"Science, Faculty of"@en . "Chemistry, Department of"@en . "DSpace"@en . "UBCV"@en . "Haywood-Farmer, John S."@en . "2011-10-31T18:04:54Z"@en . "1965"@en . "Master of Science - MSc"@en . "University of British Columbia"@en . "The synthesis of exo-antl-tricyclo [3,2,1,02,4] octan-8-ol\r\n (V) and exo-anti-8-methoxy-tricyclo [3,2,1,02,4] octane (VI) was carried out by the cuprous chloride catalysed reaction of diazoraethane with anti-7-norbornenol (IV). The methyl ether\r\n(VI) was previously thought to be the endo isomer of (V). Methylene addition to the syn double bond of 7-norbornadienyl acetate (III) was accomplished using the above method to give a 5 to 1 mixture of exo-syn-tricyclo [3,2,1,02,4] oct-6-ene-8-\r\nacetate (VII) and endo-syn-tricyclo [3,2,1,02,4]\r\noct-6-ene-8-\r\nacetate (VIII). These two acetates were inseparable but the\r\ncorresponding alcohols exo-syn-tricyclo [3,2,1,02,4] oct-6-ene-8-ol (X) and endo-syn-tricyclo\r\n[3,2,1,02,4] \r\noct-6-ene-8-ol (XI),\r\nformed by reduction of the acetate mixture with lithium aluminum\r\nhydride, could be separated by gas-liquid partition chromatography. The stereochemistry of these two products was determined by the multiplicity and by the chemical shift of the olefinic proton signals in their proton nuclear magnetic resonance spectra. Catalytic reduction of these two\r\nalcohols gave exo-syn-tricyclo [3,2,1,02,4] octan-8-ol (XIII)\r\nand endo-syn-trlcyclo [3,2,1,02,4]\r\noctan-8-ol (XIV). From\r\nthe diazomethane-7-norbornadienyl acetate reaction a diadduct\r\nacetate, tetracyclo [3,3,1,02,4,06,8]nonan-9-acetate (IX), was\r\nalso obtained which reduced to the alcohol tetracyclo [3,3,1,02,4,06,8]\r\nnonan-9-ol (XII). The stereochemistry of these diadducts\r\nwas not determined. Acetolysis studies on the p-bromobenzene-\r\nsulfonyl (brosylate) derivative of exo-anti-tricyclo [3,2,1,02,4]octan-8-ol (V) at 200\u00B0 indicate that the reaction proceeds by formation of a carbonium ion at C8, which then rearranges, destroying the cyclopropyl group. Although unchanged (V) could be obtained by lithium aluminum hydride reduction of about 80% solvolysed brosylate at 200\u00B0, none of the products of complete solvolysis could be identified."@en . "https://circle.library.ubc.ca/rest/handle/2429/38457?expand=metadata"@en . "M E T H Y L E N E A D D I T I O N TO SOME 7 - N O R B O R N A D I E N Y L D E R I V A T I V E S b y JOHN S. HAYWOOD-FARMER B . S c . H o n o r s , T h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , 1963 A T H E S I S S U B M I T T E D I N P A R T I A L F U L F I L M E N T OF THE R E Q U I R E M E N T S FOR THE D E G R E E OF MASTER OF S C I E N C E i n t h e D e p a r t m e n t o f C h e m i s t r y We a c c e p t t h i s t h e s i s a s c o n f o r m i n g t o t h e r e q u i r e d s t a n d a r d T H E U N I V E R S I T Y OF B R I T I S H COLUMBIA A p r i l , 1965 I n p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f t h e r e q u i r e m e n t s f o r an a d v a n c e d d e g r e e a t t h e U n i v e r s i t y o f \u00E2\u0080\u00A2 B r i t i s h C o l u m b i a , I a g r e e t h a t t h e L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and s t u d y , I f u r t h e r a g r e e t h a t p e r -m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y p u r p o s e s may be g r a n t e d by t h e Head o f my D e p a r t m e n t o r by h i s r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t c o p y i n g o r p u b l i -c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l n o t be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n * D e p a r t m e n t o f Chemistry The U n i v e r s i t y o f B r i t i s h C o l u m b i a , V a n c o u v e r 8, C a n a d a ABSTRACT The sy n t h e s i s of e x o - a n t l - t r i c y c l o 3,2,1,0^'^ o c t a n - 8 - o l 3,2,1,0 2,4 octane (VI), was (V) and e x o - a n t i - 8 - m e t h o x y - t r i c y c l o c a r r i e d out by the cuprous c h l o r i d e c a t a l y s e d r e a c t i o n of diazoraethane w i t h a n t i - 7 - n o r b o r n e n o l ( I V ) . The methyl ether (VI) was p r e v i o u s l y thought t o be the endo isomer of (V). Methylene a d d i t i o n t o the ayn double bond of 7-norbornadienyl acetate ( I I I ) was accomplished using the above method to give a 5 to 1 mixture of e x o - s y n - t r i c y c l o [ 3 ,2, 1,0^ * 4 o c t - 6 - e n e - 8 -acetate (VII) and e n d o - s y n - t r i c y c l o [ 3 , 2 , 1 , 0 ^ * ^ o c t - 6 - e n e - 8 -acetate ( V I I I ) . These two acetate s were inseparable but the corresponding alcohols exo-syn-tricyclo 3,2,1,0 2,4 8 - 0 I (X) and e n d o - s y n - t r i c y c l o 3,2,1,0 2,4 oct - 6-ene-o c t - 6 - e n e - 8 - o l ( X I ) , formed by r e d u c t i o n of the acetate mixture w i t h l i t h i u m alum-inum hydride, could be separated by g a s - l i q u i d p a r t i t i o n chromatography. The stereochemistry of these two products was determined by the m u l t i p l i c i t y and by the chemical s h i f t of the o l e f i n i c proton s i g n a l s i n t h e i r proton nuclear mag-n e t i c resonance s p e c t r a . C a t a l y t i c r e d u c t i o n of these two a l c o h o l s gave e x o - s y n - t r i c y c l o and e n d o - s y n - t r l c y c l o [ 3 , 2 , 1 , 0 ' 3,2,1,0 2,4 o c t a n - 8 - o l ( X I I I ) 2,4 oc'tan-8-ol (XIV). From the diazomethane - 7-norbornadienyl acetate r e a c t i o n a diadduct a c e t a t e , t e t r a c y c l o 3,3,1,0 2' 4,0 6' 8 nonan - 9-acetate ( I X ) , was a l s o obtained which reduced to the a l c o h o l t e t r a c y c l o 0 6 , 8 3,3,1,0 2 , nonan - 9-ol ( X I I ) . The stereochemistry of these diadducts was not determined. A c e t o l y s i s s t u d i e s on the p_-bromobenzene-s u l f o n y l (brosylate) derivative of e x o - a n t i - t r i c y c l o |3,2,1,0 octan-8-ol (V) at 200\u00C2\u00B0 indicate that the reaction proceeds by formation of a carbonium ion at 0 3 , which then rearranges,^ destroying the cyclopropyl group. Although unchanged (V) could be obtained by l i t h i u m aluminum hydride reduction of about 80$ solvolysed brosylate at 200\u00C2\u00B0, none of the products of complete s o l v o l y s i s could be i d e n t i f i e d . II III C u 2 C l 2 IV V VI rOAc K-OAC i n VII VIII LiAlH, RTOH XI H 2 / P t r O H A y H o / P t H XIII XIV rrOH TO = -Q-SOjCl pyridine fr-OBs t6 v XV \u00E2\u0080\u00A2? ACKNOWLEDGEMENT I should l i k e to express my sincere thanks and apprecia-t i o n to Dr. R. E. Pincock for his f r i e n d l y , u n s e l f i s h help and encouragement throughout t h i s research. The counsel of Mr. W. B. Scott and Mrs. J. I. Wells i s likewise g r a t e f u l l y acknowledged. T A B L E OF CONTENTS I N T R O D U C T I O N A . H i s t o r i c a l B. S y n t h e t i c R o u t e s E X P E R I M E N T A L A . G e n e r a l B. S y n t h e t i c C. P r o d u c t S t u d i e s SUMMARY OP E X P E R I M E N T A L R E S U L T S A . S y n t h e t i c B. S o l v o l y s i s S t u d i e s D I S C U S S I O N A . S y n t h e s i s B. S t r u c t u r a l P r o o f C. S o l v o l y s i s S t u d i e s D. C o n c l u s i o n E . S u g g e s t i o n s f o r F u r t h e r R e s e a r c h R E F E R E N C E S ; I. INTRODUCTION A. HISTORICAL In recent years the synthesis and chemistry of cyclo-propane compounds has been of considerable i n t e r e s t because of the novelty associated with, and the s t r a i n inherent i n such a small r i n g . Coulson and Moffit (1) have shown by molecular o r b i t a l c a l c u l a t i o n s that the o r b i t a l s forming the carbon-carbon bonds i n cyclopropanes are not at an angle of 60\u00C2\u00B0 as expected for an e q u i l a t e r a l t r i a n g l e but are spread to 106\u00C2\u00B0. Thus, although the r i n g i s necessarily planar, the annular bonds are bent (see figure 1) and the overlap i s not true sp^. Because of the poor overlap inherent i n such a bent-bond model, some cf-electron d e l o c a l i s a t i o n occurs imparting a c e r t a i n amount of added s t a b i l i t y to the r i n g . This d e l o c a l i s a t i o n i s oriented i n the annular plane, not i n two planes p a r a l l e l to the r i n g as i n benzene. The properties of cyclopropane derivatives are consistent with the idea of a p a r t i a l l y delocalised structure (2,3). In conjugated double bond systems i t i s well known that there i s a transmission of e l e c t r i c a l e f f e c t s along the chain. I t has figure 1 - 2 -a l s o been found that cyclopropyl groups can a l s o support d e l o c a l i s a t i o n , being weaker i n t h i s respect than ethylene groups but stronger than a saturated dimethylene group (2,3). U l t r a v i o l e t spectroscopy studies on the conjugation of cyclo-propyl groups with carbonyl compounds (4), aromatic systems (5), and o l e f i n s (6) a l l show bathochromic s h i f t s i n d i c a t i n g that d e l o c a l i s a t i o n occurs. Infra-red spectroscopy (I.R.) (7) and nuclear magnetic resonance (N.M.R.) studies (8) also support t h i s idea. Chemical evidence for conjugation of cyclopropyl groups with carbonyl groups (9), with o l e f i n s (10) and with carbonium ion intermediates (10, 11) also e x i s t s . In order to explain the behaviour of some chemical reactions, to'instein (12) introduced the concept of homo-conjugation. I t was found that some norbornenyl derivatives underwent s o l v o l y s i s reactions In a ster e o s p e c i f i c manner at a much enhanced rate to those for the corresponding saturated analogues (13, 14). The homoconjugation was viewed as some in t e r a c t i o n between the TT -electrons of the unsaturated center and the developing carbonium ion from which i t was separated by a methylene group. This 1,3- i n t e r a c t i o n was represented i n a sim i l a r manner to that for the more f a m i l i a r case of a l l y l i c resonance (figure 2a). \u00C2\u00A9 \u00C2\u00A9 \u00C2\u00A9 a b figure 2 - 3 -Woodward and WInstein (14) found anti-7-norbornenyl tosylate to be 1 0 ^ times more reactive towards s o l v o l y s i s than 7-norbornyl tosylate. Complete retention of configura-t i o n was reported (14). Roberts (15) reported si m i l a r r e s u l t s for the corresponding chlorides. In order to explain the vast difference i n rate between the saturated and unsaturated compounds, Winstein (14) formu-lated a bridged or \"non-classical\" ion (figure 2b). The geometry of anti-7-norbornenyl cation i s very favorable f o r d e l o c a l i s a t i o n of the T f -electrons of the double bond with the vacant p - o r b i t a l r e s u l t i n g from formation of the carbonium ion at Cy. Brown (16), on the other hand, fe e l s that although some in t e r a c t i o n does occur between the double bond and the car-bonium ion, i t i s i n the form of c l a s s i c a l ion resonance structures (figure 3): \u00C2\u00A9 figure 3 Considering the many analogous properties of cyclopropyl groups and o l e f i n s , Pincock and Wells (17) decided to study the p o s s i b i l i t y of p a r t i c i p i t a t i o n of cyclopropyl groups with - 4 -forming carbonium\u00E2\u0080\u00A2ion intermediates by studying the s o l v o l y s i s of cyclopropane substituted 7-norbornyl der i v a t i v e s . The isomer they examined was _exo-anti-tricyclo {3,2,1,0^'^ octan-8-brosylate (figure 4a). Because the o r b i t a l s available for such p a r t i c i p a t i o n are directed away from the reactive center by the arrangement of the cyclopropane r i n g , l i t t l e change was expected i n s o l v o l y s i s rate from that of the saturated 7-norbornyl brosylate (figure 4b). This was i n fact the observed case (17b). The corresponding endo isomer (figure 4c) on the other hand,has the o r b i t a l s of the r i n g directed toward the reactive center and i f d e l o c a l i s a t i o n does occur, one would expect a rate s i m i l a r to that for antl-7-norbornenyl brosylate (figure 4d). r O B s a b c d figure 4 ! The purpose of t h i s work was to investigate possible routes of synthesis of endo-antl-tricyclo J3,2,1,0^*^ octan-8-brosylate (figure 4c) and i f possible to study i t s rate of s o l v o l y s i s . B. SYNTHETIC ROUTES The synthesis of cyclopropane rings as parts of l a r g e r r i n g systems has been c a r r i e d out i n three general ways. The Diels-Alder reaction between suitable c y c l i c dienes - 5 -using cyclopropene as the dieneophile gives good y i e l d s of the corresponding adduct (18) (figure 5). O + A \u00E2\u0080\u0094 /t> figure 5 Such reactions usually give the endo adduct by k i n e t i c control (19) although the exo isomer Is the more stable and can often be formed from the endo one by thermal Isomerisation. This has been observed i n the cases of cyclopentadiene dimer (20) and of the adduct of cyclopentadiene with maleic anhydride (21). Carbenes w i l l add to o l e f i n s to give the corresponding cyclopropyl derivative (22). Dihalocarbenes can be prepared by the reaction of haloform with a strong base (22) or i n better y i e l d s by reacting ethyl trihaloacetate with a strong base (23). The r e s u l t i n g gem-dihalocyclopropanes however are unstable and rearrange to the rin g expanded product quite e a s i l y (24). Methylene halides also react with strong base giving the monohalocarbene which forms monohalocyclopropanes by reacting with ol e f i n s (25). The procedure of Simmons and Smith (26) also uses a methylene halide, s p e c i f i c a l l y methylene iodide, as the source of carbene but zinc-copper couple i s employed as a generating agent and r e s u l t s i n unsubstituted carbene forma-t i o n . The methylene iodide may be substituted by one or two - 6 -a l k y l or a r y l groups g i v i n g r i s e t o the correspondingly sub-s t i t u t e d c'yclopropanes. This r e a c t i o n i s thought t o proceed through a complex between the methylene i o d i d e and z i n c (26d). In 1963, von E. Doering and Roth (27) reporte d t h a t s cyclopropanes can be formed by r e a c t i n g diazomethane gas w i t h o l e f i n s i n the presence of cuprous c h l o r i d e . The r e a c t i o n I s thought to proceed through a t t a c k on the double bond by a carbene-copper complex (28). This complex i s formed by bonding of the n u c l e o p h i l i c carbon atom of dia z o -methane to the vacant o r b i t a l s of copper. Simultaneous or successive s p l i t t i n g o f f of n i t r o g e n occurs t o leave the carbene-copper complex. As w i t h the Simmons-Smith r e a c t i o n , s u b s t i t u t e d d e r i v a t i v e s can be made by using the appropriate diazomethane. This reagent has been found t o be much more e f f e c t i v e than the Simmons-Smith reagent w i t h r e s p e c t to a d d i t i o n to norbornenes and norbornadienes (17b) and has been found t o be a c t i v e enough to add to aromatic systems (27). The r o l e played by the cuprous c h l o r i d e c a t a l y s t i s one of d e a c t i v a t i o n since i n the presence of l i g h t , various i n s e r t i o n r e a c t i o n s a l s o occur a t -75\u00C2\u00B0 when diazomethane i t s e l f i s used (29). The danger a s s o c i a t e d w i t h the hand-l i n g of diazomethane (30) has been reduced to a minimal l e v e l by a procedure developed by Pincock and Wells (17b). The D i e l s - A l d e r r e a c t i o n which looks the most promising of a l l on a stereochemical b a s i s i s not a p p l i c a b l e here because no s u i t a b l e oxygen s u b s t i t u t e d cyclopentadiene i s a v a i l a b l e , and because cyclopropene i s d i f f i c u l t t o prepare and t o handle. The Simmons-Smith procedure i s not too - 7 -applicable to the norbornene and norbornadiene series (17). In view of these facts i t was decided to investigate the diazomethane addition to 7-norbornadienyl acetate and a n t i -7-norbornenol (figure 6) as possible routes to the synthesis of endo-anti-tricyclo 3,2,l,02\u00C2\u00BB4]'octan-8-ol (figure 4c). r O A c figure 6 - 8 -- 9 -I I . EXPERIMENTAL A. GENERAL I n f r a - r e d spectra (I.R.) were taken on a Perkin-Elmer 137 I n f r a c o r d spectrophotometer w i t h frequencies l i s t e d i n cm\"^; w = weak, m = medium, s = strong. Spectra were obtained on neat l i q u i d samples or on n u j o l mulls of s o l i d samples using sodium c h l o r i d e o p t i c s i n both cases. Nuclear magnetic resonance spectra (N.M.R.) were obtained on a V a r i a n A-60 spectrometer w i t h resonance frequencies given i n T u n i t s , based on tetramethyl s i l a n e at 10T , i n carbon t e t r a c h l o r i d e s o l u t i o n ; s = broad s i n g l e t or unresolved m u l t i p l e t , m = m u l t i p l e t only p a r t i a l l y r e s o l v e d , 2 = doublet e t c . A l l peaks i n t e g r a t e d f o r the c o r r e c t number of protons unless otherwise s t a t e d . The resonance p o s i t i o n s of the hydroxyl protons were unambiguously assigned by observ-i n g t h e i r s h i f t upon a d d i t i o n o f p y r i d i n e to the samples. Microanalyses were done by A. Bernhardt of Mulheim and by C. Jenkins of t h i s department. G a s - l i q u i d chromatography (V.P.C.) was done on three columns; a f i v e foot 20$ Apiezon J on 60/80 mesh f i r e b r i c k column, a f i v e foot 20$ l,2,3-Tris(2-cyanoethoxy)propane on . 45/60 mesh chromosorb P (T.C.E.P.) column, and a f i v e foot 25$ Carbowax 20M ( a c i d washed) on 60/80 mesh chromosorb W column using helium as the c a r r i e r gas at a flow r a t e of 42 ml. per min. (48 p . s . i . ) . A l l chemicals used were of reagent grade and used without f u r t h e r p u r i f i c a t i o n unless otherwise s t a t e d . - 10 -T h i n - l a y e r c h r o m a t o g r a p h y ( T . L . C . ) w a s d o n e o n p l a t e s o f B.D.H. s i l i c a g e l G ( f o r T . L . C , ) a n d w e r e made b y t h e m e t h o d o f B i s h o p a n d T a t e ( 3 D . C o l u m n c h r o m a t o g r a p h y w a s d o n e o n B.D.H. c h r o m a t o g r a p h i c s i l i c a g e l . B. S Y N T H E T I C 1. 7 - t - B u t o x y n o r b o r n a d i e n e ( I I ) (32): T o a s t i r r e d r e f l u x i n g m i x t u r e o f 149 g . (1.62 m o l e s ) o f n o r b o r n a d i e n e ( I ) ( M a t h e s o n , C o l e m a n a n d B e l l , P r a c t i c a l g r a d e ) a n d 0.325 g . (0.00226 m o l e s ) o f c u p r o u s b r o m i d e i n 500 m l . o f b e n z e n e i n a t h r e e - n e c k e d , 2 1. f l a s k u n d e r n i t r o -g e n , w a s a d d e d 122.5 g . (0 .63 m o l e s ) o f t - b u t y l p e r b e n z o a t e ( M a t h e s o n , C o l e m a n a n d B e l l , P r a c t i c a l g r a d e ) i n 100 m l . o f b e n z e n e o v e r a b o u t o n e h o u r . T h i s a d d i t i o n w a s a c c o m p a n i e d b y f o r m a t i o n o f a d e e p g r e e n c o l o r a t i o n o f t h e b e n z e n e s o l u -t i o n . A f t e r a f u r t h e r h o u r o f r e f l u x , t h e s o l u t i o n w a s c o o l e d t o r o o m t e m p e r a t u r e , t r a n s f e r r e d t o a s e p a r a t o r y f u n n e l a n d e x t r a c t e d w i t h 10$ a q u e o u s s o d i u m c a r b o n a t e s o l u t i o n u n t i l a l l t h e b e n z o i c a c i d h a d b e e n r e m o v e d . T h e r e s u l t i n g y e l l o w b e n z e n e s o l u t i o n w a s w a s h e d w i t h w a t e r a n d s a t u r a t e d a q u e o u s s o d i u m c h l o r i d e s o l u t i o n a n d d r i e d o v e r a n h y d r o u s m a g n e s i u m s u l f a t e . A f t e r f i l t e r i n g , m o s t o f t h e b e n z e n e w a s r e m o v e d b y r o t a r y e v a p o r a t i o n a t a b o u t 35\u00C2\u00B0. 7 - ^ - B u t o x y n o r b o r n a d i e n e ( I I ) w a s d i s t i l l e d f r o m t h e r e s u l t i n g v i s c o u s b r o w n o i l ; b.pt., 64-67\u00C2\u00B0/l2 mm., ( r e p o r t e d , 70-72\u00C2\u00B0/l4 mm. ( 3 2 ) ) . Y i e l d 25.5 g . (25$). I . R . : 2950 ( s ) , 1540 ( w ) , 1390 ( m ) , 1360 ( s ) , 1320 ( m ) , 1190 ( s ) , 1105 ( s ) , 730 ( s ) . N.M.R.: o l e f i n i c 3.49 (3), 3.62 ( m ) ; b r i d g e 6.32 ( s ) ; - 11 -bridgehead 6 .73 (m); t-butyl 8 .93 (1). 2. 7-Norbornadienyl acetate (III) ( 3 2 ) : An ice-cooled solution of 20 g. (0.122 moles) of 7-t-butoxynorbornadiene (II) i n 40 ml. of acetic anhydride and 200 ml. of g l a c i a l acetic acid was added to 27 g. of 70$ perchloric acid which had previously been cooled to 0\u00C2\u00B0. After exactly one minute the r e s u l t i n g deep red so l u t i o n was poured into a mixture of about 650 g. of water and ice i n a separatory funnel. After warming to room temperature to melt the remaining i c e , the orange solution, from which had separated an orange liquid,was extracted with four 100 ml. portions of dichloromethane. The organic solution was separated, washed with water, saturated aqueous sodium bicar -bonate so l u t i o n , water, and f i n a l l y saturated aqueous sodium chloride solution. After drying over anhydrous magnesium sulfate the die h i or ome thane was taken off by rotary evapora-t i o n at about 35\u00C2\u00B0 and the r e s u l t i n g deep orange, viscous o i l d i s t i l l e d to give 15.1 g. (82.5$) of 7-norbornadienyl acetate ( I I I ) ; b.pt. 76-79\u00C2\u00B0/H mm., (reported: 65\u00C2\u00B0/8 mm. ( 3 2 ) ) : I.R.: 2950 ( s ) , 1730 (s), 1540 (w), 1370 (m), 1320 (m), 1245 (s), 1040 (s), 910 (m), 835 (m), 735 ( s ) , 680 (m). N.M.R.: o l e f i n i c 3.35 ( 3 ) , 3.53 (m); bridge 5.55 (s); bridgehead 6.46 (m); acetate 8.13 (1). 3. anti-7-Norbornenol (IV) (32): 7-Norbornadienyl acetate ( I I I ) , 5.0 g. (0.033 moles), i n 100 ml. of anhydrous d i e t h y l ether was added at room - 12 -temperature to a magnetically s t i r r e d suspension of 2.0 g. (0.053 moles) of f i n e l y divided l i t h i u m aluminum hydride i n 100 ml. of anhydrous d i e t h y l ether i n a 500 ml. three-necked f l a s k f i t t e d with a condenser and an a d d i t i o n funnel over a period of about f i f t e e n minutes. After a further hour of s t i r r i n g at room temperature, water and ice were slowly added to hydrolyse any excess l i t h i u m aluminum hydride. The r e s u l t i n g suspended white aluminum s a l t s were dissolved by the addition of 10$ aqueous s u l f u r i c a c i d . The ether layer and washings were washed with 10$ aqueous sodium car-bonate solution, water, and saturated aqueous sodium chloride solution, and dried over anhydrous magnesium s u l f a t e . The ether was evaporated to give 3.2 g. (87.5$) of a yellowish semi-crystalline material. P u r i f i c a t i o n by V.P.C. on the Apiezon J column at 150\u00C2\u00B0 gave pure antl-7-norbornenol (IV); m.pt., 115-116\u00C2\u00B0, (reported: 117-118\u00C2\u00B0 (32)). No syn isomer or 7-norbornadienol i s formed i n t h i s r e a c t i o n (32). I.E.: 3300 (s), 2950 (s), 1630 (w), 1570 (w), 1330 (m), 1 1120 (s), 1070 (s), 870 (m), 710 ( s ) . N.M.R.: o l e f i n i c 4.10 (3); hydroxyl 6.42 (1); bridge 6.55 (s); bridgehead 7.54 (m); endo/exo 8.22 (m), 9.07 (m). 4. Reactions of o l e f i n s with diazomethane (17): a) General procedure (17b): Diazomethane was generated from N-methyl-N-nitrosourea which was prepared by the method of Arndt (33) i n 60$ y i e l d . The generator consisted of a 250 ml., three-necked, ice-cooled - 13 -f l a s k containing 50 ml. of a magnetically s t i r r e d 50$ aqueous potassium hydroxide solution and 100 ml. of di e t h y l ether. Addition of N-methyl-N-nitrosourea i n approximately 1 g. l o t s generated diazomethane which dissolved i n the ether la y e r . The diazomethane was carr i e d to the reaction f l a s k through a drying tube of potassium hydroxide p e l l e t s by a continuous stream of dry nitrogen which bubbled through the ether layer i n the generator f l a s k . The r e a c t i o n vessel consisted of a 100 ml. three-necked, ice-cooled f l a s k containing a magnetically s t i r r e d s o l u t i o n of o l e f i n i n 50 ml. of anhydrous d i e t h y l ether with about 0.15 moles of cuprous chloride as c a t a l y s t , through which the nitrogen stream passed. The outlet was through a water-cooled condenser f i t t e d with a drying tube. The ether layers i n both f l a s k s were maintained by addition of solvent when required. The reac t i o n was followed by V.P.C. of the ether solut i o n and was continued f o r several hours u n t i l the o l e f i n was consumed. The reaction mixtures were worked up by simple f i l t r a t i o n of the cat a l y s t followed by evaporation of the solvent. During the reactions i t was noticed that the catalyst changed from green to a dark metallic reddish brown but returned to i t s normal color when the diazomethane generation was stopped. Rubber stoppers were used i n a l l connections because of the danger of explosions with diazo-methane on ground-glass surfaces (30). The danger of explosions and poisoning was also minimized by the steady nitrogen stream which kept the concentration of diazomethane quite low. - 14 -b) Reaction with anti-7-norbornenol (IV): preparation of exo-anti-tricyc1o 3,2,1,0 2' 4 octan-8-ol (V) (17b) Diazomethane was reacted with 10.5 g. (0.0955 moles) of anti-7-norbornenol (IV) i n the presence of 1.2 g. of cuprous chloride as catalyst for 12 hours. The progress of the reac-t i o n was followed by V.P.C. on the Apiezon J column at 150\u00C2\u00B0. F i l t r a t i o n and evaporation of the ether solution gave a greenish o i l from which two products were Isolated by V.P.C. on the T.C.E.P. column at 130\u00C2\u00B0, the major one of which was r 2,. shown to be i d e n t i c a l to authentic exo-anti-trlcyclo13,2,1,0 octan-8-ol (V) by comparison of I.R. and N.M.R. spectra and by mixed melting point with an authentic samples of the alcohol (17). The minor product was further p u r i f i e d by V.P.C. on T.C.E.P. at 103\u00C2\u00B0 and was shown by the I.R..-and N.M.R. spectra to be a methyl ether containing a cyclopropyl group. This compound was l a t e r confirmed to be exo-antl-8-methoxy-tricyclo ~ 2 4~ 3,2,1,0 ' octane (VI), (see section 7 below). Previous workers (17) had thought that t h i s compound was the endo isomer of (V). The o r i g i n a l greenish o i l was seeded with an authentic sample of the alcohol (V) and a f t e r standing for twenty-four hours at 0\u00C2\u00B0 afforded 4.3 g. (36.4$) of greenish c r y s t a l s . R e c r y s t a l l i s a t i o n was effected from petroleum ether (b.pt., 65-110\u00C2\u00B0) giving white c r y s t a l s of the alcohol; m.pt., 68.5-70\u00C2\u00B0, (reported: 75-76\u00C2\u00B0 (17b)). Some of the alcohol remained In the mother liqu o r but no attempt was made to i s o l a t e i t . - 15 -The t o t a l y i e l d was estimated from a very complex V.P.C. trace to be about 9 0 $ with the main impurities being s t a r t i n g alcohol (IV) and methyl ether (VI). Wo attempt was made to characterise other products. ' I.R.: 3 4 0 0 (s), 1 4 5 0 (w), 1260 (m), 1 1 3 0 (s), 1 0 9 0 ( s ) , 1040 (s), 1 0 2 5 (m), 1000 (m), 955 (m), 810 (m), 740 (m). N.M.R.: hydroxyl 7.09 (1); bridge 6 . 4 6 (s); bridgehead 7.95 (s); endo/exo 8.28 (m), 8.71 (m); cyclopropyl 9.29 (m). c) Reaction with 7-norbornadienyl acetate ( I I I ) : r 2 41 i ) preparation of exo-syn-tricyclo 3,2,1,0 ' oct - 6-ene-8-acetate (VII), endo-syn-tricyclo J 3,2,1,0 2 \u00C2\u00BB 4 oct - 6-ene-8-acetate (VIII), and tetracyclo 3 , 3 , 1 , 0 2 , 4 , 0 6 * 8 nonan-8-acetate (IX): 7-Norbornadienyl acetate (III) 3 . 6 g. (0.024 moles), and 0.4 g. of cuprous chloride c a t a l y s t were reacted with diazomethane for 9 hours using a T.C.E.P. column at 130\u00C2\u00B0 to monitor the r e a c t i o n . From the r e s u l t i n g green o i l (4.3 g.) obtained by f i l t r a t i o n and evaporation of the ether solution was i s o l a t e d by V.P.C. on the T.C.S.P. column at 130\u00C2\u00B0 a non-separable mixture of (VII) and (VIII) (retention time twenty-seven minutes), and pure (IX) (retention time s i x t y minutes). The V.P.C. trace on T.C.E.P. at 1 3 0 \u00C2\u00B0 showed that at le a s t two components were present i n the mixture of (VII) and (VIII) but although other conditions were t r i e d none was found that would separate them s u f f i c i e n t l y f o r c o l l e c t i o n . - 16 -N.M.R. showed that a 5 to 1 mixture of (VII) to (VIII) was present. I.R. (on mixture): 3100 (w) , 3000 (m), 1740 (s), 1600 (w), 1550 (w), 1440 (w), 1360 (m), 1240 (s), 1040 (s), 900 (m), 850 (w), 780 (m), 720 (m), 690 (m). N.M.R. (VII): o l e f i n i c 3.67 (3); bridge 6.05 ( a ) ; bridgehead 7.11 (s); acetate 8.11 ( l ) ; cyclopropyl 9.0 (m). N.M.R. (VIII): o l e f i n i c 4.35 (3); bridge 5.58 (s); bridge-head 7.11 (s); acetate 8.11 (1); cyclopropyl 9.0 (m). Analysis (on mixture): calculated f o r C i o H12\u00C2\u00B02 : c = 73 . 15 , H = 7.37 found : C = 73.15, H = 7.39. The l i q u i d acetate (IX) was determined to be pure by V.P.C. on T.C.E.P. at 130\u00C2\u00B0 but i s of unknown stereochemistry. I.R.: 3000 (m), 2950 (m), 1740 (s ) , 1450 (w), 1420 (w), 1360 (m), 1320 (w), 1240 (s ) , 1220 (m), 1170 (w), 1100 (m), 1070 (m), 1040 (m), 980 (m),910 (m), 860 1 (w), 820 (w), 790 (m), 770 (w), 710 (m). N.M.R.: bridge 5.90 (s); bridgehead 7.59 (s); acetate 8.12 (1); cyclopropyl 8.89 (m) (six protons), 9.68 (m) (two protons); other 8.5 (m) (one proton). Analysis: calculated f o r C n R x ^ : C = 74.30, H = 7.92 found : C = 73.57, H = 7.92. - 17 -3,2,1,0 2' 4 i i ) preparation of exo-syn-tricyclo 8-ol' y(X), endo-syn-tricyclo [3,2,1,O 2' 4 oct-6-ene-oct-6-ene-8-ol (XI), and tetr a c y c l o [ 3 , 3 , 1 , 0 2 \u00C2\u00BB 4 , 0 6 , 8 nonan-9-ol (XII): 7^Norbornadienyl acetate (III), 10.5 g. (0.07 moles), and 1.2 g. of cuprous chloride c a t a l y s t were reacted with diazo-methane for 12 hours as given above, the catalyst f i l t e r e d o f f , and the ether s o l u t i o n slowly added at room temperature to 6.0 g. (0.159 moles) of f i n e l y divided l i t h i u m aluminum hydride suspended i n 100 ml. of magnetically s t i r r e d anhy-drous d i e t h y l ether contained i n a 250 ml. three-necked f l a s k f i t t e d with a condenser and an addition funnel. A f t e r the addition was complete, the reaction mixture was s t i r r e d f o r an a d d i t i o n a l hour at room temperature. Water and ice were then added to hydrolyse any remaining lithiu m aluminum hydride. The r e s u l t i n g white suspension of aluminum s a l t s was separated i n a separatory funnel and the ether solution washed with water, and saturated aqueous sodium chloride solu-t i o n , and dried over anhydrous magnesium s u l f a t e . Evaporation of the ether gave 7.4 g. (86$ based on addition of one mole of diazomethane) of a cle a r , c o l o r l e s s o i l . 2.0 g. of t h i s o i l was separated by column chromatography on 175 g. of s i l i c a gel using as solvent a 2 to 1 mixture of petroleum ether (b.pt. 30-60\u00C2\u00B0C.) to d i e t h y l ether, both of which were dried and d i s t i l l e d by standard methods (34) before use. The column separation, which was monitored by T.L.C. using the same solvent system, gave three f r a c t i o n s . - 18 -The f i r s t , R f 0 . 5 2 , was separated by V.P.C. on T.C.E.P. at 130\u00C2\u00B0 into two components. The more v o l a t i l e of these two (retention time twenty-five minutes) was i d e n t i f i e d as alc o -hol (X), m.pt. 33-34\u00C2\u00B0 (sealed tube). I.R.: 3300 (s), 3050 (w), 3000 (w), 1650 (w), 1080 (s), 1010 (w), 940 (w), 875 (w), 830 (m), 770 (m), 720 (m), 685 (s). N.M.R.: o l e f i n i c 3.62 (3); hydroxyl 5.95 (1); bridge 6.68 (s); bridgehead 7.18 (s); cyclopropyl 8.9 (m). Analysis: calculated for CgH.^0: C = 78.68, H = 8 . 2 5 , 0 = 13.10 found : C = 78.39, H = 8.38, 0 = 13.22 The other component of R f 0 .52 was i d e n t i f i e d as alcohol (XII) (retention time sixty-three minutes) of unknown stereo-chemistry, m.pt. 61-63\u00C2\u00B0 (sealed tube). I.R.: 3200 ( s ) , 2900 (s), 1100 (s), 1040 (s), 1030 (m), 970 (s), 925 (m), 855 (w), 805 (m), 785 (s), 750 (w), 690 (s). N.M.R.: hydroxyl 6.33 ( D ; bridge 6.67 (m); bridgehead 1 7.63 (s); cyclopropyl 8.80 (m) (six protons), 9.60 (m) (two protons); other 8.03 (m) (one proton). Analysis: calculated for CqH 1 20: C = 79.37, H = 8.88 found : C = 79.03, H = 9.09. The appearance of the extraneous peaks i n the N.M.R. spectra of both acetate (IX) and alcohol (XII) may be due to a second isomer. Formation of the exo and endo isomers (X) and (XI) indicates that at least two isomers should be - 19 -formed by addition of another methylene group and the cyclo-propyl protons of the smaller isomer may resonate at a s l i g h t l y lower f i e l d . The second f r a c t i o n , Rf 0.39, was further p u r i f i e d by V.P . C . on T . C . E . P . at 130\u00C2\u00B0 and was unequivocally shown by I.R. comparison with that of an authentic sample of the alco-hol (32) to be 7-norbornenol (IV) a r i s i n g from reduction of unreacted 7-norbornadienyl acetate ( I I I ) . M.pt. 116.5 - 117\u00C2\u00B0C. The t h i r d f r a c t i o n , R f 0.29, was also p u r i f i e d by V.P . C . on the T . C . E . P . column at 130\u00C2\u00B0 and was i d e n t i f i e d as alcohol (XI), m.pt. 60-62\u00C2\u00B0 (sealed tube). I.R.: 3350 (s), 3050 (w), 29OQ (s), 1600 (w), 1220 (s), 1070 (s), 1010 (m), 960 (ra), 920 (m), 870 (s), 790 (s), 755 (s), 730 (s), 720 ( s ) . N.M.R.: o l e f i n i c 4.33 (3); bridge 6.2 (s); hydroxyl 7.12 (m); bridgehead 7.42 (s); cyclopropyl 8.58 (m) (two protons), 9.3 (m) (two protons). Analysis: calculated f o r CQH 1 0 0 : C = 78.65, H = 8.25 ' found : C = 77.69, H = 8.07. Although the analysis is unsatisfactory, the N.M.R. spectrum showed the correct integration, and the analysis for the satur-ated alcohol (XIV) derived d i r e c t l y from t h i s compound was acceptable. Other samples of (X), (XI) and (XII) were obtained by d i r e c t separation of the o r i g i n a l reaction mixture by V.P . C . on T . C . E . P . at 130\u00C2\u00B0. The alcohols were also obtained by reduc-t i o n of the corresponding acetates (VII), (VIII) and (IX) p u r i -f i e d by V.P . C . on T . C . E . P . at 135\u00C2\u00B0. The r a t i o of alcohols (X) - 20 -a n d ( X I ) w a s e s t i m a t e d t o b e 5 t o 1 b y c o m p a r i n g t h e p e a k a r e a s o n t h e V . P . C . t r a c e . b y c u t t i n g t h e m o u t a n d w e i g h i n g t h e m . 5. P r e p a r a t i o n o f e x o - s y n - t r i c y c l o 3,2,1,0 ' o c t a n - 8 - o l ( X I I I ) : A c r u d e m i x t u r e o f e x o - s y n - t r i c y c l o [ 3 , 2 , 1 , 0 2 * o c t - 6 - e n e -8-0I ( X ) a n d t e t r a c y c l o 3 , 3 , l , 0 2 , 4 , 0 6 , 8 ] n o n a n - 9 - o l ( X I I ) , 0.166 g . , w a s d i s s o l v e d i n 10 m l . o f 95$ e t h a n o l , w i t h 0.0155 g . o f p l a t i n u m d i o x i d e a d d e d a s c a t a l y s t , a n d e x p o s e d t o h y d r o g e n g a s a t a b o u t 1.1 a t m o s p h e r e s . T h e s o l u t i o n t o o k u p 30.0 m l . o f h y d r o g e n I n a l i n e a r f a s h i o n o v e r t h i r t y - f i v e m i n u t e s a n d t o o k u p n o m o r e u p t o n i n e t y m i n u t e s . A f t e r p u m p i n g o f f t h e h y d r o g e n a n d a l l o w i n g a i r t o e n t e r t h e s y s t e m t h e c a t a l y s t w a s f i l t e r e d o f f a n d t h e e t h a n o l e v a p o r a t e d t o g i v e O.I46 g . of a c l e a r c o l o r l e s s o i l . A V . P . C . c o m p a r i s o n o n T . C . E . P . a t 130\u00C2\u00B0 w i t h t h e a n t i i s o m e r ( V ) s h o w e d c o n c l u s i v e l y t h a t t h e t w o a l c o h o l s w e r e d i f f e r e n t . T h i s w a s c o n f i r m e d b y I . R . a n d N.M.R. c o m p a r i s o n s . M . p t . 44-46\u00C2\u00B0 ( s e a l e d t u b e ) . I . R . : 3350 ( s ) , 2900 ( s ) , 1150 ( m ) , 1080 ( s ) , 1010 ( w ) , . ( 940 ( w ) , 875 ( w ) , 830 ( m ) , 770 ( m ) , 720 ( m ) , 685 ( s ) . N.M.R.: b r i d g e 6.55 ( s ) ; h y d r o x y l 6.79 ( s ) ; b r i d g e h e a d 7.9 ( s ) ; e n d o / e x o 8.75 ( m ) ; c y c l o p r o p y l 9.2 (m) ( t h r e e p r o t o n s ) , 10.1 (m) ( o n e p r o t o n ) . A n a l y s i s : c a l c u l a t e d f o r CeH^O: C = 77.38, H = 9.74, 0 = 12.88 f o u n d : C = 77.58, H = 9.70, 0 = 12.81. 6. P r e p a r a t i o n of e n d o - s y n - t r i c y c l o 3,2,l,0 2 , 4Joctan-8-ol ( X I V ) : C r u d e e n d o - s y n - t r i c y c l o 3,2,1,0 2,4 o c t - 6 - e n e - S - o l ( X I ) , 0.106 g . , w a s d i s s o l v e d i n 10 m l . o f 95$ e t h a n o l w i t h 0.0147 g - 21 -of platinum di o x i d e added as c a t a l y s t . Exposure t o hydrogen gas at 1.1 atmospheres r e s u l t e d i n a l i n e a r uptake of 12.0 ml. of gas i n f i f t e e n minutes w i t h no f u r t h e r uptake f o r the next t h i r t y minutes. A f t e r removal of hydrogen, f i l t r a t i o n of c a t a l y s t and evaporation of s o l v e n t , 0.0816 g. of a c l e a r c o l o r l e s s o i l remained. A comparison of t h i s o i l by V.P.C. on the T.C.E.P. column at 120\u00C2\u00B0 showed that the main peak was ne i t h e r of the exo Isomers (V) or ( X I I I ) . This was confirmed by I.R. and N.M.R. comparisons. M.pt. 125-127\u00C2\u00B0 (sealed tube). I.R.: 3300 ( s ) , 2900 ( s ) , 1130 ( s ) , 1060 ( s ) , 990 (w), 930 (w), 800 (w), 780 (m), 750 (w), 720 ( s ) . N.M.R.: bridge 6.0 ( s ) ; hydroxyl 6.32 (m); bridgehead 8.05 ( s ) ; endo/exo 8.6 (m); c y c l o p r o p y l 8.9 (m). A n a l y s i s : c a l c u l a t e d f o r C QH 1 20: C = 77.38, H = 9.74 found : C = 77.05, H = 9.64. 7. Pr e p a r a t i o n of e x o - a n t i - 8 - m e t h o x y - t r i c y c l o [ 3 , 2 , 1 , 0 2 > 4 ] . octane ( V I ) : ( D r i e d a l c o h o l (V), 1.0 g. (0.0081 moles), i n 10 ml. of anhydrous glyme (1,2-dimethoxyethane) was slo w l y added to a s t i r r e d suspension of 0.4 g. (0.0167 moles) of sodium hydroxide i n 50 ml. of anhydrous glyme and r e f l u x e d f o r one hour i n a 100 ml. three-necked f l a s k f i t t e d w i t h a condenser and an a d d i t i o n f u n n e l . A f t e r c o o l i n g the r e a c t i o n mixture to room temperature, 3.0 g. (0.0211 moles) of methyl io d i d e i n 10 ml. of anhydrous glyme was added f o l l o w e d by s t i r r i n g at room temperature f o r one hour. Water and d i e t h y l ether - 22 -were added to the mixture and the ether l a y e r and washings separated, d r i e d w i t h saturated aqueous sodium c h l o r i d e s o l u -t i o n and anhydrous magnesium s u l f a t e and evaporated to give 0. 92 g. (82.5%) of a y e l l o w i s h o i l which was shown to be ether ( V I ) . V.P.C. on T.C.E.P. at 80\u00C2\u00B0 showed that t h i s ether was I d e n t i c a l to the one i s o l a t e d from the r e a c t i o n of antl-7-norbornenol (IV) w i t h diazomethane. I.R. and N.M.R. spectra confirmed t h i s assignment. B.pt. 184\u00C2\u00B0/ 750 mm. 1. R.: 2950 ( s ) , 1120 ( s ) , 1070 (m), 1040 (w), 1005 (w), 995 (w), 955 (w), 900 (w), 880 (w), 810 (m), 745 (m), 710 (w), N.M.R.: methyl 6.93 (1); bridge 7.00 (m); bridgehead 7.86 ( s ) ; endo/exo 8.4 (m), 8.8 (m); c y c l o p r o p y l 9.3 (m) (three p r o t o n s ) , 10.1 (m) (one p r o t o n ) . A n a l y s i s : c a l c u l a t e d f o r C 8H 1 10CH 5: C = 78.21, H = 10.21, OCH3 = 22.41 found : C = 78.11, H = 10.16, 1 0CH 3 = 22.67 : C = 78.27, H = 10.07 8. P r e p a r a t i o n of e x o - a n t i - t r i c y c l o J5,2,l,0 2' 4~] octan-8-b r o s y l a t e (XV) (17): A l c o h o l (V), 1.0 g. (0.0081 moles), was d i s s o l v e d i n 5 ml. of anhydrous p y r i d i n e and slowly added to a s o l u t i o n of 2.2 g. (0.0081 moles) of p-bromobenzenesulfonyl c h l o r i d e - 23 -(brosyl chloride) i n 5 ml. of anhydrous pyridine at room temperature. A s l i g h t warming of the clear orange solution resulted. After standing at room temperature f o r t h i r t y minutes, c r y s t a l s of pyridine hydrochloride began to separate from the solution. After standing overnight, the r e a c t i o n mixture was heated b r i e f l y to 100\u00C2\u00B0, cooled to 0\u00C2\u00B0 and the pyridine hydrochloride c r y s t a l s dissolved by a d d i t i o n of water. The red o i l which separated upon adding water was scratched u n t i l c r y s t a l l i s a t i o n occurred. The c r y s t a l s , 1.91 g. (69$)\u00C2\u00BBwere f i l t e r e d o f f , washed with water, dried by drawing a i r through them and r e c r y s t a l l i s e d from petroleum ether (b.pt. 65-110\u00C2\u00B0). Comparison of I.R. spectra and mixed melting point with an authentic sample of the ester (17a) showed conclusively that the product was indeed (XV). M.pt. 84-85\u00C2\u00B0. I.R.: 2900 (w), 1570 (m), 1450 (w), 1350 (s), 1260 (w), 1170 (s), 1095 (m), 1065 (s), 985 (s), 905 (rn), 880 (m), 865 (m). N.M.R.: aromatic 2,33 (s); bridge 5.86 (s); bridgehead 7.74 (s); endo/exo 8.5 (m), 9.2 (m); cyclopropyl 9.3 (m). * The brosyl chloride was p u r i f i e d by d i s s o l v i n g the crude compound i n d i e t h y l ether, washing with 10$ aqueous sodium car-bonate solution to remove the a c i d , drying the ether sol u t i o n with saturated aqueous sodium chloride solution and anhydrous magnesium s u l f a t e , and evaporating the ether. The white r e s i -due was r e c r y s t a l l i s e d from petroleum ether (b.pt. 30-60\u00C2\u00B0); m.pt. 74-75\u00C2\u00B0, reported (35), 75\u00C2\u00B0. - 24 -C. PRODUCT STUDIES I. Acetolyses of exo-anti-tricyclo jj),2,l,02'4 octan-8-brosylate (XII) at 200\u00C2\u00B0 (17): a) six hours (2.4 half l i f e s (17a)) i) Brosylate (XV), 0.75 g. (0.0022 moles), was dissolved in 15 ml. of 0.11 N sodium acetate in glacial acetic acid, sealed In a thick-walled glass tube and placed In a steel bomb pre-o heated to 200 in a silicone o i l bath. After six hours the bomb was removed, cooled and the tube opened. A large amount of black solid material had separated from the solution. Excess water was added to the tube, the contents transferred to a separatory funnel and extracted with diethyl ether. The black solid dissolved in the ether resulting in a dark yellow solution. This solution was washed with water, 10$ aqueous sodium carbonate solution and f i n a l l y with saturated aqueous sodium chloride solution. The deep yellow solution was decolorised by three treatments with activated charcoal, f i l t e r e d , dried over anhydrous magnesium sulfate and evap-orated. The resulting pale yellow o i l , 0.27 g. (75$ based on total conversion to acetate) was separated on T.C.E.P. at 130\u00C2\u00B0 into two main fractions, (B) and (C), and one smaller one, (A), of shorter retention time. Ratio of peak areas, (A) to (B) to (C) was 3 to 44 to 53* The retention times were: (A), eleven minutes; (B), fourteen minutes, and (C), sixteen minutes. The I.R. spectra of the two larger peaks were con-sistent with those expected for olefin acetates but neither was the t r i c y c l i c acetate (XVI) (17a). - 25 -I.R.: (B): 3020 (w), 2950 (m), 1730 (s), 1620 (w), 1440 (m), 1380 (m), 1240 (s), 1190 (w), 1120 (w), 1080 (w), 1040 (m), 1020 (m), 975 (w), 960 (w), 910 (w), 850 (w), 710 (m). (C): 3000 (m), 2900 (m), 1730 (s), 1440 (w), 1370 (m), 1220 (s), 1180 (w), 1060 (m), 1020 (m), 960 (w), 935 (w), 900 (w), 810 (w), 730 (m), 715 (w). (XVI) (17a): 3000 (w), 2920.(m), 1730 (s), 1360 (m), 1240 (s), 1140 (w), 1080 (m), 1040 (m), 1000 (w), 960 (w), 910 (w), 810 (w), 745 (w). l i ) Brosylate (XV), 0.5 g. (0.0015 moles), was dissolved in 12 ml. of 0.11 N sodium acetate in glac i a l acetic acid, sealed in a thick-walled glass tube and placed i n a steel bomb pre-heated to 200\u00C2\u00B0 i n a silicone o i l bath. After six hours the bomb was removed from the bath, cooled, the tube opened and the contents poured into water. Black solid material had again separated from the solution. The aqueous mixture and washings were extracted with diethyl ether affording a dark yellow solution into which the black particles had dissolved, After separation of the aqueous phase, the ether solution and washings were washed with water, 10$ aqueous sodium carbonate solution and saturated aqueous sodium chloride solution. The yellow color was removed by three treatments with activated charcoal and the solution dried over anhydrous magnesium sulfate. The solution was reduced in volume to about 15 ml. and added slowly at room temperature to a magnetically stirred suspension of 0.1 g. (0.0026 moles) of finely divided lithium aluminum hydride in 25 ml. of anhydrous diethyl ether contained - 26 -i n a 100 ml. three-necked f l a s k f i t t e d w i t h a condenser and an a d d i t i o n f u n n e l . A f t e r s t i r r i n g the mixture at room temperature f o r a f u r t h e r hour, excess water and i c e were added t o hydrolyse any remaining l i t h i u m aluminum hydride. The r e s u l t i n g aqueous suspension of white aluminum s a l t s was separated from the c l e a r ether l a y e r and washed s e v e r a l times w i t h d i e t h y l e t h e r , the ether s o l u t i o n and washings being combined. The ether s o l u t i o n was washed w i t h water and s a t u r a t e d aqueous sodium c h l o r i d e s o l u t i o n and d r i e d over anhydrous magnesium s u l f a t e . Removal of the solvent gave 0.108 g. (60%) of a y e l l o w i s h o i l . This o i l was shown t o be a mixture of three a l c o h o l s by V.P.C. on the T.C.E.P. column at 140\u00C2\u00B0. The I.R. spectra of these compounds showed that the f i r s t two, (D) and ( E ) , were s i m i l a r o l e f i n i c a l c o h o l s , the t h i r d a u t h e n t i c e x o - a n t i -(D), f o u r t e e n minutes; (E), seventeen minutes, and (V), twenty-three minutes, and the peak r a t i o s , (D) t o (E) t o (V):14 t o 60 to 26.. I.R.: (D): 3350 ( s ) , 3050 (m), 2900 ( s ) , 1650 (w), 1450 (m), 1410 (m), 1310 (m), 1240 (m), 1180 (m), 1090 ( s ) , 1000 (w), 905 (w), 870 (w), 845 (w), 810 (ra), 775 (w), 730 ( s ) , 710 (w), 670 ( s ) . (E): 3300 ( s ) , 3070 (m), 2900 ( s ) , 1630 (w), 1440 (m), 1340 (m), 1260 (w), 1180 (w), 1140 (w), 1080 (m), 1060 (m), 1000 (m), 970 (m), 940 (m), 880 (w), 710 (m). b) t h i r t y hours (12 h a l f l i v e s (17a)): B r o s y l a t e (XV), 0.75 g. (0.0022 moles), was d i s s o l v e d (V). The r e t e n t i o n times were: - 27 -i n 15 ml. of 0.11 N sodium acetate i n g l a c i a l acetic acid, sealed i n a thick-walled glass tube and placed i n a s t e e l bomb which had been preheated to 200\u00C2\u00B0 i n a s i l i c o n e o i l bath. A f t e r t h i r t y hours the bomb was removed from the bath, cooled, and the glass tube opened. A very large amount of s o l i d black and brown material was i n the tube. The tube was washed with water and d i e t h y l ether, the ether layer d i s s o l v i n g the black residue. The ether layer was separated and washed with water, 10% aqueous sodium carbonate sol u t i o n and satura-ted aqueous sodium chloride sol u t i o n . The very dark color of the clear ether s o l u t i o n was removed by repeated treatment with activated charcoal. The soluti o n was dried over anhy-drous magnesium sulfate and the ether removed to give 0.08 g. (22%) of a s l i g h t l y yellowish o i l . V.P.C. of t h i s o i l on T.C.E.P. at 140\u00C2\u00B0 showed that three components, (A), (B) and (C), were present i n the r a t i o s : (A) to (B) to (C) equals 15 to 49 to 36. The two larger peaks were shown by I.R. comparison to be i d e n t i c a l to the two'collected from the six hour s o l v o l y s i s , (B) and (C). The smaller peak may be the trace (A) present i n the shorter run. Retention times: (A), twelve minutes; (B), fourteen minutes; and (C), seventeen minutes. [3,2,1,0 2' 4 octan-8-brosylate 2. Reduction of e x o - a n t i - t r i c y c l o (XV). Brosylate (XV), 0.09 g. (0.00026 moles), was dissolved i n 10 ml. of anhydrous d i e t h y l ether and slowly added to a mag-- 28 -n e t i c a l l y s t i r r e d suspension of 0.1 g. (0.0026 moles) of f i n e l y d i v i d e d l i t h i u m aluminum hydride i n 15 ml. of anhydrous d i e t h y l ether contained i n a 100 ml. three-necked f l a s k f i t t e d w i t h a condenser and an a d d i t i o n f u n n e l . A f t e r a d d i t i o n was completed, the mixture was s t i r r e d at room temperature f o r one hour. Water and i c e were then added, w i t h s t i r r i n g , t o hydrolyse the excess l i t h i u m aluminum hydride. The white aluminum s a l t s suspended i n the aqueous l a y e r were separated and the ether l a y e r and washings washed w i t h water and saturated aqueous sodium c h l o r i d e s o l u t i o n . A f t e r d r y i n g over anhy-drous magnesium s u l f a t e , the ether was removed by r o t a r y evaporation to give 0 . 0 4 g. (91.6$) of a y e l l o w i s h o i l . V.P.C. on the a c i d washed Carbowax column at 155\u00C2\u00B0 showed one peak. This compound was shown by V.P.C. comparison and by I.R. spectroscopy, t o be e x o - a n t i - t r i c y c l o | j S , 2 , l t Q 2 > 4 octan-8-ol (V). 3. A c e t o l y s i s of e x o - a n t i - t r i c y c l o (V) at 2 5\u00C2\u00B0: 3 , 2 , l , 0 2 , 4 ] o c t a n - 8 - o l A l c o h o l (V), 0.3 g. (0.0024 moles), was d i s s o l v e d at room temperature i n 25 ml. of g l a c i a l a c e t i c a c i d and 3 ml. (0.0319 moles) of a c e t i c anhydride w i t h 0.66 g. o f 70$ aqueous p e r c h l o r i c a c i d added t o the s t i r r e d s o l u t i o n . A f t e r f i f t e e n hours of s t i r r i n g at 2 5 \u00C2\u00B0 water was added t o the s l i g h t l y y e l l o w i s h s o l u t i o n . The aqueous s o l u t i o n was e x t r a c t e d w i t h d i e t h y l e t h e r , the ether l a y e r and washings washed w i t h 10$ aqueous sodium carbonate s o l u t i o n , water, - 29 -and saturated aqueous sodium chloride solution. After drying the ether solution over anhydrous magnesium sulfate the sol-vent was removed by rotary evaporation to give 0.5 g. (125$) of a slightly yellowish o i l . V.P.C. on the T.C.E.P. column at 140\u00C2\u00B0 showed only two peaks, ( F j and (G), widely separated in retention time ( ( F ) , nine minutes, and (G), one hundred and eleven minutes). The I.R. spectra showed that both products were acetates. The ^ .M.R. spectra showed that ( F ) (25$ of the mixture) was an acetate with an endocyclic olefin group as evidenced by the multiplicity and chemical shift of the olefinic protons (36). The integration indicated that two olefinic protons were present. (G), (75%) was a diacetate as shown by the N.M.R. spectrum. I.R.: ( F ) : 3000 (m), 2950 (m), 1740 (s), 1640 (w), 1440 (m), 1380 (m), 1360 (m), 1240 (s), 1180 (m), 1040 ( r o ) , 1020 (m), 970 (w), 910 (w), 890 (w), 825 (w), 735 (m), 695 (w), 675 (w). (G): 2950 (s), 1730 (s), 1440 (m), 1360 (s), 1300 (m), ! 1220 (s), 1180 (m), 1160 (m), 1100 (w), 1080 (m), 1050 (m), 1020 (s), 960 (m), 900 (m), 840 (w), 825 (w), 770 (w), 670 (w). N.M.R.: ( F ) : olefinic 4.29 (m) (one proton), 4.66 (m) (one proton); bridge 5.14 (s); acetate 8.08 (1); others 7.67 (m), 8.19 (m) (eight protons). (G): adjacent to acetate groups 5.05 (s) (one proton), 5.22 (m) (one proton); acetates 8.05 ( D , 8.12 (1); others 7.8 (m) (two protons); 8 .5 (m) (eight protons). - 30 -The acetate mixture, 0.18 g., in 10 ml. of anhydrous diethyl ether was added to a magnetically stirred suspension of 0.1 g. (0.0026 moles) of finely divided lithium aluminum hydride in 25 ml. of anhydrous diethyl ether at room tempera-ture contained in a 100 ml. three-necked flask f i t t e d with a condenser and an addition funnel. Following total addition the mixture was stirred for a further two hours. An excess of water and ice was then slowly added to hydrolyse any remaining lithium aluminum hydride and to disperse the pre-cipitated aluminum salts. The aqueous layer was separated and washed with diethyl ether. The ether layer and washings were washed with water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evapora-ted to give 0.05 g. of a slightly yellowish o i l . This o i l was purified on T.C.E.P. at 140\u00C2\u00B0 to give a pure solid alcohol (H), m.pt. 108-109\u00C2\u00B0 (sealed tube). I.R.: 3250 (s), 1640 (w), 1180 (m), 1070 (s), 1060 (s), 1010 (s), 965 (m), 955 (m), 895 (m), 870 (ra), 825 (m), 735 (a), 1 700 (w), 680 (m). N.M.R.: olefinic 4.35 (m) .(one proton), 4.70 (m) (one proton); bridge 6.05 (s); hydroxyl 6.81 (s); aliphatic 7.95 (m); endo/exo 8.3 (m) (two protons), 8.8 (m) (two protons). Reported (37) for anti-bicyclo 3,2,lJoct-2-ene-8-ol: m.pt. 110-111\u00C2\u00B0. I.R.: 3628, 3489, 1179, 1072, 1059, 1013, 962. N.M.R.: 4.44 (m); 5.87 (s); 6.76 (m); 7.84 (m). The reported spectra for the syn isomer are incompatible with the observed spectra. I I I . SUMMARY OP EXPERIMENTAL RESULTS A. SYNTHETIC The synthesis of anti - 7-norbornenol (V) was c a r r i e d out according to the procedure of Story ( 3 2 ) . Norbornadiene ( I ) , obtained commercially, was reacted with commercial t-butyl perbenzoate i n benzene to give the ether 7-^-butoxynorborna-diene ( I I ) . Acid cleavage of the ether with g l a c i a l acetic acid, acetic anhydride and 7 0 $ perchloric acid gave the ester 7-norbornadienyl acetate ( I I I ) . Lithium aluminum hydride reduction of (III) gave anti - 7-norbornenol (IV) e x c l u s i v e l y . Reacting (IV) with diazomethane i n the presence of [ 3 , 2 , 1 , \" 2 ' 4 octan - 8-ol cuprous chloride gave e x o - a n t l - t r i c y c l o | 3 , 2 , 1 , 0 (V) and exo-anti - 8-methoxy-tricyclo [ 3 , 2 , 1 , 0 * \" * ^ octane (VI). No trace of the desired endo isomer of (V) could be found In this reaction. When 7-norbornadienyl acetate (III) was reacted with diazomethane and cuprous chloride a 5 to 1 mixture, of the two monoadducts exo-syn-tricyclo o c t - 6 - e n e - 8 -acetate (VII) and endo-syn-tricyclo [ 3 , 2 , 1 , 0 2 \u00C2\u00BB ^ ] o c t - 6 - e n e - 8 -acetate (VIII) were formed, along with a diadduct tetracyclo j ^ 3 , 3 , l , 0 2 , 4 , 0 D \" \u00C2\u00BB 8 nonan -9-acetate (IX) of unknown stereochem-i s t r y . Reduction of the acetate mixture with lithiu m aluminum hydride gave the o l e f i n i c alcohols exo-syn-tricyclo J 3 , 2 , l , 0 2 , ^ j o c t - 6 - e n e - 8 - o l (X) and endo-syn-tricyclo | 3 , 2,l,Q 2 , 4 j oct - 6-ene-- 3 3 -3 , 3 , 1 , 0 2 ' V ' 8 ] 8-ol (XI) and the saturated alcohol t e t r a c y c l o nonan-9-ol (XII) of unknown stereochemistry. The stereochem-i s t r y of the o l e f i n i c products was established by chemical and nuclear magnetic resonance spectroscopy evidence. Reduc-t i o n of (X) with hydrogen gas and platinum resulted i n formation of exo-syn-tricyclo J 3 , 2 , l , 0 2 ' 4 octan-8-ol (XIII). Similar treatment of (XI) gave the endo isomer endo-syn-tricyclo 3,2,1,0 2' 4 octan-8-ol (XIV). Both of the saturated alcohols (XIII) and (XIV) were shown to be d i f f e r e n t from the known octan-8-ol (V). A l l the 3,2,1,0 2' 4 (17b) e x o - a n t i - t r i c y c l o [ 3 , 2 , 1 , 0 2 , 4 a l c o h o l i c and ester compounds prepared were separated and p u r i f i e d by gas chromatography. e ^ - a j r v ^ i - T r i c y c l o octan-8-brosylate (XV) was prepared by reacting alcohol (V) with \u00C2\u00A3-bromobenzene sul f o n y l chloride i n anhydrous pyridine, and p u r i f y i n g by r e c r y s t a l l i s i n g from petroleum ether (b.pt. 65-110\u00C2\u00B0). B. SOLVOLYSIS STUDIES The a c e t o l y s i s of brosylate (XV) was studied i n an attempt 1 to determine the rate c o n t r o l l i n g step of the reaction. At 200\u00C2\u00B0 i n a solution of 0.11 N sodium acetate i n g l a c i a l acetic acid a l l the products were rearranged acetates. At 2 5 \u00C2\u00B0 i n an acetic a c i d , acetic anhydride, perchloric a c i d mixture alco-hol (V) gave two products, one the known acetate (37) a n t i -b i c y c l o 3,2,ljoct-2-ene-8-acetate (XVII) and the other pro-ducts of addition to (XVII). Acetate (XVII) was reduced to the alcohol ( 3 7 ) a n t l - b i c y c l o J3,2,lj oct-6-ene-8-ol (XVIII) 0$ -by l i t h i u m aluminum hydride. Acetate (XVII) was not found i n the s o l v o l y s i s reactions at high temperature. These r e s u l t s indicate that the rate c o n t r o l l i n g step i s formation of a carbonium ion at Cs, rather than i n i t i a l opening of the cyclo-propyl r i n g . Formation of the carbonium ion may be followed by rearrangement thereby destroying the cyclopropyl r i n g . - 35 -IV. DISCUSSION A. SYNTHESIS ) The work of Story (32) i n preparing 7-substituted nor-bornadienes and norbornenes provides an easy method for such syntheses i n contrast to the previous method\u00E2\u0080\u0094that of D i e l s -Alder condensation of cyclopentadienes with various dieno-p h i l e s . The synthesis of 7-norbornadienyl acetate and a n t i -7-norbornenol was quite straightforward and suffered only through the low y i e l d of the f i r s t step of preparing 7-t-butoxynorbornadiene. Since norbornadiene and t - b u t y l perbenzoate are r e a d i l y available commercially, t h i s i s not too great a disadvantage. Among the three general synthetic routes to cyclopropyl substituted norbornenes and norbornadienes, only the von E. Doering and Roth procedure (27) was found to be us e f u l . The Diels-Alder reaction which one would expect to give predom-inantly the desired endo isomer (19) i s not useful,because the oxygen substituted cyclopentadiene required i s not stable, and because cyclopropene i s d i f f i c u l t to prepare. The oxygen substituent cannot be added a f t e r formation of the cyclopropyl group because the a c i d i c conditions used i n Story's procedure (32) are severe enough to destroy the three membered r i n g . The Simmons-Smith procedure (26) i s not applicable to some norbornenes and norbornadienes (17b). It w i l l not add r e a d i l y to antl - 7-norbornenol although small y i e l d s of an adduct of unknown stereochemistry have been reported by Cope - 36 -(38). The Simmons-Smith reagent i s a deactivated form of carbene,the reactive species being iodomethyl zinc Iodide (26) formed by reaction of methylene iodide with zinc copper couple. Although carbene i t s e l f reacts indiscriminately by in s e r t i o n and addition reactions i t s deactivated forms react by addition s t e r e o s e l e c t i v e l y . The Simmons-Smith reagent w i l l not react with aromatic systems but adds to norbornene i n a highly stereospecific manner (18, 26d, 27) i n d i c a t i n g some coordination between the o l e f i n and the reagent (39). Although the reagent i s r e a d i l y decomposed by water and saturated alcohols (26c), i t w i l l react with cyclohexene-3-ol (39) i n d i c a t i n g that some competition between methylene transfer and destruction of the reagent may be operative. Simmons and Smith report that a complex between the reagent and oxygen atoms may form (figure 7) (26c). b a c figure 7 The complex (figure 7a) can decompose either by the methylene transfer reaction to 7b or by decomposition to 7 c . It i s clear - 37 -that methylene transfer can occur only i f the stereochemistry of the complex 7a i s correct, but i n the case of anti-7-norbor-nenol, the methylene group i n the complex i s too remote from the double bond to undergo methylene transfer intramolecularly, although intermolecular transfer i s possible. Thus one should expect low yi e l d s of adducts by reacting anti-7-norbornenol with t h i s reagent. This has been confirmed by Cope (38). On the other hand, the cuprous chlpride catalysed reaction of diazomethane with anti-7-norbornenol occurs quite r e a d i l y . Like the Simmons-Smith reagent a deactivated form of carbene i s involved but i n th i s case the carbene i s reactive enough to add to aromatic systems (28). A mechanism has been proposed (28) i n which the nucleo-p h i l i c carbon from one of the resonance forms of diazomethane f i l l s the vacant o r b i t a l of Cu 1 (figure 8): \u00C2\u00A9 \u00C2\u00A9 \u00C2\u00A9 \u00C2\u00A9 \u00C2\u00A9 \u00C2\u00A9 CH2=N=N \u00C2\u00AB \u00E2\u0080\u0094 > N=N-CH2 \u00C2\u00BB Cl-Cu-CH2-N^N figure 8 Simultaneous or successive s p l i t t i n g off of the nitrogen occurs to leave a carbene-copper complex which attacks the double bond (figure 9). ;H 2 +CuCI figure 9 - 38 -Support for t h i s type of mechanism comes from the f a c t that the reaction mixture becomes dark with a metallic coating on the sides of the f l a s k i n d i c a t i n g reduction of the copper by acceptance of electrons. The predominance of exo product i n reaction with norbornenes i s expected on grounds of preferred exo attack on the norbornene skeleton (40). Indeed i n the rea c t i o n of norbornene i t s e l f with iodomethyl zinc iodide, Simmons and Smith report (26d) no formation of the endo isomer at a l l . Norbornadiene however, reacts to give a 5.7 to 1 mixture of exo to endo adducts (26d). Since addition to 7-norbornadienyl acetate (III) occurs only at the syn double bond (see STRUCTURAL PROOF below) i t seems that the acetate group plays some r o l e i n d i r e c t i n g the attack of th i s reagent as do alcohol groups with the Simmons-Smith reagent (26c). B. STRUCTURAL PROOF: The proof of structure of the compounds prepared for t h i s work was done through chemical evidence and N.M.R. spectral evidence. The syn double bond of 7-norbornadienyl acetate i s r e a d i l y reduced with the ester group by lithium aluminum hydride (32) (figure 10a). It has also been shown that syn-7-norbornenol w i l l reduce with lithium aluminum hydride to 7-norbornanol (figure 10b) whereas the a n t i isomer i s inert (figure 10c) (41). - 39 -figure 10 It was f e l t that methylene addition products should undergo similar reduction of syn o l e f i n i c groups while a n t i double bonds would be expected to remain unreduced (figure 11). figure 11 - 40 -No difference i n reduction properties were expected between the exo and endo isomers of methylene addition products. The two o l e f i n i c acetates (VII) and (VIII) when reduced with l i t h i u m aluminum hydride gave the corresponding o l e f i n i c alcohols (X) and (XI) in d i c a t i n g thet the acetate function was a n t i to the double bond i n both cases (figure 1 2 ) : figure 12 Further chemical evidence for t h i s assignment resulted from the c a t a l y t i c reduction of both (X) and (XI), neither of which gave the alcohol (V) of known stereochemistry (17b) (figure 13). - 41 -V figure 13 The N.M.R. spectra further supported this assignment. In a recent paper, Snyder and Franzus (42) report that long range coupling occurs between the o l e f i n i c protons and the bridge proton i n norbornenes and norbornadienes substituted at C\u00E2\u0080\u009E (figure 14) figure 14 They' point out that the coupling i s much greater i n the cases i n which the bridge proton i s a n t i to the double bond (figure 14a) than i n the corresponding syn cases (figure 14b). Thus for 14a one expects the long range s p l i t t i n g R^-Hy to give a multiplet for R2. In 14b the s p l i t t i n g H2-H7 Is quite small r e s u l t i n g i n a t r i p l e t for R^. For 7-.t-butoxynorbornadiene (II) and 7-norbornadienyl acetate (III) two o l e f i n i c peaks were observed. One approximated a t r i p l e t , with the inner l i n e sometimes s l i g h t l y s p l i t , whereas the other, at s l i g h t l y - 42 -higher f i e l d , approximated a pair of t r i p l e t s (42) and was considerably broader. The product acetates, (VII) and (VIII/, and the corresponding alcohols, (X) and (XI), a l l had o l e f i n i c peaks that were t r i p l e t s , not complex multiplets. This e v i -dence indicated that the assignment of the double bond a n t l to the Cg substituent was correct. The stereochemistry of the cyclopropyl group can also be determined from the N.M.R. spectrum. In the case of the adducts between norbornadiene and ethyl diazoacetate (figure 15), Sauers and Sonnet (43) report that the endo isomer (figure 15b) has an up f i e l d s h i f t of 0.6 T units for the o l e f i n i c protons with respect to those of the exo isomer (figure 15a). / J ^ C O O E t figure 15 They a t t r i b u t e t h i s chemical s h i f t to induced sh i e l d i n g of the o l e f i n i c protons by the r i n g current of the cyclopropyl group i n 15b, since t h i s isomer has the best geometry for such an in t e r a c t i o n (43). Although the N.M.R. spectrum of exo- t r i c y c l o J 3 , 2 , l , 0 2 ' 4 oct-6-ene (figure 16a) has not been reported, the endo isomer (figure 16b) has the o l e f i n i c peak at 4.36T, an u p f i e l d s h i f t of 0.3 T units from that of nor-- 43 -bornene (figure 16c) (18). a b c .figure 16 It i s expected that the isomer 16a w i l l resonate at about 3.65 T, a downfield s h i f t of about 0.4 T from that of norbor-nene (figure 16c). Similar r e s u l t s were obtained f o r the two acetates (VII) and (VIII) and f o r the alcohols (X) and (XI) with s h i f t s of 0.58 T units and 0.71 T units r e s p e c t i v e l y . The r a t i o s of the two monoadducts also indicates that the stereochemical assignments were i n fact correct. Simmons and Smith (26d) report that addition of the Simmons-Smith reagent to norbornadiene gave a mixture of exo and endo adducts i n the r a t i o of 5.7 to 1, and f e e l that t h i s r e s u l t Is consistent with preferred exo attack on the norbornene skeleton. In t h i s work the r a t i o of exo to endo products has been established to be 5 to 1. Since the mechanisms of the Simmons-Smith reaction and the cuprous chloride catalysed diazomethane addition are s i m i l a r , t h i s r a t i o has been taken as evidence of formation of an exo-endo p a i r of isomers. On these bases the stereochemistry of the cyclopropyl group, v i z , whether i t was endo or exo was assigned. - 44 -The N.M.R. spectrum was useful i n two other ways. The protons of the 7-oxygen substituted norbornene skeleton are a l l quite unique i n t h e i r chemical s h i f t s although the peaks are often badly s p l i t . For t h i s reason the f a m i l i a r pattern of resonance peaks was taken as evidence that the norbornene skeleton had not been broken up during any r e a c t i o n . The appearance of peaks at above 8.8 T was taken as evidence of cyclopropyl groups being present in the molecule although some peaks appeared at lower f i e l d . In such cases the in t e -gration was used to confirm the assignment. The I.R. spectra were used mainly as a physical constant of the compound i n question. The usual regions were examined for hydroxyl, acetate and o l e f i n i c groups. Bellamy (44) reports that the presence of a cyclopropyl group can be detected i n two regions of the I.R. spectrum. The s t r a i n of the r i n g s h i f t s the C-H stretching mode to higher wave number by about 150 cm\"\ Thus one expects a band at about 3050 cm\"-'- for compounds with cyclopropyl protons. The other band' of i n t e r e s t i s a weak one at about 1020 cm\"^ - due to a r i n g deformation mode (44b) but some workers (44c) f e e l that i t alone i s not s u f f i c i e n t evidence to enable assignment of a cyclopropyl r i n g e s p e c i a l l y i n oxygenated compounds. In t h i s work the spectra were obtained on a Perkin-Slmer I n f r a -cord with only moderately good re s o l u t i o n . This fact together with the occurrence of large bands on either side of the expected weak bands expected for cyclopropyl compounds did - 45 -not enable one to observe these bands i n a l l cases. Perhaps with a better spectrophotometer t h i s d i f f i c u l t y could be overcome. The stereochemistry of the diadduct acetate (IX) and the corresponding alcohol (XII) was not proved. The N.M.R. spectrum Indicates that the compounds are probably mixtures of at le a s t two isomers although the V.P.C. trace indicated no separation. From the i s o l a t i o n of the endo and exo, syn monoadducts one would expect that at least two Isomers are formed. Simmons and Smith's work on norbornene (26d) and the present work on anti-7-norbornenol indicate that only the exo product i s formed on addition to norbornenes. I f th i s case i s analogous one would expect only exo addition to the second double bond of norbornadienyl acetate giving r i s e ultimately to only two isomers of diadduct. The N.M.R. spectrum i s consistent with that expected f o r the tetracyclo [3,3,1,0 2' 4,0 6\u00C2\u00BB 8 nonane skeleton. Recently, Baylouny and Jaret (45) report spontaneous rearrangement of such a skele-r 2,8 4,61 ton'to the tetracyclo [3,3,1,0 ,0 J skeleton which i s expected to have a much s i m p l i f i e d N.M.R. spectrum. This aspect w i l l be discussed l a t e r (see SUGGESTIONS FOR FURTHER RESEARCH, page 51 below). C. SOLVOLYSIS STUDIES In 1964, Pineock and Wells (17a) studied the rates of acetol y s i s of ex o - a n t l - t r i c y c l o [3.2.1.02'4' octan-8-brosylate (XV), 7-norbornyl brosylate and anti-7-norbornenyl brosylate, - 46 -Recently LaLonde and coworkers (46) have studied the acid catalysed cleavage of cyclopropane ri n g s . The mechanism of t h i s reaction has been interpreted i n terms of the most stable carbonium ion intermediates formed by the e l e c t r o p h i l i c addition of a proton to the r i n g . I t was found however, that acetic a c i d would not open the cyclopropyl r i n g of norcarane at 46.5\u00C2\u00B0 for one week unless small amounts of a strong a c i d were added (46a). LaLonde and Batelka (46d) report I s o l a t i o n of r i n g cleaved o l e f i n s (20$) and of f i v e poorly resolved acetates (80$) formed by addition to the carbonium Ion formed i n the acid catalysed a c e t o l y s i s of e x o - t r l c y c l o jj?,2,l,0^' 4joctane (figure 17). o l e f i n s acetates figure 17 The o l e f i n mixture was not analysed. The acetates were reduced to six alcohols and analysed (figure 18). 28$ trace three isomeric methylbicyclo i? 2 , 2 , 1 heptanols 28$ figure 18 - 47 -Several product studies of the a c e t o l y s i s of brosylate (XV) were c a r r i e d out i n an attempt to show that the rate c o n t r o l l i n g step was formation of a carbonium ion at Cg. A s o l v o l y s i s of the corresponding alcohol (V) i n acetic a c i d , acetic anhydride and perchloric acid at 25\u00C2\u00B0 resulted i n com-plete cleavage of the cyclopropyl r i n g to give two products, both acetates. The smaller f r a c t i o n (25$ of the mixture), was subsequently shown by reduction to the known (37) alcohol a n t i - b i c y c l o 3,2,1 oct-2-ene-8-ol (XVIII), to be a n t i - b i c y c l o |3,2,l] oct-2-ene-8-acetate (XVII). The other product (75$) was a diacetate r e s u l t i n g from addition of acetate ion to the carbonium ion intermediate (46d) (figure 19). A C \u00C2\u00B0 ~ T V dlacetates XVII figure 19 Because no other o l e f i n acetates were found i t was assumed that the cyclopropyl r i n g opens almost exclusively i n a speci-f i c manner to give the r i n g expanded carbonium Ion. F a i l u r e - 48 -2,2,2 octane to Isolate the o l e f i n acetate with the b i c y c l o skeleton i s taken as evidence either that the equilibrium i s not very important or that the resultant carbonium ion does not eliminate a proton very r e a d i l y . The occurrence of only one compound upon reduction of the acetate mixture has been interpreted i n t h i s work as reduction of the diacetate to a d i o l which remains on the gas chromatography column. In support of t h i s claim i s the observation that the diacetate has such a long reten-t i o n time, and the further observation that the alcohols among the compounds prepared have much longer retention times than do the corresponding acetates. It i s possible that a mixture of diacetates was present because the gas chromatography columns avail a b l e are not very e f f i c i e n t for separation of acetates. None of the cyclopropyl acetate (XVI) could be i s o l a t e d from the high temperature s o l v o l y s i s . However l i t h i u m alum-inum hydride reduction of the mixture of products obtained a f t e r a c e t o l y s i s at 200\u00C2\u00B0 for six hours resulted i n a mixture containing s.ome cyclopropyl alcohol (V). This alcohol was subsequently shown to re s u l t from reduction of the s t a r t i n g brosylate (XV) which does not i t s e l f come o f f the gas chrom-atography column. This product makes up 26% of the mixture whereas that expected for 2.4 half l i v e s i s 19%. Slight differences i n concentrations from the k i n e t i c work of Wells (17a) on t h i s compound or differences i n detector s e n s i t i v i t y to d i f f e r e n t compounds may account f o r t h i s difference. - 49 -O A Although none of the expected e x o - a n t i - t r i c y c l o |_5,2,1,0 * octan - 8-acetate (XVI) was is o l a t e d from the s o l v o l y s l s reac-t i o n s , i t i s currently f e l t that the rate c o n t r o l l i n g step Is i n fact formation of a carbonium ion at Cg. This r e s u l t i s supported by four observations. F i r s t l y , LaLone (46a) gets no cyclopropyl r i n g opening unless strong acid i s present i n the s o l v o l y s i s solutions. Because no strong electrophile was present i n our solutions i t i s f e l t that cyclopropyl r i n g opening was a secondary reaction. Secondly, no dlacetates were found i n the high tempera-ture s o l v o l y s i s products. I f any diacetate i s formed i t may be present i n the large amount of charred material l e f t i n the reaction tubes. This material probably r e s u l t s i n the low y i e l d s obtained, e s p e c i a l l y i n the longer runs. I f r i n g cleavage occurred either before or after formation of a car-bonium Ion at Cg, one would expect to is o l a t e a diacetate analogous to the one i s o l a t e d from the acid catalysed r i n g opening at room temperature. For this reason i t i s f e l t that 1 the primary rate c o n t r o l l i n g process i s generation of a carbonium ion at Cg which then undergoes rearrangement cleaving the cyclopropyl group. A great number of products are possible since reactive s i t e s arise from both the brosy-late group as well as the cyclopropyl group. Figure 20 shows some of the p o s s i b i l i t i e s . - 50 -figure 20 Th i r d l y , Wells (17a) has studied the rearrangement of e x o - a n t l - t r i c y c l o J 3\u00C2\u00BB2,l,0 2 > 4 J octan-8-acetate (XVI) i n acetic acid containing 0.11 N sodium acetate at 200\u00C2\u00B0 and found the rate of rearrangement to be considerably slower (half l i f e 9 hours) than the rate of s o l v o l y s i s of the brosylate. This observation has been interpreted as i n d i c a t i n g that the p r i -mary process i s formation of the carbonium ion at Cg (17a). Las t l y , the f a c t that the products from the room tem-perature, acid catalysed cyclopropyl r i n g cleavage reaction are d i f f e r e n t from the products of high temperature acetoly-s i s indicates that a d i f f e r e n t mechanism of r i n g opening i s i n e f f e c t . Since one expects the most stable carbonium ion - 51 -intermediate to be formed i n both cases i t seems clear that the high temperature r i n g cleavage i s a secondary r e a c t i o n not the primary one since i f the same reaction were occurring, the same r i n g opened products should be formed. D. CONCLUSIONS It appears that no ready method i s available f o r synthesis [ 3 , 2 , 1 , \" 2 ' < octan-8-ol. Methylene addi-of endo-antl-tricyclo [ , 0 t i o n to anti - 7-norbornenol (V) gave only the exo adduct. Addi-t i o n to the diene 7-norbornadienyl acetate (III) res u l t e d i n monoaddition to only the syn double bond with formation of both endo and exo isomers i n the r a t i o of 1 to 5 . Diadduct formation also occurred. It might be possible to invert the configuration about C3 of the syn monoadducts but as a route to preparation of the amounts of alcohols necessary f o r k i n e t i c studies t h i s seems formidable because of the problems of sep-arating and p u r i f y i n g the p r o d u c t s \u00E2\u0080\u0094 a l l of which has been done by gas chromatography up to now. The s o l v o l y s i s studies strongly indicated that the rate c o n t r o l l i n g step i n the ace t o l y s i s of brosylate (XV) i s forma-t i o n of a carbonium ion at C Q. This ion then rearranges to ' destroy the cyclopropyl moiety. E. SUGGESTIONS FOR FURTHER RESEARCH Although Baylouny and Jaret (45) report that norborna-diene reacts with methyl diazoacetate to give two diadducts that spontaneously rearrange to the tetracyclo [ 3 , 3 , 1 , 0 2 , 8 , 0 4 ' \u00C2\u00B0 ] nonane skeleton from the expected t e t r a c y c l o [ 3 , 3 , 1 , 0 2 , 4 , 0 ^ ' 8 J - 52 -nonane skeleton (figure 21), no such rearrangement was observed i n the present research. CuSO, MeOOC MeOOCCHN 800 MeOO MeOOC COOMe COOMe MeOOC COOMe COOMe figure 21 In view of these r e s u l t s i t should be in t e r e s t i n g to look at possible rearrangements of the suitable compounds prepared i n t h i s work. It does not appear that thermal isomerisation w i l l be a f r u i t f u l attempt because the diadducts prepared have a l l been p u r i f i e d by V.P.C. with i n j e c t o r and detector temperatures above 200\u00C2\u00B0. Norbornadiene (47) and 7-norbornadienyl acetate (48) have been shown to undergo photochemical rearrangement heptane and the corresponding to tetracyclo [2,2,1,0 2' 6,0 5 , 5 acetate (figure 22). - 53 -figure 22 Because cyclopropyl groups have mobile electrons s i m i l a r to those of double bonds (2,3), i t i s expected that cyclopropyl groups w i l l photochemically rearrange i n an analogous manner to the reaction of 7-norbornadienyl acetate (figure 22) and to the reaction pf Baylouny and Jaret (figure 21). The possible rearrangements are given i n figure 23. figure 23 - 54 -The N.M.R. spectra of these compounds should be quite d i s t i n c t and greatly s i m p l i f i e d from those of the s t a r t i n g acetates. Any i n t e r a c t i o n between the r i n g currents of the two cyclopropyl.rings should be exemplified by a down-field s h i f t of the methylene protons i n an analogous manner to the s h i f t s f o r para-cyc1ophanes (49). This work w i l l be under-taken sho r t l y . i - 55 -V. REFERENCES 1. C.A. Coulson and W.E. Moffit: Phil. Mag., 40, 1, (1949). 2. E.N. Trachtenberg and G. Odain: J. Am. Chem. Soc, 80, 4018, (1958). 3. R. Fuchs and J. Bloomfield: J. Org. Chem., 28, 910, (1963). 4a. J.D. Roberts and C. Green: J. Am. Chem. Soc, 68, 214, (1946). b. H.E. Smith and R.H. Eastman: J. Am. Chem. Soc, 79, 5500, (1957). 5. L.I. Smith and E.R. Rogier: J. Am. Chem. Soc, 73, 3840, (195D. 6. I.M. Klotz: J. Am. Chem. Soc, 66, 88, (1944). 7. R.J. Mohrbacher and N.H. Cromwell: J. Am. Chem. Soc, 79, 401, (1957). 8a. D.J. Patel, M.E.H. Howden and J.D. Roberts: J. Am. Chem. Soc, 85, 3218, (1963). b. K.B. Wiberg and B.J. Nist: J. Am. Chem. Soc, 85, 2788, (1963). 9, F,N, Baumgartner and R.C, Fuson: J. Am. Chem. Soc, 70, 3255, (1952). ~~ 10a. H. Hart and M. Sandri: J. Am. Chem. Soc, 81, 320, (1959). b. R.A. Sneen and A.L. Baron: J. Am. Chem. Soc, 83, 614, (1961). ~\" c. R. Breslow, J. Lockhart and A. Small: J. Am. Chem. Soc, 84, 2793, (1962). 11. H. Hart and P. Law: J. Am. Chem. Soc, 84, 2462, (1962). 12. S. Wlnstein and M. Dimmonetta: J. Am. Chem. Soc, 7 6 , 18, (1954). 13. S. Winstein and M. Shatavsky: Chem. and Ind. 56 (1956). 14. S. Winstein, M. Shatavsky, C.J. Norton and R.B. Woodward: J. Am. Chem. Soc, 77, 4183, (1955). 15. J.D, Roberts, F.O. Johnson and R.A. Carboni: J. Am. Chem. Soc, ]6, 5692, (1954). - 56 -16a. H.C. Brown: \"Transition State\" Special Publication No. 16, The Chemical Society, London (1962), 140-158, 174-178. b. H.C. Brown and H.M. B e l l : J. Am. Chem. S o c , 85, 2324, (1963). ~~ 17a. J.I. Wells: M. Sc. Thesis, University of B r i t i s h Columbia, 1964. ' b. R.E. Pincock and J.I. Wells: J. Org. Chem., 29, 965, (1964). c. R.E. Pincock and J.I. Wells: unpublished r e s u l t s . 18. K. B. Wiberg: J. Am. Chem. S o c , 82, 6375, (I960). 19. R. B. Woodward and T.J. Katz: Tetrahedron, 5, 70, (1959). 20a. B.S. Khambata and A. Wassermann: Nature, Lond. 138, 368, (1936). b. G.B. Kistiakowsky and W.H. Mears: J. Am. Chem. Soc, 58, 1060 (1936). c R.B. M o f f i t t : Organic Syntheses, 32, 41, (1952). Wiley, New York. 21a. D. Craig: J. Am. Chem. S o c , 73, 3889, (1951). b. J.A. Berson and R.D. Reynolds: J. Am. Chem. S o c , 77, 4434, ( 1 9 5 5 ) . ~ ~ c. J.A. Berson, R.D. Reynolds and W.M. Jones: J. Am. Chem. Soc, 78, 6049, (1956). d. J.E. Baldwin and J.D. Roberts: J. Am. Chem. S o c , 85, 115, (1963). i . 22a. W. von E. Doering and A. K. Hoffmann: J. Am. Chem. S o c , 76,'6162, (1954). b. P. S. S k e l l and A. Y. Garner: J. Am. Chem. S o c , 78, 3409, (1956). \u00E2\u0080\u0094 23. W.E. Parharaand P.C. Loew: J. Org. Chem., 23, 1705, ( 1 9 5 8 ) . 24. W.R. Moore, W.R. Moser and J.E. LaPrade: J.. Org. Chem., 28, 2200, (1963). 25a. G.L. Closs and L.E. Closs: J. Am. Chem. S o c , 82, 5723, (1960). . ~~ - 57 -b. G.L. Closs and G.M. Schwartz: J . Am. Chem. S o c , 82, 5729, (1960). 26a. H.E. Simmons and R.D. Smith: J . Am. Chem. S o c , 80, 5323, (1958). b. H.E. Simmons and R.D. Smith: J . Am. Chem. S o c , 81, 4256, (1959). c. H.E. Simmons and E.P. Blanchard: J . Am. Chem. S o c , 86, 1337, (1964). d. H.E. Simmons, E.P. Blanchard and R.D. Smith: J . Am. Chem. S o c , 86, 1347, (1964). 27. W. von E. Doering and W.R. Roth: Tetrahedron, 19, 715, (1963). ~ ~ 28. E. M u l l e r and H. F r i c k e : Ann., 661, 38, (1963). 29a. W. von E. Doering, R.G. Bu t t e r y , R.G. La u g h l i n and N. Chaudhuri: J . Am. Chem. Soc., 78, 3224, (1956). b. W. von E. Doering and P. LaFlamme: J . Am. Chem. S o c , 78, 5447, (1956). c. J.H. Knox and A.F. Trotman-DIckson: Chem. and Ind., 1039, (1957). d. H.M. Frey: J . Am. Chem. S o c , 80, 5005,(1958). 30. Th. J . de Boer and H.J. Backer: Organic Syntheses, C o l l . Vol. IV, 250, (1963). 31. M.E. Tate and C T . Bishop: Can. J . Chem., 40, 1043, , (1962). ~~ 32. P.R. Story: J . Org. Chem., 26, 287, (1961). 33. P. Arndt: Organic Syntheses, C o l l . V o l . I I , 461, (1959). 34. L.F. F i e s e r : Experiments i n Organic Chemistry, T h i r d E d i t i o n , 287, 288, (1957). D.C. Heath and Co., Boston, Mass. 35. Handbook of Chemistry and P h y s i c s , Forty-second E d i t i o n , 844, (1960-1961). Chemical Rubber P u b l i s h i n g Co., Cleveland, Ohio. 36. L.M. Jackman: A p p l i c a t i o n s of Nuclear Magnetic Resonance Spectroscopy i n Organic Chemistry, 61, (1959). Pergamon Press, New York, N.Y. - 58 -37. N.A. LeBel and L.A. Spurlock: Tetrahedron, 20, 215, (1964). 38. A.C. Cope, S. Moon, C.H. Park and G.L. Woo: J. Am. Chem. Soc, 84, 4865, (1962). 39. W.G. Dauben and G.H. Berezin: J. Am. Chem. Soc, 85, 468, (1963) . 40. E.L. E l i e l : Stereochemistry of Carbon Compounds, 303, (1962) . McGraw-Hill Book Co. Inc., Toronto, Ont. 41. B. Pranzus and E.I. Snyder: Division of Organic Chemistry of the American Chemical Society, Abstracts of Papers Presented at the 148th Meeting of the American Chemi-cal Society, Abstract 82. 46S, (1964). 42. E.I. Snyder and B. Franzus: J. Am. Chem. Soc, 86, 1166, (1964) . \" ~ 43. R.R. Sauers and P.E. Sonnet: Chem. and Ind., 786, (1963). 44a. L.J. Bellamy: The Infra-red Spectra of Complex Molecules, Second Edition, 29, (1958). Methuen and Co. Ltd., London, England. b. J.M. Derfer, E.E. Pickett and C.E. Boord: J. Am. Chem. Soc, 71, 2482, (1949). c. A.R.H. Cole: J. Chem. Soc, 3807, (1954). d. A.R.H. Cole: J. Chem. Soc, 3810, (1954). 45. R.A. Baylouny and R. Jaret: Division of Organic Chemistry of the American Chemical Society, Abstracts of Papers Presented at the 149th Meeting of the American Chemical , Society, Abstract 51, 24P, (1965). 46a. R.T. LaLonde: J. Org. Chem., 27, 2275, (1962). b. R.T. LaLonde and L.S. Forney: J. Am. Chem. Soc, 85, 3767, (1963) . ~ ~ c. R.T. LaLonde and M.A. Tobias: J. Am. Chem. Soc, 85, 3771, (1963) . ~ \" d. R.T. LaLonde and J.J. Batelka: Tetrahedron Letters, 9, 445, (1964) . e. R.T. LaLonde and M.A. Tobias: J. Am. Chem. Soc, 86, 4068, (1964). 47. W.G. Dauben and R.L. Ca r g i l l : Tetrahedron, 15, 197, (1961). - 59 -48. H.G. Richey J r . and N.C. Buckley: J. Am. Chem. S o c , 85, 3057, (1963). 49. D.J. Cram and L.A. Singer: J. Am. Chem. Soc., 85, 1084, (1963)* i "@en . "Thesis/Dissertation"@en . "10.14288/1.0061954"@en . "eng"@en . "Chemistry"@en . "Vancouver : University of British Columbia Library"@en . "University of British Columbia"@en . "For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use."@en . "Graduate"@en . "Methylene addition to some 7-norbornadienyl derivatives"@en . "Text"@en . "http://hdl.handle.net/2429/38457"@en .