b ica rb o n a te and b r in e , and f i l t e r e d
th rough D r le r l t e . A nalysis o f th e re a c tio n m ixture by g lc (column A)
shoved s t a r t i n g ketone 6 ( r e l a t iv e r e te n t io n tim e » 1 . 0 , r e l a t iv e a re a «
10 .0 ) and b ic y c lo [^ .2 . 2 ]decan-7-one (jj^ r e l a t i v e r e te n t io n tim e = 1 . 75 ,
r e l a t i v e a re a = 1 .0 ) . The p roduct ketone ^ vas is o la te d by p re p a ra tiv e
g lc and p o ssesse s th e same s p e c t r a l p ro p e r t ie s a s th e compound p repared
by c a ta ly t i c hydrogenation of b ic y c lo [^ .2 . 2 ]d eca-2 , ^ , 9 - t r i e n - 7-one ( l ) .
B ase-C atalyzed Mono- and D ld e u te ra tlo n of B lcyclo[U . 2 .2 ]deca-2 , k, 9 - t r le n - 7 -
one ( l ) . Ketone 1 ( 5 0 mg) vas d isso lv e d in carbon te t r a c h lo r id e (0 .5 ml)
c o n ta in in g Vf> TM3, and deuterium oxide (3 d rops) con ta in ing sodium hydride
(57$ suspension in m inera l o i l , 5 g ra in s ) vas added. The re a c tio n v as run
in an nmr tube and mixed by c o n tin u a l tum bling a t 25° j r e a c t io n p rog ress
vas m onitored by nmr a n a ly s is examining th e ab so rp tio n a t 6 2 .55 f o r peak
and in te g ra t io n d isappearance . A fte r 12 h r , h a l f o f th e o rganic phase vas
removed, d r ie d v i th anhydrous potassium carb o n ate , and concen tra ted under
reduced p re s su re t o p rov ide a n ti-8 -d e u te r io b ic y c lo [^ .2 .2 ]d e c a -2 ,U ,9 - tr ie n -
7 -one (& 25 mg)> nmr: a 5 .9 (m, 6h, H a t C-2, -3 , -»+, -5 , -9 , -1 0 ) , 3 .5
(m, IB, H a t C -6), 3 .0 (m, 1H, H a t C - l) , and 2 .55 (a , H a t C -0).
E xact mass: c a lcd l>f7.079^f found lV f.0791.
The rem aining o rgan ic la y e r vas tumbled c o n tin u a lly a t 25° -an ad d i
t i o n a l 8 .5 days u n t i l complete d isappearance o f th e m ethylene a b so rp tio n
v as observed . The aqueous la y e r vas removed; th e o rg a n ic la y e r v a s worked
up as above t o y ie ld 8 , 8 -d id e u te r io b ic y c lo £ 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 a t 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) .
R eac tio n o f B ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e ( l ) w ith P o tassiu m t -
B utoxide and D euterium Oxide. Ketone IL ( l .O g , O.OO685 mole) was added t o
a s o lu t io n o f p o tass iu m t -b u to x id e (2 .5 0 g , 0.022 m ole) in d ry hexam ethyl-
phosphoram ide (50 ml) a t 0 -5 ° and s t i r r e d f o r 4 min. D euterium oxide
(5 ml) was added and s t i r r i n g co n tin u ed f o r an a d d i t io n a l If m in. Boron
t r i f l u o r i d e e th e r a te was th e n slow ly added u n t i l t h e r e a c t io n m ix tu re was
s l i g h t l y a c id ic . W ater (100 m l) was added and th e m ix tu re was e x tra c te d
w ith e th e r (If x 50 m i). The e th e r la y e r was washed w ith w a te r (3x) and
s a tu r a te d b r in e . F i l t r a t i o n th ro u g h D r i e r i t e , c o n c e n tra tio n under reduced
p re s s u re , and d i s t i l l a t i o n y ie ld e d 8 ,8 -d id e u te r io b ic y c lo [U .2 .2 ]d e c a -2 ,4 ,9 -
t r ie n - 7 - o n e (rL , O.75 g , 75%), bp 72-76° ( 0 .1 mm). The p ro d u c t, on th e
b a s i s o f i t s nmr, i r , and g lc a n a ly s i s , v as i d e n t i c a l t o th e p re v io u s ly
p rep a red k e to n e .
R eac tio n o f B ic y c lo [ lf .2 .2 ]d e c a -2 ,J f ,9 - tr ie n -7 -o n e (jl) w ith P o tassiu m t -
B utoxide and W ater in D im ethylform am ide. Ketone 1 (0 .1 5 g, 0 .0 0 1 mole)
c o n ta in in g nap h th a len e ( 0 .13 g , 0 .0 0 1 mole) as an i n te r n a l s ta n d a rd was
d is s o lv e d in d ry dim ethylform am ide (5 m l) and added t o a s o lu t io n o f p o ta s
sium t-b u to x id e ( 0 .2 2 g , 0 .002 mole) in dim ethylform am ide (5 m l) a t 0° and
th e m ix tu re was s t i r r e d f o r 0 .5 h r . The r e a c t io n m ix tu re v as poured in to• *
w ate r (50 m l) and n e u tr a l iz e d w ith 3N h y d ro c h lo r ic a c id . The aqueous m ix tu re
v as e x tr a c te d w ith e th e r (3x ) ; th e comb in e d o rg an ic e x t r a c t v a s washed w ith
w ater (3 x ), aqueous sodium b ic a rb o n a te , and s a tu ra te d b r in e . F i l t r a t i o n
th rough D r ie r i t e and co n ce n tra tio n under reduced p re s su re y ie ld e d 0 .2 5 S
(92^ ) o f a m ixture composed o f s ta r t in g k e t o n e l and naphthalene by g lo
a n a ly s is (column A). Nmr in te g r a l a n a ly s is o f th e p roduct m ix ture showed
th e r a t i o o f n aph tha lene:ke tone to be 1 . 0 ; 0 . 92 .
R eaction o f B ic y c lo [4 .2 .2 ]d e c a -2 ,lf ,9 - tr ie n -7 -o n e ( l ) w ith T osylhydrazide.
Ketone 1 (l.OO g, O.OO69 mole) in e th a n o l (25 ml) waB mixed w ith a s o lu t io n
o f to sy lh y d raz id e ( 1 .60 g, 0.0100 mole) i n e th a n o l (25 ml) co n ta in in g con
c e n tra te d h y d ro ch lo ric ac id ( l drop) f o r 5 h r a t 25°. The s o lu t io n was
reduced t o h a l f volume under reduced p re s su re and coo led to -2 0 ° . The p ro
duct was f i l t e r e d and th e f i l t r a t e vas co n cen tra ted ; th e t o t a l y ie ld o f
d e r iv a tiv e was 1 .66 g (77^). R e c ry s ta l l iz a t io n from e th a n o l produced
b ic y c lo [U .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e to sy lhydrazone ( 12 ) aB w hite c ry s ta l s ,
mp 156- 156° , masB spectrum m/e « $lkf i r (KBr p e l l e t ) : 3^50 (w), 3250 (m),
2950 (m), 16U0 (m), and U 90 cm"1 ( s ) ; nmr: 5 7 .52 (broad s , 1H, N-H),
7 .52 (AB, a rom atic C-H), 5*9 (m, 6h, H a t C-2, -3 , -If, -5 , -9 , -1 0 ) ,
3 .5 (q u in te t , 1H, H a t 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, m ethyl C-&).
A nal. Calcd f o r Ci7HieN2Q2S: C, 6I+.9U; H, 5 .77; N, 8 .91 .
Found: C, 6If.8If; H, 5-7^; N, 8 .73 .
R eaction o f B ic y c lo [4 .2 .2 ]d e c a -2 ,lf ,9 - tr ie n -7 -o n e ( l ) w ith B enzenesu lfo ry l-
hydraz lde . Ketone JL (l.lfO g, 0.0105 mole) in e th a n o l (50 ml) was combined
w ith benzenesu lfonylhydrazide (2.3*f g , O.OI36 mole) i n e th an o l (50 ml)
co n ta in in g co n cen tra ted h y d ro ch lo ric ac id ( l drop) and th e m ix ture vas
s t i r r e d overn igh t a t 25°. Subsequent rem oval o f th e so lv en t under reduced
90
p re s su re , d is so lu tio n o f th e re s id u e in m ethylene ch lo rid e (20 ml) - hexane
(20 m l) and s to rage a t - 20° p rov ided v h i te c ry s ta l s o f b ic y c lo [4 . 2 . 2 ]deca-«
2 ,4 ,9 - tr ie n -7 -o n e benzenesulfonylhydrazone ( ] 2 .7 0 g, 85^ ) , up 62- 65°}
i r (KBr p e l l e t ) : 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 a rom atic C-H), 5 .70 (m, 6h , H a t C-2, -3 , -If, - 5, -9 , -1 0 ), 3 .5
(q u in te t , 1H, H a t C-6 ) , 2 .9 (m, Ifl, H a t C - l) , and 2 .5 (m, 2H, H a t C-8 ) .
A nal. Calcd f o r CieHieNaOgS: N, 9*52.
Found: N, 9*05.
R eaction o f B ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e Tosylhydrazone (12 ) w ith3 3
M ethylllthivtm . Tosylhydrazone 12 (200 mg, 0 .6 4 mmol) v as suspended in
hexane (5 nil) and th e system vas f lu sh e d v l t h argon a t 0° . M ethyllith ium
(2 .0 ml, 1 .45 Mj 2 .9 mmol) vas added slow ly , th e system vas warmed t o 25°,
and th e r e a c t io n m ix ture vas s t i r r e d 3 h r . W ater (3 ml) v a s added drop-
v is e , th e la y e rs were se p a ra te d , and th e w ater la y e r vas vashed w ith e th e r
(2x ). The combined o rg an ic la y e r s v e re vashed w ith b r in e , f i l t e r e d
th rough D r ie r i te , and c a re fu l ly co n cen tra ted under reduced p re s su re . The
re s id u e (72 mg, 84%) c o n s is te d o f f iv e components (g lc a n a ly s is , column A);
th e th r e e major components (98$ o f th e m ix tu re) v e re id e n t i f ie d a s jc is -9 , 10-
dihydronaphthalene ( r e l a t i v e r e te n t io n tim e » 1 . 0 , r e l a t i v e a re a » 1 . 0 ) ,*
b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,7 ,9 - te tra e n e (14, r e l a t i v e r e te n t io n tim e = 1 .14 ,
r e l a t i v e a re a <= 66) , and naphthalene ( r e l a t iv e r e te n t io n tim e = 1 . 50, r e l a
t i v e a re a = 3*6). P re p a ra tiv e g lc (column A) p rov ided p u re samples o f each
compound} re te n tio n tim es and s p e c t r a l p ro p e r t ie s o f each compound matched
9134
th o se of a u th e n tic sam ples; nmr of lk : 6 5 .8 (m, 8H, H a t C-2, -3 , -1+,
-5# - I t S t - 9 f -10)> ana 3 .15 (m, 2H, H a t C -l, - 6 ).
R eaction o f B icy c lo [U .2 .2 ]d eca-2 ,U ,9 -trien -7 -o n e ( l ) w ith Isopropenyl
A ceta te . Ketone 1 (0 .50 g, O.OO3I+ mole) was d isso lv e d in isop ropeny l ace
t a t e (13 ml) c o n ta in in g a t r a c e o f £ - to lu e n e su lfo n ic ac id and th e m ixture
was re f lu x e d f o r 60 h r . Potassium carbonate was added, th e excess so lv en t
was removed under reduced p re s s u re , and th e crude re s id u e was d i s t i l l e d ,
bp 78-79° (0»05 mm). The d i s t i l l a t e (O.55 St 86^ ) con ta ined only one peak
as evidenced by g lc a n a ly s is (column A); p re p a ra tiv e g lc was used t o p u r ify
th e 7 -a c e to x y b ic y c lo [4 .2 .2 ]d e c a -2 ,h ,7 >9 - te tr a e n e (15 ); i r (n e a t) : 1760
( b ) and 1210 cm- 1 ( s ) ; nmr: • 6 3*85 (m, 7H, H a t 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).
A nal, b a led fo r CigH^O^: C, 76.57; H, 6 .^3 .
Found: C, 76.62; H, 6 .35-
R eaction o f B lc y c lo [fr .2 .2 ]d e c a -2 ,k ,9 - tr ie n -7 -o n e ( l ) w ith Potassium t -
Butoxide and A cety l C h loride in Glyme. Ketone 1 (0 .10 g, 0.0007 mole) was— n r r n n m i~n~if~ i~ i i~ t~\ Of i~ i~n~ t~~ 1—1 < ~ i 1— 1— 1 —1~ r
d isso lv e d in d ry glyme (3 ml) a t 25°. PotasBium t-b u to x id e (0 ,22 g, 0.002
mole) vas added a l l a t once and th e r e s u l t in g brown s lu r ry vas s t i r r e d
ra p id ly f o r lf-5 min. A cety l ch lo rid e ( 0 . l6 ml, 0 .002 mole) vas added and
s t i r r i n g o f th e m ix ture vas continued f o r 5 min. Potassium carbonate
(0 .2 g) vas added, th e so lv en t vas removed under reduced p re s su re , and th e
re s id u e v as d isso lv e d in e th e r (15 m l). The e th e re a l la y e r v a s f i l t e r e d
t o remove suspended s o l id and co n cen tra ted under reduced p re s su re . Glc
a n a ly s is (column A) o f th e yellow o i ly re s id u e (0 .1 2 g) rev e a le d a th re e
92
component mixture* u n id e n tif ie d im purity ( r e l a t i v e r e te n t io n tim e *= 1 . 0 ,
r e l a t i v e a re a Jf b 9 ) , s t a r t i n g ketone 1 ( r e l a t iv e r e te n t io n tim e «= 1 . 6 ,
r e l a t i v e a re a $ ** 8 ) , and 7 -a c e t oxybicyclo[h . 2 . 2 ]deca-2 , k , 7 , 9 - te t r a e n e ( l ^
r e l a t i v e r e te n t io n tim e «= 2 .2 , r e l a t i v e a re a % = 83) . P re p a ra tiv e g lc p ro
vided pure sam ples o f th e p roducts vhose s p e c t r a l p ro p e r t ie s matched th o se
o f a u th e n tic sam ples.
R eac tion of 7 -A cetoxyblcyclo[fr.2 .2 ]d e c a -2 ,lf ,7 j9 - te tra e n e ( l j j ) w ith 3N
H ydrochloric A cid. A cetoxy tetraene 15 (0 .20 g , 0.0011 mole) vas d isso lv e d
In hexamethylphosphoramlde (3 m l); h y d ro ch lo ric a c id (3N) vas added and th e
s o lu t io n vas s t i r r e d o v ern ig h t a t 25°. The r e a c t io n m ixture vas poured
in to w ater (30 ml) and the. r e s u l ta n t suspension e x tra c te d w ith e th e r ( 3x ) .
The conibined e th e r la y e rs v e re vashed w ith w a te r (3 x ), aqueous sodium ■bi
carbonate , and s a tu ra te d b r in e . F i l t r a t i o n th rough B r ie r i te and concen
t r a t i o n wider reduced p re s su re y ie ld e d an o i l ( 0 . l 6 g) which was shown to
be a 1:19 m ix ture o f s t a r t i n g a c e ta te 1^ and b icy c lo [U ,2 . 2]d ec a -2,U ,9-
t r ie n -7 -o n e ( l ) by nmr and g lc (column A) a n a ly s is .
R eaction o f B ic y c lo [h .2 .2 ]d e c a -2 ,l ; ,9 - tr ie n -7 -o n e ( l ) w ith P y rro lid in e .
Ketone 1 (0 .16 g , 0.0011 mole) and p y r ro l id in e (0 .16 g, 0.0022 mole) were
d isso lv e d in d ry benzene (10 ml) co n ta in in g s e v e ra l g ra in s o f ^ to l u e n e -
su lfo n ic a c id . The re a c t io n m ixture was re f lu x e d f o r 12 h r making use o f a
Dean S ta rk w ater se p a ra to r . The dark red-brow n s o lu t io n vas concen tra ted
in vacuo to produce a dark brown re s id u e (0 .2 2 g ) . A fte r s to ra g e under
reduced p re ssu re fo r s e v e ra l hours, th e h ig h ly w ater s e n s i t iv e p roduct was
t r a n s fe r r e d t o an nmr tu b e in carbon te t r a c h lo r id e under argon. Nmr a n a ly s is
93
showed t h a t T -p y rro lid in c fb ic y c lo p . 2 .2 ]d ec a -2 ,h ,7 , 9 - te tr a e n e ( l 6, ca 9036)
had formed} s t a r t in g ketone and benzene v e re th e im puritie s} nmr; 6 5*9
(m, 6h , H a t C-2, -3 , -4 , -5# -9# -1 0 ) , 4 .1 5 (dd, 1H, H a t C-8 ) , 3 .4 (m,
2H, H a t C -l, - 6 ) , 3-0 (m, 4H, -H-CH2-C ), and I .85 (m, 4h, -N-C-CH2 - ) .t
The s e n s i t iv i t y o f th e p roduct 16 p rec luded i r or conibustion analysis}
upon stand ing in a nmr tu b e fo r one day complete h y d ro ly s is o f th e enamine
t o th e s t a r t i n g ketone jL and p y r ro lid in e had occurred . Exact mass:
c a lcd 199.1361} found 199.1359.
R eaction o f T -P y rro lld ln 6 b lc y c lo [4 .2 .2 ]d ec a -2 ,4 ,7 ,9 - te t r a e n e ( l ^ ) w ith
3N H ydrochloric Acid. Enamine 16 d isso lv e d in carbon te t r a c h lo r id e con-
ta ln ln g 1$ TMS vas sw irled w ith h y d ro ch lo ric ac id (3N, 3 d rops) f o r 15 tain
a t 25°. The aqueous la y e r was removed and th e o rg an ic la y e r d r ie d over
anhydrous po tassium carbonate . The s o lu tio n on a n a ly s is by nmr and g lc
(column A) was found to c o n ta in b ic y c lo [4 .2 .2 jd e c a -2 ,4 ,9 - tr ie n -7 -o n e ( l )
e x c lu s iv e ly .
R eaction o f B icyclo [ 4 .2 .2 ]d eca-2 ,4 ,9 - tr ie n -7 -o n e ( l ) w ith Potassium t-^
Butoxide and Methy l F lu o ro su lfo n a te in Hexamethylphosphoramide. Ketone 1
(O .5O g, 0.0034 mole) was added t o a s o lu tio n o f po tassium t-b u to x ld e
(1.25 g, 0.011 mole) in d r ie d hexamethylphosphoramide (30 ml) a t 0- 5° under
argon and th e so lu tio n was s t i r r e d fo r 4 min. M ethyl f lu o ro su lfo n a te (1 .2
ml, 1.85 g, 0.016 mole) vas added a l l a t once and s t i r r i n g o f th e m ixture
vas con tinued fo r 4 min. The re a c t io n m ixture was th e n quenched w ith
aqueous sodium b ica rb o n a te (150 ml) and th e aqueous la y e r vashed w ith e th e r
(4 x ). The combined e th e re a l la y e rs were vashed w ith aqueous sodium b ic a r -
b o rn te (2x ) , w ater (2x ) , s a tu ra te d b r in e ( lx ) , and f i l t e r e d th rough D r ie r i te .
C o n c en tra tio n under reduced p re s s u re y ie ld e d a crude yellow O il (0 ,5 4 g ,
99%) w hich co n ta in e d f i v e components hy g lc a n a ly s is (colum ns A and c).*
The m ajor p ro d u c t was 7 -m ethoxyb icyc lo [4 . 2 .23deca-2 ,4 ,7 ,9 - te t r a e n e ( l ^ ,
r e l a t i v e r e t e n t io n tim e = 1 . 0 ); o th e r p ro d u c ts v e re k e to n e 1 ( r e l a t i v e
r e t e n t io n tim e = l . l ) , 8 ,8 -d im e th y lb ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e
( 19; r e l a t i v e r e t e n t io n tim e «= 1 . 2 ) , 2 -m ethoxy-3 ,4 -d ihydronaph tha lene
( r e l a t i v e r e t e n t io n tim e = 1 .4 ) , and 2 - met h oxy naphtha l e ne ( r e l a t i v e r e te n
t i o n tim e b 1 .6 ) in th e p e rc e n t com position shown in T ab le V II. Analogous
r e s u l t s v e re o b ta in e d u s in g dim ethylform am ide a s so lv e n t ( se e T able l ) .
P u re m ethoxybetraene 17, v a s c o l le c te d by p re p a ra t iv e g lc j i r (n e a t) :
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 , -9 t -1 0 ) , 4 .5 0 (d d , IE, H a t C -8), 3 .4 0 ( s , 3H, m ethyl
C-H), and 3*20 (m, 2H, H a t C - l , - 6 ) . E xact m ass; c a lc d 160.0888; found
160.0886.A nal. Calcd f o r C11H12O: C, 8 2 .4 6 ; H, 7 .5 5 .
Pound: C, 82 .29 ; H, 7 .7 4 .
R e ac tio n s v e re ru n v a ry in g th e c o n ta c t tim e o f ke tone 1_ w ith po tassium
t-b u to x id e b e fo re quenching w ith m ethy l f lu o ro s u lfo n a te ; th e p ro d u c t d i s
t r i b u t i o n f o r b a se tim es o f 14 m in, 30 m in, 8 h r , and 2 4 .5 h r a re sum
m arized in T able, I .
*R eac tio n o f p -T e tra lo n e w ith P o tassium t-B u to x id e and D im ethyl S u lf a te i n
pim ethylform flm ide. p -T e tra lo n e (0 .5 8 g , 0 .004 mole) vas d is so lv e d in d ry
dim ethylform am ide (10 m l) and t r e a t e d w ith p o tassiu m t-b u to x id e (0 .3 5 6*
0 .005 m ole) d is s o lv e d in dim ethylform am ide (5 m l) f o r 15 min a t 0 ° .
D im ethyl s u l f a t e (O.5 8 g , 0 ,005 m ole) vas added and th e m ix tu re v as s t i r r e d
95
Table VH
Product D is tr ib u tio n from R eaction o f B icyclo[U . 2 .2]deca-2 , 4 ,9 - t r i e n-7-one
( l ) w ith Potassium t-B u to x id e and Methyl F lu o ro su lfo n a te in
Hexamethylphosphoramide
^ Product P ercen tage ■■■ ^
T ria l. i l i 12. 0 0 r’°°H3 C O ' 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
f o r 10 min. The m ixture vas poured in to aqueous sodium b ic a rb o n a te (125 ml)
and th e aqueous la y e r vas e x tra c te d v i th e th e r (3 x ). The combined e th e re a l
la y e r vas vashed v i th v a te r and s a tu ra te d b r in e , f i l t e r e d th rough B r ie r i te ,
and co n cen tra ted under reduced p re s s u re . D i s t i l l a t i o n o f th e re s id u e pro
duced a c le a r l iq u id (0.1*4 g ) , bp ll*4° (11 mm). Glc a n a ly s is (column A)
shoved th e p ro d u c t to be a m ixture c o n ta in in g 0- te t r a lo n e ( r e l a t iv e
r e te n t io n tim e « 1 . 0 , r e l a t i v e a re a $ » 5 . 0 ) , 2-methoxy-3 , l*-dihydronaph-
th a le n e (20, r e l a t i v e r e te n t io n tim e = 1 . 21, r e l a t i v e a re a ** o v e ra ll
y ie ld ■= 65#) and an u n id e n tif ie d component ( r e la t iv e r e te n t io n tim e = I . 65,
r e l a t i v e a re a % «= l ) o f mass m/e « 172 re p re se n tin g a d im e th y la tio n p ro
d u c t.
Pure 2-m ethoxy-3,U -dihydronaphthalene (20) vas c o lle c te d by p re p a ra tiv e
g lc ; i r (n e a t) : 1640 cm-1 (m); nmr: 6 6 .9 (m, 4h, a rom atic C-H), 5*5
( s , 1H, H a t C - l) , 3.6B (a , 3H, m ethyl C-H), 2 .9 (m, 2H, H a t C -4), and
2.1*0 (m, 2H, H a t C-3). Exact mass: ca lcd 160.0888; found 160.0890.
R eac tion o f B ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e ( l ) v i th Potassium t -
Butoxlde and Methyl F lu p ro su lfo n a te in Glyme. Ketone 1 (0 .10 g, O.OOO69
mole) vas d isso lv e d in d ry glyme (5 ml) and potassium t-b u to x id e (Table
V III) vas added a t 25°. A fte r s t i r r i n g th e s o lu tio n 4 min, m ethyl f lu o ro
su lfo n a te (T able VXIX) v as added a l l a t once and th e m ixture s t i r r e d an*
a d d it io n a l m inute. A f te r th e so lv e n t had been removed under reduced p re s
su re , th e re s id u e vas d is so lv e d in chloroform and analyzed by g lc (column
A).
The p roduct m ixture con ta ined 7 -met hoxyb icy c lo [U. 2 . 2^de ca-2> 1*, 7> 9 - te t r a
ene (IT , r e l a t i v e r e te n t io n tim e «= 1 .0 ) , ketone 1 ( r e l a t iv e r e te n t io n tim e «
Table VIII
Product D is tr ib u tio n from R eaction o f B ic y d o [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -T -o n e
( l ) v i t h Potassium t-B u to x id e and M ethyl F lu o ro su lfo n a te in Glyme
Experiment
Potassium t-B u to x id e Used
CH3OSQ2FUsed Yield® 3 1
■ P roduct P ercen tage - 1 18
-------s19
1 0 .10 g , 0.0009 n o le 0 .10 g , 0.0009 mole 0.110 g (100? )
P e r c e n t y ie ld c a lc u la te d on th e o r e t i c a l amount o f monomethylation.
98
1 .1 5 ) , 8 -m e th y lb ic y c lo [4 .2 .2 ]d e c a -2 ,b , 9 - tr ie n -T -o n e (18 , r e l a t i v e r e t e n t io n
tim e t= 1 .1 3 ) , and 8 ,8 -d im e th y lb ic y c lo [k .2 ,2 ]d e c a -2 ,k ,9 - tr ie n -7 -o n e ( 1%,
r e l a t i v e r e t e n t io n tim e = 1 .3 9 ) a s w e l l a s s e v e r a l u n id e n t i f ie d components
o f lo n g e r r e t e n t io n tim e s . P roduct a n a ly s is r e s u l t s a re shown in T ab le
V III .
P u re d im ethy lke tone 19 was o b ta in e d by p re p a ra t iv e g lc ; lj^ w as u n s ta b le
upon s ta n d in g and an a n a ly t i c a l sample could n o t be p re p a re d ; i r ( n e a t ) :
1700 ( s ) , 1380 (m ), 1370 (m ), and 1100 cm"1 (m ); nmr: 6 5 .9 (m, 6H, H a t
C-2, -3 , -U, - 5 , -9 , -1 0 ) , 3 .5 (m, 1H, H a t C -6 ), 2 .6 (m, 1H, H a t C - l ) ,
and 1 .2 (dy 6h , m ethy l C-H). Exact m ass: c a lc d rrJ+.lOlfk; found 17^.10^1 .
Mass s p e c t r a l a n a ly s is o f ke tone 1 as p r e p a ra t iv e ly c o l le c te d by g lc
from th e r e a c t io n m ix tu re in d ic a te d t h e p re se n c e o f m ethylketone 18 ̂ m/e =
160. The amount o f 18 p re s e n t was e s tim a te d by com parison o f p a re n t peaks
o f k e to n e 1 and 18 i n th e mass spectrum .
R e ac tio n o f 7-Metho3y b ic y c lo [ k ,2 .2 3 d eca -2 ,k , 7 , 9 - te t r a e n e ( 1 7 ) w ith Hydro
c h lo r ic A cid. M ethoxy te traene 17 (0 .0 7 g , 0 .000^3 mole) was d is so lv e d
in ch lo ro fo rm -d ( 0 .5 ml) c o n ta in in g 1% TMS and nap h th a len e ( ca 0 .1 1 g) aB
in t e r n a l s ta n d a rd s . I n i t i a l nmr a n a ly s i s showed an a ro m a tic :o le f in ic p ro to n
r a t i o o f 1 .0 :0 .8 2 . The s o lu t io n was t r e a t e d w ith h y d ro c h lo r ic a c id (3N,
0 .25 ml) and mixed c o n tin u o u s ly f o r 1 h r a t 2 5 ° . The aqueous la y e r was»
removed and th e o rg a n ic la y e r d r ie d o v e r anhydrous p o tass iu m carb o n a te .
The p ro d u c t m ix tu re was found t o be e x c lu s iv e ly naph tha lene and b i c y d o -
[ k .2 .2 ] d e c a - 2 ,k ,9 - t r ie n -7 - o n e ( l ) by nmr and g lc (column A) a n a ly s is ; nmr
a n a ly s is showed th e a ro m a tic :o le f in ic p ro to n r a t i o t o b e 1 . 0 : 0 . 83 , in d i
c a t in g e s s e n t i a l l y q u a n t i ta t iv e fo rm a tio n o f k e to n e 1.
99
R eaction o f B icyclo[U .2 .2 ]d e c a -2 ,h ,9 -tr ie n -T -o n e ( l ) v i th Potassium t -
Butoxlde and T r im e th y ls l ly l C hloride in Olyme. Ketone 1 (0 .292 g, 0.002
mole) vas d isso lv e d in d r ie d glyme (15 ml) and po tassium t-b u to x id e (0 .9 g,
0 .008 mole) vas added a l l a t once. A fte r s t i r r i n g th e so lu tio n f o r 3 min,
t r lm e th y ls i ly l c h lo rid e (1 .1 g, 0 .010 mole) vas added and th e m ix ture vas
s t i r r e d an a d d it io n a l 5 min. The so lv e n t v as removed under reduced p re s
su re and th e re s id u e d i s t i l l e d t o p rov ide a p a le yellow o i l , bp 65- 67°
(0 .05 mm), (0 .3 3 g, 7Qfi). 01c a n a ly s is (column A) shoved th e d i s t i l l a t e
t o be a m ix ture o f 7 - tr im e th y Is i lo x y b ic y c lo p . 2 .2 ]deca-2 , 1+, 7 ,9 ~ te trae n e
(21; r e l a t i v e r e te n t io n tim e = l A , r e l a t i v e a re a = 17, o v e ra l l y ie ld 72^)
and s ta r t in g .k e to n e 1_ ( r e l a t iv e r e te n t io n tim e = 1 ,0 , r e l a t iv e a re a = 1 .0 ) ,
P roduct 21 hydrolyzed on s tan d in g on ly a few hours in th e atm osphere. An
a n a ly t ic a l sample o f th e p roduct could no t be p rep ared ; i r (n e a t) : 1660
(m), 1200 ( s ) , 9^0 ( s ) , and 81*0 cm*1 ( b ) ; nmr: 6 5*9 ( m , 6H, H a t C-2,
-3 , A , -5 , -9 , -1 0 ), 1*.78 (dd, 1H, H a t C-8 ) , 3 .18 (m, 2H, H a t C - l , - 6 ) ,
and 0 .11 ( s , 9H, m ethyl C-H). Exact mass; ca lcd 218.1127; found 218.1123.
Thermal Rearrangement o f 7 -M e th o x y b icy d o [lf.2 .2 ]d eca -2 A ,7 ,9 - te t r a e n e (lj ).
Method.A. A s o lu t io n o f 7 -m ethoxyb lcyc loA «2 .2 Jdeca-2A ,7 ,9 - te tra e n e
(17; 0.25 g , 0 . 001U m ole) in d ry hexamethylphosphoramide (3 ml) v as heated
fo r 0 .5 h r a t 200°. A f te r coo ling t o 25°, th e m ixture vas poured in to
w ater (35 m l) c o n ta in in g aqueous sodium b ica rb o n a te (15 m l), and e x tra c te d
w ith e th e r (3 x ). The e th e r e a l e x tr a c ts were combined, vashed v i th aqueous
sodium b ica rb o n a te ( l x ) , w ater (2 x ), and s a tu ra te d b r in e ( i x ) . A f te r f i l t r a
t io n th rough D r ie r i te , th e s o lu tio n vas co n cen tra ted under reduced p re ssu re
t o give a m ix ture (0.2** g) by g lc a n a ly s is (column A) co n ta in in g th r e e
100
components corresponding in r e te n t io n tim e t o naphthalene ( r e la t iv e r e te n
t i o n tim e = 1 .0 , r e l a t i v e a re a « 1.7)# 7 -n e th o x y te traen e ( r e la t iv e
r e te n t io n tim e = 1.5# r e l a t i v e a re a = 7 .0 ) , and 2-m ethoxynaphthalene ( r e l a
t i v e r e te n t io n tim e » 2.5# r e l a t i v e a re a «= 1 .0 ) .
Method B. 7-Methoxyb icyclo [l* ,2 .2"]deca-2#4,7#9 - te tr a e n e (17, 0 .15 6#
0.0009 mole) vas p laced in a tu b e , evacuated t o a p re s su re o f 0.05 ®»# and
se a le d a t 25°. The compound vas th en heated t o 200° fo r 21 h r , th e tube
opened and th e p roduct m ix ture analyzed by g lc (column A) and p re p a ra tiv e
g lc fo llow ed by nmr and i r s p e c t r a l a n a ly s is . The m ixture co n s is ted
o f th r e e major and one minor p ro d u c ts : m ethanol ( r e l a t iv e r e te n t io n tim e **
0 .1 4 ) , naphthalene ( r e l a t iv e r e te n t io n tim e = 1 .0 , r e l a t i v e a re a = 5*75)#
7 -m ethoxytetraene ( r e l a t i v e r e te n t io n tim e = 1.5# r e l a t i v e a re a = 1 .0 ) ,
and 2-m ethoxynaphthalene ( r e l a t iv e r e te n t io n tim e ** 2.5# r e l a t iv e a re a =
2. 88).
P re p a ra tio n o f 2-Methoxyjtiapjitha.l^ene. 2-N aphthol (3 .4 g# 0.0237 mole) vas
d isso lv e d in hexamethylphosphoramlde (20 ml) and sodium hydride (1.05 g,
57? suspension , 0.025 mole) vaB added a t 25° a l l a t once. The m ixture vas
s t i r r e d f o r 0 .25 h r , m ethyl io d id e (1 .5 ? ®1# 0.025 mole) v as added a l l a t
once, and th e m ixture s t i r r e d f o r 5 niin. The r e a c t io n vas quenched v i th
v a te r (100 ml) and e x tra c te d v i th e th e r (3x ). The e th e r e x tr a c ts vere
vashed v i th aqueous sodium b ic a rb o n a te ( l x ) , v a te r ( l x ) , and b r in e ( lx ) and
f i l t e r e d through D rie r i t s . A f te r co n ce n tra tin g th e m ixture under reduced
p re s s u re th e re s id u e vas c l a r i f i e d v i th N o rite and r e c r y s ta l l i z e d from
e th a n o l t o y ie ld 2-m ethoxynaphthalene (3 .3 2 g , 89? ) , up 70 -71 .5° (rep o rted
mp 7 2 ° ) | i r (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,
m ethyl C-H).
B e ac tlo n o f B ic y c lo [4 .2 .2 ]d e c a -2 ,U ,9 - tr ie n -7 -o n e ( l ) w ith Lead T e tr a a c e ta te .1—i_j-i_r_n-rLn_nji_n_fuijijLinirifirM^if¥~i- ~ ~ — —■— w~ 1 —~—g-n—1 riri ru~. r~> n n n r r n_ri_rr~ — j~u~ _il_i ji_n_r_n..r_r_n_n-fi_r̂ ^-M~rf*̂~f
Ketone 1 (0 .5 0 g , 0 .0031+ m ole) and le a d t e t r a a c e t a t e (1 .5 g , 0 .003h mole)
v e re re f lu x e d in a c e t i c a c id (20 m l) f o r 5 h r . The m ix tu re was poured in to
v a te r (150 m l), e x tr a c te d v i t h e th e r (3x ) and m ethylene c h lo r id e ( lx ) and
th e combined o rg an ic e x t r a c t s v e re vashed v i t h v a te r (2 x ) , aqueous sodium
b ic a rb o n a te (2 x ) , and b r in e ( l x ) . A f te r rem oval o f th e so lv e n t under r e
duced p re s s u re and s to ra g e a t -2 0 ° , th e crude p ro d u c t c r y s t a l l i z e d (0 .7 0 g,
100$); g lc a n a ly s is (colum n A) shoved th e m a te r ia l t o b e 99? p u re . D i s t iH a
t i o n o f th e crude p ro d u c t a ffo rd e d a n t i -8 -a c e to x y b ic y c lo f^ . 2 .2 Jd e c a -2 ,k ,9 -
t r ie n -7 -o n e ( 26 )* p a le y e llo w c r y s t a l s , b p ,9^ -96° (0.01; mm), mp 81-82°;
i r (KBr p e l l e t ) ; 17^0 ( s ) and 1220 cm-1 ( s ) ; nmr: 6 5*9 (w, 6h, H a t C-2,
-3 , - 1*, -5# -9 , -10)* 5 .35 (o . 3H, H a t C -8), 3 .6 (m, 2H, H a t C - l , - 6 ) ,
and 2 .0 ( s , 3H, m ethyl C-H). Exact maos: c a lc d 201|.0786 ; found 20U.O783 .
A nal. C alcd f o r C12H12O3 : C, 7 0 .6 0 ; H, 3*38*
Found: C, 7 0 .7 1 j H, 5*67*
A cid -C ata lyzed R eac tio n o f a n t i - 8-A cetoxyblcycloCU .2 .2 ld e c a -2 . U.9 - t r i e n - 7 -
one ( 26 ) v i th M ethanol. A cetoxyketone 26 (0 .2 0 g, 0 ,0001 mole) in m ethanol
(10 ml) c o n ta in in g 25 g ra in s o f £ - to lu e n e s u lfo n lc ac id vas re f lu x e d 7 h r .
A f te r th e so lv e n t had been removed under reduced p re s s u re , th e re s id u e v as
d is so lv e d in m ethylene c h lo r id e and vashed v i t h aqueous sodium b ic a rb o n a te .
The s o lv e n t vas removed under reduced p re s s u re a f t e r f i l t r a t i o n th ro u g h
102
D r ie r i te t o y ie ld a yellow o i l (0 .18 g, 100$) which was a 93 :7 m ixture o f
isom ers (column A ). Pure syn-8-methoxybic y c lo l4 .2 .2~)deca-2.4 .Q - tr le n - 7 -o n e
(28) was ob ta ined by p re p a ra tiv e g lc ; i r (n ea t) 1720 cm"1* nmr: 6 5 .8 (m,
6h, H a t C-2, -3 , -4 , -5 , -9 , -1 0 ), 4 .05 (dd, 1H, H a t C -8), 3 .7 (m, 2H,
H a t C -l, - 6 ) , and 3*35 ( s , 3H, methoxy C-H). Exact mass: c a lc d 176.0837*
found 176.0835.
Anal. Calcd fo r C u £ i2 0 a : C, 74 .98 ; H, 6 .86 ,
Pound: C, 75.15* H, 6 . 89 .
R eaction o f syn-8-Methoxyb ic y c lo l .2 .2 1 d e c a - 2 .4 .9 - tr ie n -7 -o n e ( 28) w ithSB
2 ,4 -D in ltropheny lhyd razine . Methoxyketone 28 (0 .10 g, O.OOO57 mole) was
t r e a te d w ith excess 2 ,4 -d in itro p h en y lh y d ra z in e re a g e n t. The crude yellow
p roduct (0 .20 g, 100$) was r e c r y s ta l l i z e d from 1 ;1 e th y l a c e ta te /e th a n o l
t o produce pure syn-8 -m ethoxyb icyclo [4 .2 .21deca-2 ,4 t 9 - tr ie n -7 -o n e 2 ,4 -
d in itropheny lhydrazone , mp 225-226.5°, mass spectrum m/e *= 356 .
A nal. Calcd fo r Ci7H i6H40s : C, 57.30; H, 4 .53 ; N, 15-72.
Found: C, 57.35; H, 4.51* N, 15 .90 .
Attempted A cid-C atalyzed H ydro lysis o f an ti-8 -A c e to x y b ic y c lo [4 .2 .2]deca-
2 ,4 ,9 - tr ie n -7 -o n e (26) in Dlmethylformamide-W ater. Acetoxyketone 26 (0 .2 g,
0 ,001 mole) in w ater (5 m l) - dimethylformamide (5 ml) c o n ta in in g £ - to lu e n e -
su lfo n ic a c id (0 .0 1 g) was warmed t o 110° f o r 8 h r . The m ix tu re was poured
in to w ater (50 m l), e x tra c te d w ith e th e r (3x) and th e combined e th e r la y e r
was washed w ith w ater (3 x ), aqueous sodium b ica rb o n a te and s a tu ra te d b r in e .
F i l t r a t i o n th rough D rier i t e and co n ce n tra tio n under reduced p re s su re
a ffo rd ed a ye llow o i l (O.1 6 g) which was alm ost e x c lu s iv e ly s t a r t i n g ketone
103
26 (85^) by g lc and nmr a n a ly s is . The minor p roducts (3 peaks by g lc )
showed arom atic p ro to n nmr resonance .
R eac tion o f B lcyclo tU .g .23^gca-2yUf 9-trlen~ T -one ( l ) w ith I soanyl N i t r i t e37
and Potassium t-B u to x id e . Ketone 1 (1 .0 2 g, 0.007 mole) in t -b u ta n o l (10
ml) was added t o potassium t-b u to x id e (7 .5 g> 0 .0 7 mole) in t -b u ta n o l (65
ml) and th e s o lu t io n was s t i r r e d f o r O.75 h r under argon. Isoam yl n i t r i t e
(3*0 Hi) was added and s t i r r i n g was continued f o r 1 h r ; iBoanyl n i t r i t e
(2 .5 ml) was a g a in added and th e m ix ture was s t i r r e d f o r 0 .5 h r . The re a c
t i o n m ixture was poured in to e th e r - ic e v a te r and th e aqueous la y e r vas
e x tra c te d w ith e th e r (2x). The aqueous la y e r v as a c id if ie d v i th a c e t ic a c id
and r e - e x t r a c te d w ith e th e r (3 x ) . The l a t t e r e th e r e a l la y e rs were vashed
w ith aqueous sodium b ica rb o n a te ( 2x ) , b r in e ( l x ) , f i l t e r e d th rough D r ie r i te ,
concen tra ted tinder reduced p re s s u re , and f i n a l ly d ried i n vacuo overn igh t
t o y ie ld th e crude product (O.75 g, 6396) . S o lu tio n in methylene c h lo r id e ,
c l a r i f i c a t i o n w ith N o rite , and r e c r y s t a l l i z a t i o n from 1 :2 m ethylene c h lo r id e -
cyclohexane produced pure b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 ,8 -d io n e mono-
oxime (22 ), a yellow powder, mp 178-178.5°; i r (KBr): 3300 ( s ) , 1710 ( s ) ,
and 1690 cm"1 ( s ) ; nmr: 6 5 .9 (m, 6h, H a t C-2, - 3 , -4 , -5 , -9 , -1 0 ), 4 .3
(dd , 1H, H a t C-6 ) , and 3 .7 (m, H a t C - l) . Exact mass; c a lcd 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.
R eaction o f B ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 ~ tr ie n -7 ,8 -d lo n e Monooxime (33) v i th o-
diam ine ( 0 .3 1 g , 0.0029 mole) v e re re f lu x e d in e th a n o l (10 ml) - a c e tic
104
ac id (10 ml) f o r 1 h r . Qfce re a c tio n m ixture vas cooled and poured in to
v a te r ; th e p roduct vas f i l t e r e d and a i r d ried (0 .30 g, 46%). R e c ry s ta l l i
z a tio n from m ethanol produced th e pure quinoxaline d e r iv a tiv e o f b ic y c lo -
[4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 ,8 -d io n e (£4)> 194.5-195°J i r (KBr p e l l e t ) :
1500 (m), 950 ( s ) , 760 ( s ) , and 730 cm"1 ( s ) ; nmr: ' fi 7 .85 (AaB2 , 4H,
arom atic C-H), 6 .1 (m, 6H, H a t C-2, -3 , -4 , -5 , -9 , -1 0 ) , and 4 .35 (m, 2H,
H a t C -l, - 6 ). Exact m aB s: ca lcd 232.1000; found 232.1004.
A nal. Calcd fo r CieHi2N2 : C, 82.73* H, 5.21; N, 12.06.
Found: C, 82.48; H, 5.19* N, 12.10.
R eaction of B ic y c lo [4 .2 .2 ]d e o a -2 ,4 ,9 - tr ie n -7 -o n e ( l ) v i t h Sodium Methoxide
and M ethyl Form ate. Ketone 1 (0 .8 8 g , 0.006 mole) vas added to a suspension
of f r e s h ly p repared sodium methoxide ( 1.30 g , 0.024 mole) in d ry e th e r
(100 m l). A fte r a d d itio n o f m ethyl form ate (1 .4 3 g, 0.024 m ole), th e re a c t io n
m ixture vas s t i r r e d fo r 22 h r . Cold h y d ro ch lo ric ac id (3N, 30 ml) vas
added and th e m ixture e x tra c te d v i th e th e r (2 x ). The combined e th e re a l
vashes v e re e x tra c te d v i th v a te r ( 3x ) , s a tu ra te d b r in e ( lx ) , and f i l t e r e d
through D r ie r i te . C oncentration o f th e so lu tio n y ie ld ed a brovn o i l (l.OO
g> 95%) vh ich com pletely s o l id i f i e d from pentane to a ta n so lid . A n a ly ti
c a l ly pure 8 -fo rn y lb ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e ( 38) vas prepared
by e lu t io n through a s i l i c a g e l column (25% e th e r /75% cyclohexane so lv e n t)
and subsequent c r y s ta l l i z a t io n from pentane a t -78°, mp 58-57°; i r (KBr
p e l l e t ) : 1660 ( b ) , 1580 ( a ) , and 1120 cm-1 (m); nmr: 6 8 .1 ( a , 1H, a ld e -
hydic C-H), 5-9 (m> 7H, H a t C-2, -3 , -4 , -5 , - 8 , -9 , -1 0 ) , and 3 -5 (m, 2H,
H a t C - l , - 6 ) . Exact mass: ca lcd 174.0681; found 174.0683;
Anal. Calcd fo r CnHio02 : C, 74.84; H, 5*79.
Found:. C, 75*55; H, 5*75*
R e ac tio n o f 8 -F o rm y lb icy c lo fli.2 .2 3 d eca -2 * U * 9 -trien -7 -o n e (38) v i t h
105
H ydrazine. Formy3ketone 38 (O.52 g , 0 .003 mole) was d is so lv e d in
e th a n o l ( l m l). Anhydrous h y d raz in e (0 .13 g , 0.00U m ole) in e th a n o l (3 ml)
vas added ( p r e c ip i t a t i o n occu rred im m ediately) and th e s t i r r e d m ix tu re was
re f lu x e d 18 h r . The d a rk s o lu t io n was cooled* poured in to v a te r (50 ml)*
and e x tra c te d v i t h e th e r ( 5>0 • The combined o rg an ic la y e r was vashed w ith
s a tu r a te d t r i n e , f i l t e r e d th rough D r ie r i te * and c o n ce n tra te d . The d a rk o i l
( 0 .3 2 g) was e lu te d th ro u g h a s i l i c a g e l column ( e th y l a c e ta te s o lv e n t) t o
y ie ld a d i f f i c u l t l y c r y s t a l l l z a h l e o i l (O.UU g* 86$ ). A n a ly t ic a l ly pure
3 * 4 -d ia z a tr ic y c lo [5 » ^ * 2 .0 a ,6 ]trideca-2 ,5*8*10*12-penfcaene (39) was p rep a red
t y two r e c r y s t a l l i z a t i o n s from henzene/cyclohexane* mp 106-107°; i r (KBr):
3250 cm"1 ( s ) ; nmr:- 8 9*25 (h r s , 1H* N-H, s h i f t i s c o n c e n tra tio n depen
d e n t, d isa p p e a rs upon a d d it io n o f Da 0 ) , 7 .1 5 (b , 1H, H a t C -5), 5 .9 (m, 6h*
H a t C-8* -9* -10* - H , -12* -1 3 ) , and k.O (m, 2H* H a t C -l, - 7 ) . Exact
mass: c a lcd 1 7 0 .0 8 ^ ; found 170.081*7.
A nal. C alcd f o r CxiHioNa : C* 77 .62 ; H, 5 .92.
Found; C, 77*35* H, 6 .O9 ,
R e ac tio n o f 8 -F o rm y lb icy c lo [ k . 2 . 2 ]d e c a -2 ,4 , 9 - t r ie n -7 -o n e (58 ) w ith T osy l
A zlde and T rie th y la m in e . F o rny lke tone ( l .O g, 0 .0575 mole) was d is so lv e d
in m ethylene c h lo r id e (30 ml) and tr ie th y la m in e (1 .2 2 g* 0 .12 m ole) and to s y l
a z id e ( l . l g* 0 .0575 m ole) v e re added a t 2 5 ° . The m ix tu re was s t i r r e d f o r
4 h r . P o tassium hydrox ide (5 g) in w ater (60 ml) was added and th e m ix ture
vas s t i r r e d an a d d i t io n a l 15 min. A fte r s e p a ra t io n o f th e la y e r s and subse
quent e x t r a c t io n o f th e aqueous l a y e r w ith m ethylene c h lo r id e (2 x ) , th e
combined o rg an ic phases v e re vashed w ith v a t e r (2x) and d r ie d o v e r anhydrous
106
p o tassiu m c a rb o n a te . C o n cen tra tio n y ie ld e d a dark brown o i l (0 .9 2 g) which
c o n ta in e d th e p ro d u c t and t o s y l a z ld e a s in d ic a te d by m icro t i c a n a ly s is
on s i l i c a g e l 0 w ith 1 :1 e th e r-h ex a n e s o lv e n t. S e p a ra tio n on a s i l i c a g e l
column ( 1:3 e th e r-c y c lo h e x a n e ) y ie ld e d 7 -d ia z o b ic y c lo [ 4 .2 .2 ]d e c a -2 ,4 ,9 -
t r i e n -8- one ( 37 ) a s a b r ig h t ye llow l iq u id w hich c r y s t a l l i z e d a t - 20° and
rem ained s o l id upon rowarmlng (0 .5 2 g , 55^)* mass spectrum (P-N2 ) m/e = 144;
i r (n e a t) : 21J0 ( s ) , I 65O ( s ) , 1350 ( s ) , and 1220 cm -i ( s ); nmr: 6 5-9
(m, 6H, H a t C-2, -3 , -4 , -5 , -9 , - 1 0 ) , and 3*65 (m, 2H, H a t C - l , - 6 ) .
P h o to ly s is o f 7 -D la z o b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -8 -o n e (37) i n W ater-
D loxane. D iazoketone £7, (°*75 S» 0 .0044 m ole) was d is so lv e d in £>-dloxane
(50 m l) and w a te r (25 ml) and th e s o lu t io n was degassed w ith a stream o f
argon f o r 0 .5 h r . The s o lu t io n was th e n i r r a d ia te d w ith a 450 w a tt medium
p re s su re Hanovia lamp in a l l q u a rtz equipm ent fo r 6 h r . Upon com pletion
o f th e experim en t, ^7 was a b se n t a s ev idenced by th e la c k o f e v o lu tio n o f
n itro g e n upon a d d it io n o f a drop of c o n c e n tra te d h y d ro c h lo r ic a c id t o an
a l iq u o t o f th e r e a c t io n m ix tu re . The s o lu t io n was c o n c e n tra te d (20 ml)
under reduced p re s s u re , and th e n th e r e s id u e was t r i t u r a t e d w ith aqueous
po tassium ca rb o n a te and e x tr a c te d w ith e th e r . The aqueous la y e r was a c id i
f i e d w ith h y d ro c h lo r ic a c id (3N) and e x t r a c te d v i th e th e r (5 x ) . The com
b in ed e th e r e a l la y e r v as washed w ith v a te r and s a tu ra te d b r in e and th e n
f i l t e r e d th ro u g h D r i e r i t e . C o n c e n tra tio n o f th e o rg an ic phase y ie ld e d a
s in g le p ro d u c t (0 .4 3 Bt 6 l %) a8 ev idenced by m icro t i c a n a ly s is (1 :1 e th e r -
p e tro leum e th e r s o lv e n t) .
The p ro d u c t vas f i l t e r e d th ro u g h a s h o r t column o f s i l i c a g e l and r e
c r y s t a l l i z e d from e th e r-p e tro le u m e th e r a t - 78° t o p ro v id e p u re b ic y c lo -
107<43
[4 .2 .11nona-2> 4 ,7 -trlen -ja jm -9 -carboxy llc a c id (4 0 ), mp 173-174.5° ( l i t
mp 173-174°), a s v h i te c ry s ta l s ; i r (KBr); 3150 (b r , s ) , 1730 (a ) , and
1680 cm"1 ( s ) ; nmr; 6 11 .2 ( s , 2H, -C00H, s h i f t i s c o n ce n tra tio n depen
d e n t) , 6 .1 (m, 4H, H a t C-2, -3 , -4 , - 5 ) , 5.25 (d , 2H, H a t C-7, - 8 ) , and
3 .3 («, 3H, H a t C - l, - 6 , - 9 ) . Exact mass; ca lcd 162.0681; found 162. 0683,43
The m a te r ia l vas id e n t ic a l in a l l re s p e c ts t o t h a t rep o rte d by Sanders.
R eaction of B lc y c lo [4 .2 ,l]n o n a -2 ,4 ,7 - tr le n -s y n -9 -c a rb o x y llc Acid (40)
v i th Diazomethane. Crude a c id 1*0 (O.35 g , 0.0022 mole) vas d isso lv e d in
e th e r (50 ml) and t r e a te d v i th dlazomethane (0 .3 M; 30 ml, excess) a t 25°
and s t i r r e d fo r 0 .5 h r . Formic a c id vas added t o d e s tro y excess d iazo -
methane. The e th e r la y e r vas e x tra c te d v i th aqueous sodium b ic a rb o n a te ,
s a tu ra te d b r in e , and f i l t e r e d through D r ie r i t e . C oncen tra tion under r e
duced p re ssu re y ie ld e d a yellow o i l ( 0 .4 l g) which vas ca 99# pure by g lc
a n a ly s is (column A). D i s t i l l a t i o n a ffo rd ed pure m ethyl b icy c lo [4 .2 .1 ]n o n a -
2 , 4 , 7- t r len -syn- 9 -ca rb o x y la te (4 l ) as a v h i te s o l id , bp 66 . 5° (0 .05 ®®)*
mp 27-29°i (0 .37 St 93#); i r (n e a t) : 1720 ( s ) , 1220 ( s ) , and 1205 cn r1 ( s ) ;
nmr; 6 5 .9 (m, 4h, H a t C-2, -3 , -4 , - 5 ) , 5-15 (d , 2H, H a t C-7, - 8 ) , 3 .5
( s , m ethyl C-H) superimposed on 3 .3 (n , H a t C -l, - 6 , -9 , t o t a l 6h ) .
Exact mass: ca lcd 176.0837; found 176.0840.
Anal. Calcd fo r CuRi^Os; C, 74.98j H, 6 . 86 .
Found; C, 75 .19; H, 6 .9 0 .
R eaction of 7 -D ia z o b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -8 -o n e (%[) v i th A cetic
Acid. D iazoketone £7, (0 .8 8 g, 0.0051 mole) vas d isso lv ed in a c e t ic a c id
(12 ml) and s t i r r e d a t 25° fo r 4 h r . The r e a c t io n f la s k v as f i t t e d v i th a
108V igreux column ana d i s t i l l i n g head and th e r e a c t io n m ix tu re vas d i s t i l l e d
(25° p o t te m p e ra tu re , 6 mm) t o remove ex cess a c e t i c a c id . The column was
removed and th e r e s id u e v as d i s t i l l e d t o produce p u re exo-2 -a c e to x y b lc y c lo -
[5 .2 .1 Jd e c a -3 » 5 > 8 -tr ie n -1 0 -o n e (44) a s a c le a r l iq u id (0 .8 7 g , 84?6),
102- 103° ( 0 .1 mm); i r ( n e a t) ; 1760 ( s ) , 1740 ( s ) , 1370 (m), and 1230 cm"1
( s ) ; nmr: 5 5 .9 (m, 6h , H a t C-3, -4 , -5 , -6 , -8 , - 9 ) , 5 .00 ( t , 1H, H a t
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,
m ethyl C-H); uv: 200, 225, and 285 nm (e = 6080, 4000, and 600).
E xact mass; c a lcd 204.0786; found 204.0788.
A nal. Calcd f o r C12H12O3 : C, 7 0 .6 0 ; H, 5*88.
Found: C, 7 0 .8 0 ; H, 5 . 83 .
A ttenrpts t o p u r i f y 44 ̂by p re p a ra t iv e g lc (column A, in j «= 250, column
= 225) produced e n d o -6 - (c is -2 , -a c e to x y v in y l)-c is - 'b ic y c lo C 3 .3 . 0 ] o c ta - 3 ,7 -
d ien -2 -o n e (57) a s th e m ajor p ro d u c t (93^) a s a p a le yellow s o l id , mp 69-
71°- Rearrangem ent o f 4-5 v as tem p era tu re dependen t; o n ly 70J6 o f th e r e
a rran g ed p ro d u c t was form ed a t 150° ( i n je c t o r = 200°) w h ile 85^ co n v ersio n
was observed a t 180° ( i n je c t o r ■ 23 0 °); i r (KBr): 1760 ( s ) , 1695 ( a ) ,
1220 ( s ) , and 1040 cm"1 ( s ) ; nmr: 6 7 .5 (dd , 1H, H a t C -4 ), 7 .1 4 (dd , 1H,
H a t C - 2 ') , 6 .0 8 (dd , 1H, H a t C -3 ), 5 .80 (m, 1H, H a t C-7 o r - 8 ) , 5 .50
(m, 3H, H a t C-7 o r - 8 ) , 4 .6 9 (dd, 1H, H a t C - l ) , 4 .14 (b r t , 1H, H a t 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 ^ 6 r 208 nm (e mnv. = 3 1 ,5 0 0 ). E xact mass: c a lc d 204,0786; found
204.0788.
A nal. Calcd f o r C12H12O3 : C, 7 0 .6 0 ; H, 5*88.
Found: C, 7 0 .6 8 ; H, 5 .9 0 .
109
H ydro lysis o f endo- 6- ( c i s - 2 ♦ -a c e to x rv ln y l) - c i s -b lcycloT 3 .3 .0 1 o c ta -3 .7 -
d ien-2-one ( ^J_)« Acetoxyketone %J_ (5 3 ,1 mg, 0,00026 mole) was dissolved,
in chloroform -d (0 ,5 ml) and t r e a te d w ith w ater (3 d rops) co n ta in in g
t r i f lu o r o a c e t i c anhydride ( l drop) f o r 6 days w ith continuous sw irlin g )
th e r e a c t io n was m onitored by nmr. The aqueous la y e r vas removed) th e o r
ganic la y e r was d r ie d over anhydrous po tassium carbonate and co n cen tra ted
- under reduced p re s su re t o produce a c le a r o i l (39.0 mg) which con ta ined
two m ajor components by g lc a n a ly s is (column A), The p roduct endo-6- ( l * -
o x o e th y l)- c l s -b lc y c lo r3 .3 .0 1 o c ta -3 ,7 -d len -2 -o n e (60 , r e l a t i v e r e te n t io n
tim e = 1 . 0 , r e l a t i v e a re a $ = 60, o v e ra l l y ie ld = 75$ ) and s t a r t i n g m a te r ia l
( r e l a t iv e r e te n t io n tim e «= 1 . 7 , r e l a t i v e a re a $ = 15) were c o lle c te d by
p re p a ra tiv e g lc ,
Ketoaldehyde 60 was p u r i f ie d w ith la rg e I o b s in m a te r ia l t o y ie ld
8 mg o f pure compoundj i r (n e a t) : 1715 ( s ) and 1700 cm- 1 ( s ) ; nmr: 6
9 .8 0 ( s , 1H, H a t C -2), 7 .32 (dd, 1H, H a t C-4), 6 .02 (dd, IE, H a t C -3),
5 .6 (m, 2H, H a t C-7, - 8 ), 3 .65 and 3 .45 (two m, 3H, H a t C -l, - 5, - 6 ) ,
and 2 .6 (b r d , 2H, H a t C-2’ ) . Exact mass: calcd 162.0681) found
162.0683.
C a ta ly tic Hydrogenation of exo-2-A cetoxybicyclo[5*2.1 ]deca-3 , 5, 8- t r i e n -
10-one (44 ). Acetoxyketone 44 ( l .0 6 g, O.OO52 mole) was d isso lv e d in
a b so lu te e th an o l (100 m l), 10?> pallad ium on carbon (0 .1 g) was added and
th e m ixture was p laced in a P a r r ap p ara tu s (P - 50 lb ) f o r 6 h r . The re a c
t i o n m ixture was f i l t e r e d th rough C e li te t o remove th e c a ta ly s t and th e■
so lv e n t removed under reduced p re s su re . The re s id u e was tak en up in e th e r ,
vashed w ith s a tu ra te d b r in e , f i l t e r e d th rough D r ie r i te and co n cen tra ted
110
under reduced p re s su re to y ie ld a c le a r o i l (1 .07 g ) . The m a te r ia l vas
e lu te d through a s i l i c a g e l column, f i r s t v i th e ther/cyclohexane ( l : 3 ) t o
remove in p u r i t i e s and th e n w ith e th e r t o y ie ld a c le a r o i l (0 ,80 g, 73%)
which c r y s ta l l i z e d on s tan d in g .
A n a ly tic a lly pu re exo-2-acetoxyb icyclo f5 .2 .11decan-10-one ( 50) vas
c o lle c te d by p re p a ra tiv e g lc (column A) as a v h i te s o l id , mp i r
(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 l ip h a t ic C-H). E xact mass:
c a lcd 210. 1256| found 210 . 1260 .
Anal. Calcd f o r CipHiqO^: C, 68 .55; H, 8 . 63#
Found: C, 68 .28; H, 8 .5 7 .
R eac tion of exo-2 -A ce to x y b lcy c lo [5 .2 .l]decan-10-one ( 50 ) v i th Sodium Hydroxide
in M ethanol-W ater. Acetoxyketone 50 (0 .70 g, O.OO53 mole) was d isso lv ed
in h o t m ethanol (10 ml) and sodium hydroxide ( l p e l l e t , ca O.OOh mole)
d isso lv e d in v a te r ( l ml) v as added. The re a c t io n vas s t i r r e d a t 25° fo r
1 day. The m ix ture vas poured in to v a te r (50 ml) and th e aqueous la y e r
e x tra c te d w ith e th e r (3 x ). The combined e th e r e x tra c t vas washed w ith
s a tu ra te d b r in e , f i l t e r e d th rough D r ie r i te , and concen tra ted under reduced
p re s su re to y ie ld an o i l (0 .5 2 g) which vas g re a te r th an 99% pure by g lc
a n a ly s is (column A). The m a te r ia l vas e lu te d th rough a s i l i c a g e l column
(g ra d ie n t e lu t io n : 20% ether-cyc lohexane , 50% ether-cyc lohexane , e th e r)ot o produce a c le a r o i l which vas r e c r y s ta l l i z e d from pentane a t -78 t o
p rov ide exo-2-hydroxybicyclo[5 .2 .1 ]decan -10-one ( 51) , a pure v h i te c r y s ta l
l in e p ro d u ct, rap 47-^8 .5° (0 .2 7 g, 50%); i r (KBr): 3U5O (s ) and 173° cm"x
( s ) . Exact mass: c a lcd 168.1150; found 168.1153*
I l l
O xidation o f exo-2-H ydroxybicyclor5 .2 . l*)de can-10-one (51) w ith Chromic
A cid. Hydroxyketone j j l (0 .20 g, 0.0012 mole) v as d isso lv ed in acetone
(10 m l). Chromium t r io x id e d isso lv ed in 25$ s u l f u r ic a c id (2 .6 M, 1 ml,
0.0026 mole) was added d ropv ise and th e m ixture was s t i r r e d ra p id ly fo r
0 .5 h r . Methanol (0 .1 5 ml) vas added t o quench excess o x id an t, and th e
m ixture was d i lu te d w ith 2 volumes of w ater and e x tra c te d w ith e th e r (tac).
The aqueous la y e r was a c id i f ie d and e x tra c te d w ith e th e r ; th e aqueous
la y e r was th e n made a lk a lin e and re -e x tra c te d w ith e th e r . The combined
e th e re a l e x tr a c t was washed w ith v a te r , aqueous sodium b ica rb o n a te , and
s a tu ra te d b r in e . F i l t r a t i o n th rough D r ie r i te and co n cen tra tio n under r e
duced p re s su re p rov ided a yellow l iq u id (0 .2 1 g , 100$) which con ta ined one
component based on g lc a n a ly s is (column A). The m a te r ia l was p u r i f ie d by
p re p a ra tiv e g lc to y ie ld pure b ic y c lo [5 .2 . l]d ecan -2 ,1 0 -d io n e ( 52) a s a
c le a r l iq u id ; i r (n e a t) ; 173° ( s ) a^d 1700 cm"1 ( s ) . Exact mass; ca lcd
166. 099^; found l 66 . 0996> The p roduct was d is s im ila r in a l l re sp e c ts to
b ic y c lo [4 .3 . l]d ecan -7 ,1 0 -d io n e (5?) p repared from 1-m orpholinocycloheptene44
and ac ro y l c h lo rid e as p rev io u s ly d escrib ed .
Anal. Calcd f o r CioHrtQg: C, 72 .26 ; H, 8.1*9.
Found; C, 72.13; H, 8 . 53.
R eaction o f 7 -Diazob icyclo [U . 2 .2 ]d eca-2 , U, 9 - t r ie n -8 - one (37 ) w ith Hydrogen
C h lo ride . D iasoketone (0 .69 g» 0.00U mole) was d isso lv ed in dry e th e r
(10 ml) and hydrogen c h lo rid e was bubbled th rough th e s o lu t io n fo r 15 min.
The so lu tio n vas allow ed to s ta n d an a d d it io n a l 13 min; th e r e a c t io n mix
tu r e vas th e n d i lu te d w ith e th e r (1*0 ml) and e x tra c te d w ith v a te r (2x ),
aqueous sodium b ica rb o n a te ( lx ) , and s a tu ra te d b r in e . The organ ic la y e r was
112
f i l t e r e d th rough D r ie r i te and co n cen tra ted under reduced p re s su re t o y ie ld
exo-2 -c h lo ro b lq y c lo r5 .2 . H d e c a -3 . 5 .8- t r l e n - 10-one ( 54) as a ye llow l iq u id«
(0.68 g , 94$) • The compound was extrem ely la b ile # a l l a ttem p ts t o p u r ify
th e m a te r ia l v e re unsuccessful# i r (n e a t) : 1740 cm*1 (s)# nmr: 6 5*9 (n»
7H, H a t C-2, -3 , -If, -5 , - 6 , - 8 , -9 ) and 3 .2 (m, 2H, H a t C -l, - ? ) . Exact
mass: ca lcd 180.0342# found I 8O.O3H .
A ttem pts t o d i s t i l l o r p re p a ra tiv e ly g lc ch loroketone le d t o quan
t i t a t i v e rearrangem ent t o e n d o -6 -(2 '-£ is -c h lo ro v in y l) -c iB -b lc y c lo [3 .3 -0 ]“
o c ta -3 , 7 -d ie n -2 -one (g8 ) a s a yellow liq u id # i r (n e a t) : 1700 cm*1 (s)# nmr:
6 7 .5 (dd, 1H, H a t C -4), 5 .9 (m, 5H, H a t C-3, -7 , - 8 , - 1 ' , - 2 ' ) , 2 .75
(m, 2H, H a t-C -5 , - 6 ) , and 2 .5 (m, 1H, H a t 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 .
C a ta ly t ic Hydrogenation o f exo -2 -C h lo rob icyc lo [5 .2 . l ] d e c a - 3 ,5 ,8 -tr le n -1 0 -o n e
(54). Crude ch loroketone ^4_ (0 .48 g , 0.0027 mole) was d isso lv ed in ab so lu te
e th an o l c o n ta in in g 10$ pa llad ium on carbon (0 .06 g) and th e m ixture was
p laced in a P a r r appara tu s (hydrogen p re ssu re = 50 lb ) fo r 6 h r . The reac
t io n m ix tu re was f i l t e r e d th rough C e li te and th e re s id u e was vashed v i th
e th e r (2 x ) . The f i l t r a t e was co n cen tra ted under reduced p re s su re . The#
re s id u e v as taken up in e th e r and vashed v i t h s a tu ra te d b r in e , f i l t e r e d
through D r ie r i t e and co n cen tra ted again t o y ie ld a yellow o i l (0 .4 0 g ) .
Micro t i c a n a ly s is ( l : 9 e th y l a c e ta te ;p e tro le u m e th e r ) o f th e o i l shoved
two components, v a lu e s .o f ,0 .8 and 0 . 5 .
The crude p ro d u c t was e lu te d th ro u g h a s i l i c a g e l column (5$ e th y l*■
a c e ta te -p e tro le u m e th e r s o lv e n t) ; th e f i r s t m a te r ia l o f f th e column weighed
0 .2 8 g and was found t o h e a m ix tu re o f a s a tu r a te d and u n sa tu ra te d ke tone
by g lc (column A ), i r , and maBS s p e c t r a l measurement (m /e = 150, 152) .
The m ix tu re o f k e to n e s was d is so lv e d in a b so lu te e th a n o l (35 ml) con
t a in in g 10$ p a lla d iu m on carbon (0 .0 5 g) and rehyd rogenated in an atm os
p h e r ic p re s s u re h y d ro g en a to r. Hydrogen u p tak e ceased a f t e r 2 h r and th e
p ro d u c t m ix tu re worked up a s b e fo re t o y i e ld an o i l ( 0 .2 5 g, 6l $ ) which
was g r e a te r th a n 98$ p u re b y g lc a n a ly s i s . P u re b ic y c lo [5 .2 .l ]d e c a n - lO -
one (££) was c o l le c te d by p r e p a ra t iv e g lc and p o sse sse d s p e c t r a l p r o p e r t ie s4 3
i d e n t i c a l t o th o se re p o r te d f o r th e p re v io u s ly r e p o r te d compound, mass4 3
spectrum m/e = 152; i r ( n e a t ) : 1730 cm*1 ( l i t 1731 cm"x); nmr: 6 2 .1
( s ) superim posed on 1 .9 (m). E xact mass: c a lc d 152.1201; found 152.1204.
The i r d i f f e r e d from t h a t r e p o r te d f o r b ie y c lo [4 .3 .1 ]d e c a n -1 0 -o n e ( S a d t le r
*e8389).
R e ac tio n o f B ic y c lo [5 ,2 .l ld e c a n -1 0 -o n e ( 5J?) w ith 2 ,4 -d in itro p h e n y lh y d ra z in e .
Ketone ^ (O.O76 g, 0 .0005 m ole) was t r e a t e d w ith 2 ,4 -d in itro p h e n y lh y d ra -
z in e (0 .2 g ) d is s o lv e d in c o n c e n tra te d s u l f u r i c a c id (2 m l), w a te r (3 m l),
and m ethanol (5 m l) t o y ie ld a crude d e r iv a t iv e ( p r e c ip i t a t i o n o ccu rred
a f t e r 30 m in ), 0 . l 4 g (82$ ). Pure b ic y c lo [5 .2 .1 Jd e c a n -1 0 -o n e d l n i t r o -
phenylhydrazone ( 56) was o b ta in e d a f t e r r e c r y s t a l l i z a t i o n from e th a n o l a s
b r ig h t o range p l a t e s , mp 175- 176° ( l i t mp 176-177 .5° ) t *Ve ** 332.46
A dm ixture w ith an a u th e n tic sample o f t h e d e r iv a t iv e showed no m e lt
in g p o in t d e p re ss io n ; b o th sa n p le s p o sse ss i d e n t i c a l i r s p e c t r a l p ro p e r
t i e s ; i r (KBr); 33OO (w ), 3100 (w), l 6 l0 ( s ) , and 1330 cm- 1 ( s ) . E xact
m ass: c a lc d 332.1484; found 332.1488.
2 1 k
R eaction of exo-2 -C h lo ro b lc y c lo [5 .2 .lld e c a -3 .5 » 8 -tr ie n -1 0 -o n e (ph) v i t h S i l -
ve r A ceta te . Chloroketone (0.2U g, 0.0013 mole) was d isso lv ed in a c e t ic
a c id (5 ®l) co n ta in in g s i l v e r a c e ta te (0 . 1+3 g , 0.0026 mole) in a f la s k
wrapped v i th aluminum f o i l to exclude l ig h t . The r e a c t io n m ixture was
s t i r r e d a t 25° f o r 3 days, d i lu te d w ith e th e r (UO ml) and f i l t e r e d to
remove a l ig h t t a n p r e c ip i t a te . The p r e c ip i t a te was washed w ith two a d d i
t io n a l p o r t io n s o f e th e r (10 m l). The combined f i l t r a t e was washed v i th
w ater (*+x), s a tu ra te d sodium b ica rb o n a te (2 x ) , and sa tu ra te d b r in e . F i l
t r a t i o n through D rie r i t e and co n cen tra tio n o f th e f i l t r a t e y ie ld e d a yellow
l iq u id (0 .19 g ) . E vaporative d i s t i l l a t i o n (0 .075 nm) provided a yellow
l iq u id (O.16 ,g ) c o n ta in in g 10$ s t a r t i n g ch loroketone by g lc a n a ly s is .
The m ajor component o f th e m ixture (80$) by g lc was exo- 2-ace toxyb icyc lo -
[ 5 . 2 . l ] d e c a - 3 , 5, 8- t r i e n - 10-one (M+, o v e ra ll y ie ld « 1+7$) id e n t ic a l in
a l l re s p e c ts t o th e p rev io u s ly p repared acetoxyketone Ml. Acetoxyketone
M+ prepared in t h i s manner a ls o rea rran g ed t o endo- 6 - ( 018- 2 * -ac e to x y v in y l)-
c is -b ic y c lo [3 .3 .0 ]o c ta -3 ,7 -d ie n -2 -o n e ( 57) upon p re p a ra tiv e g lc as p re
v io u s ly d e sc rib e d .
Attempted W olff-K ishner R eduction o f B ic y c lo [h .2 .2 ]d e c a -2 ,1+.9 - t r ie n - 7 -
one ( l ) . Ketone 1 (0 .25 g> 0.0017 m ole), potassium hydroxide (O.75 g ) ,
and hydrazine h yd ra te (1 .5 ml) were re f lu x e d in e thy lene g ly co l (1+ ml)
(b a th tem per a t \ire = 200°) fo r 2 h r . The s t i r r e d m ixture was cooled an
a d d it io n a l 0 .5 h r , poured in to w ater (100 ml) and e x tra c te d w ith pentane
(1+ x 25 m l). The conibined pentane la y e r was f i l t e r e d through B r ie r i te and
concen tra ted t o y ie ld an o ff-w h ite s o l id (0 .13 g) which con ta ined two
h ig h ly v o la t i l e m a te r ia ls ( 5$) of sh o r t r e te n t io n tim e and a m a te r ia l ( 95$)
o f long r e te n t io n tim e by g lc a n a ly s is (column A).
115
Pure 2 ,3 - d ia z a t r ic y c lo [ 6 .3 .1 .0 4*11]d o d e c a -2 ,5 ,9 - tr ie n e (64^ o v e ra l l
y i e l d = b'J'fc) was c o l le c te d as a w hite s o l id hy p re p a ra t iv e g lc , mp 170- 172° .
A f r e s h SE-30 g lc column was n ecessa ry f o r c o n s is te n t g lc r e s u l t s ; i r
(m u ll) : 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 a t C - l) , 2 .6 (m,
3H, H a t C-7, - 8 , -1 1 ) , 2 .1 ( t , 2H, H a t C - l l , -1 2 ) , and 1 .8 ( s e p tu p le t ,
IK, H a t C -12); uv : X ^ lohexane 200 and 333 nm ( emax = 3 ,700 and 330).
E xact mass: c a lc d 160.1000; found 160.1003*
Anal. C alcd f o r CioHi2N2 : C, 74 .97 ; H, T .55* N, 17-48.
Found: C, 74 .79 ; H, 7 .7 2 ; N, 17 .57 .
R eac tio n o f B ic y c lo [4 .2 .2 ] d e c a - 2 ,4 ,9 - t r ien -7 -o n e ( l ) w ith H ydrazine.
Ketone 1 (0 .2 2 g , 0.0015 mole) and h yd raz ine h y d ra te (10 ml) were warmed
f o r 2 h r a t 75°. The m ix tu re was e x tra c te d w ith ch loroform (3 x ); th e
ch loroform la y e r s were f i l t e r e d th rough p o tassiu m carbonate and co n cen tra
t e d under reduced p re s s u re t o y ie ld b ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e
hydrazone ( 65 ) a s a y e llo w o i l (0 .23 St 96?>); i r (n e a t) ; 333° (m), 3200
(m), and 165O cm"1 (m); nmr: 6 5 .8 (m, 6h , H a t C-2, -3 , -4 , -5 , -9 , -1 0 ) ,
4 .7 5 (broad s , 2H, N-H, d isa p p ea rs 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: ca lcd 160.1000;
found 160. 1003 .
R eac tion o f B ic y c lo [4 .2 .2 ]d e c a -2 ,4 ,9 - t r ien -7 -o n e Hydrazone (65 ) w ith T osyl
C h lo ride . Hydrazone 6£ (0 .1 1 g, O.OOO69 mole) was added to to s y l c h lo r id e
(0 .1 4 g, 0 .00073 mole) i n d ry p y r id in e ( l ml) and th e m ixture was s t i r r e d
a t 25° fo r 9 hr* The r e a c t io n m ix tu re was quenched w ith w a ter (25 ml) and
e x tra c te d w ith m ethylene c h lo r id e (3 x ) . The combined o rg an ic la y e r s were
116
vashed v i th w ater ( ix ) , aqueous sodium 'bicarbonate ( lx ) , and sa tu ra te d
b r in e , f i l t e r e d through D r ie r i te and concen tra ted to y ie ld a brown o i l
(0 .18 g, 86$ ) . The o i l was c ry s ta l l iz e d from e thano l a f t e r charcoal de
c o lo r iz a t ion t o y ie ld m a te r ia l id e n t ic a l t o th e p rev io u sly prepared to s y l-
hydrazone 12 In i r and nmr s p e c tra l p ro p e r t ie s , mp 154-157°.
A t t e s t e d W olff-K ishner Reduction of B ic y d o [4 .2 .2 ]d e c a -2 ,4 ,9 - tr ie n -7 -o n e
Hydrazone ( 65.). Potassium t-b u to x id e (O.15 g , 0.0014 mole) was d isso lv ed
. i n dry d im ethy lsu lfox ide (1 .5 m l). Hydrazone 6£ (0 .15 g, 0,0009 mole) d i s
so lved in d ry d im ethy lsu lfox ide (3 .0 ml) was added dropwise over 5 min.
A fte r s t i r r i n g fo r 2 h r , th e r e a c t io n m ixture was quenched w ith pentane (JO
ml) and w ater (30 m l). The aqueous la y e r was th en washed w ith e th e r (30
ml) and th e combined organic la y e r was washed w ith sa tu ra te d b r in e , f i l t e r e d
through D r ie r i t e and concen tra ted t o y ie ld a ta n so lid (0 .08 g) which was
85$ p y razo lin e 64 by g lc a n a ly s is (o v e ra ll y ie ld 0 48$). Two o th er vo la
t i l e p roducts (combined y ie ld = 8$) were not id e n t i f ie d .
Attempted W olff-K ishner R eduction o f B icy c lo [4 .2 .2 ]d eca-2 ,4 ,9 - tr ie n -7 -o n e
