@prefix vivo: . @prefix edm: . @prefix ns0: . @prefix dcterms: . @prefix skos: . vivo:departmentOrSchool "Science, Faculty of"@en, "Chemistry, Department of"@en ; edm:dataProvider "DSpace"@en ; ns0:degreeCampus "UBCV"@en ; dcterms:creator "Hunter, David J."@en ; dcterms:issued "2010-01-21T22:41:32Z"@en, "1974"@en ; vivo:relatedDegree "Master of Science - MSc"@en ; ns0:degreeGrantor "University of British Columbia"@en ; dcterms:description """Remote oxidation at the C-5 position of isobornyl acetate (37) by chromium trioxide in glacial acetic acid/acetic anhydride, and the application of this oxidation to monoterpenes having the bicyclo[2.2.1] heptane framework is described. Subsequent conversion of 5- ketoisobornyl acetate (38) to 5-ketocamphene (42) and the relevance of this sequence to the proposed synthesis of the sesquiterpenes, culmorin (95), helminthosporol (99) and helmintho-sporal (97) is discussed. The oxidation of dihydroisocampherenyl acetate (87) at C-5 and subsequent conversion to b-ketodihyriro-p-santalene (90) is also described. The postulate that "certain compounds are susceptible to oxidation at positions remote from functionality" is further tested by the oxidation of fatty acid esters. The formation of a mixture of mono-ketoesters from the oxidation of methyl stearate (72;n=16), methyl docosanoate (72;n=20), methyl myristate (72;n=12), methyl palmitate (72;n=14), and methyl decanoate (72;n=8) by Cr03-Ac20/AcOH, and the procedure used to obtain a quantitative estimation of the relative amounts of isomeric ketoesters present in the product mixtures, is reported. Evidence is given for the validity of the analytical method used to estimate the relative amounts of isomeric ketoesters."""@en ; edm:aggregatedCHO "https://circle.library.ubc.ca/rest/handle/2429/18885?expand=metadata"@en ; skos:note "REMOTE OXIDATION OF NATURAL PRODUCTS By DAVID J . HUNTER B.Sc. Univers i ty of Leeds, England, 1972 A THESIS SUBMITTED'' IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n the Department of Chemistry We accept t h i s thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA September, 1974 In p resent ing t h i s t h e s i s in p a r t i a l f u l f i l m e n t o f the requirements f o r an advanced degree at the U n i v e r s i t y of B r i t i s h Columbia, I agree that the 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 reference and study. I f u r t h e r agree tha t permiss ion fo r e x t e n s i v e copying o f t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the Head of my Department or by h i s r e p r e s e n t a t i v e s . It i s understood that copying or p u b l i c a t i o n of t h i s t h e s i s f o r f i n a n c i a l ga in s h a l l not be a l lowed without my w r i t t e n p e r m i s s i o n . Department of The U n i v e r s i t y of B r i t i s h Columbia Vancouver 8, Canada Date - X I -ABSTRACT Remote oxidat ion at the C-5 pos i t i on of isobornyl acetate (37) by chromium t r i o x i d e i n g l a c i a l acet ic ac id /ace t i c anhydride, and the appl ica t ion of t h i s oxidat ion to monoterpenes having the b icyc lo [2 .2 .1 ] heptane framework i s described. Subsequent con-vers ion of 5- ketoisobornyl acetate (38) to 5-ketocamphene (42) and the relevance of th i s sequence to the proposed synthesis o f the sesquiterpenes, culmorin (95), helminthosporol (99) and helmintho-sporal (97) i s discussed. The oxidat ion of dihydroisocampherenyl acetate (87) at C-5 and subsequent conversion to b-ketodihyriro-p-santalene (90) i s also described. The postulate that \"ce r t a in compounds are suscept ible to oxidat ion at pos i t ions remote from func t iona l i t y \" i s further tested by the oxidat ion of fa t ty acid es ters . The formation of a mixture of mono-ketoesters from the oxidat ion of methyl stearate (72;n=16), methyl docosanoate (72;n=20), methyl myristate (72;n=12), methyl palmitate (72;n=14), and methyl decanoate (72;n=8) by Cr0 3 -Ac 2 0/AcOH, and the procedure used to obtain a quant i ta t ive estimation of the r e l a t i v e amounts o f isomeric ketoesters present i n the product mixtures, i s reported. Evidence i s given for the v a l i d i t y of the a n a l y t i c a l method used to estimate the r e l a t i v e amounts of isomeric ketoesters. TABLE OF CONTENTS Page Abstract • • • 1 1 Table o f Contents i i i L i s t of Figures i v Acknowledgements v i i Preface v i i i Introduction 1 Discussion 17 • Exper imen ta l . . . . -. ... • .75 Bibliography • • • 100 i v -LIST OF FIGURES Figure Page 1. Photo-oxidation of the C-14 ester 2. Photo-oxidation of the C-18 ester 3. Oxidation of Methyl Stearate [Data from the low reso lu t ion (15 eV) spectrum of acetals] 36 4. Oxidation of Methyl Stearate [Data from the low reso lu t ion (70 eV) spectrum of acetals] 37 5. Oxidation of Methyl Stearate [Data from low reso lu t ion (70 eV) spectrum of th ioaceta ls ] 38 6. Oxidation of Methyl Stearate [Data from high reso lu t ion (70 eV) spectrum of a c e t a l s ] . . 39 7. Oxidation of Methyl Docosanoate [Data from low reso lu t ion (15 eV) spectrum of th ioaceta ls] 40 8. Oxidat ion .of Methyl Docosanoate [Data from low reso lu t ion (70 eV) spectrum of th ioaceta ls] 41 9. Oxidation of Methyl Docosanoate [Data from low reso lu t ion (15 eV) spectrum of acetals] 42 10. Oxidation of Methyl Docosanoate [Data from high reso lu t ion (70 eV) spectrum of acetals] 43 11. Oxidation of Methyl Palmitate [Data from low reso lu t ion (70 eV) spectrum of a c e t a l s ] . . . . . . . 44 - V -12. Oxidation of Methyl Palmitate [Data from low reso lu t ion (70 eV) spectrum of t h i o a c e t a l s ] . . 45 13. Oxidation of Methyl Palmitate [Data from low reso lu t ion (15 eV) spectrum of acetals] 46 14. Oxidation of Methyl Myris ta te [Data from low reso lu t ion (15 eV) spectrum of th ioaceta ls] 47 15. Oxidation of Methyl Myris ta te [Data from low reso lu t ion (70 eV) spectrum of t h i o a c e t a l s ] . . . . . . . . . . . . . . . . 48 16. Oxidation of Methyl Myris ta te [Data from high reso lu t ion (70 eV) spectrum of a c e t a l s ] . . . . ' . 49 17. Oxidation of Methyl Decanoate [Data from low reso lu t ion (15 eV) spectrum of th ioaceta ls] 50 i o r i v i J n f 4 n . ~ £ i.u+u vi n m„4.„ — T AW. OJ-Uli V_i _i_ I'lC ^liy i L i W U O i l U a i . C ' IUO.L.CL X J. Will lUlV . reso lu t ion (70 eV) spectrum of t h i o a c e t a l s ] . . . . 51 19. Mass spectra l data from th ioace ta l of methyl 9- and 10- ketostearate 52 20. Mass spect ra l data from aceta l of methyl 9- and 10- k e t o s t e a r a t e . . . . . . . 53 21. Oxidation of Methyl Decanoate [Data from low reso lu t ion (15 eV) spectrum of th ioace ta l s , Frac t ion A J . . . . 54 22. Oxidation of Methyl Decanoate [Data from low reso lu t ion (70 eV) spectrum of th ioace ta l s , Frac t ion A ] . . . . 55 23. Oxidation of Methyl Decanoate [Data from high reso lu t ion (70 eV) spectrum of ace ta ls , Frac t ion A] 56 - v i -24. Oxidation of Methyl Decanoate [Data from low reso lu t ion (15 eV) spectrum of ace ta ls , Fract ion B ] . . . . . . . . 57 25. Oxidation o f Methyl Decanoate [Data from low reso lu t ion (70 eV) spectrum o f ace ta l s , Frac t ion Bj 58 26. Oxidation of Methyl Decanoate [Date from high reso lu t ion (70 eV) spectrum of ace ta l s , Frac t ion BJ 59 27. Oxidation of Methyl Decanoate [Data from low reso lu t ion (15 eV) spectrum of th ioace ta l s , Frac t ion B ] . 60 28. Oxidation of Methyl Decanoate [Data from low reso lu t ion (70 eV) spectrum of th ioace ta l s , Frac t ion B ] . . . . 61 29. Oxidation of Methyl Decanoate [Data from low reso lu t ion (15 eV) spectrum of ace ta l s , Frac t ion C] 62 30. Oxidation of. Methyl Decanoate [Data from low-reso lu t ion (70 eV) spectrum of ace ta ls , Frac t ion C ] . . . . . . . . 63 31. Oxidation o f Methyl Decanoate [Data from low reso lu t ion (15 eV) spectrum of th ioace ta l s , Frac t ion C ] . . . . 64 32. Oxidation of Methyl Decanoate [Data from low reso lu t ion (70 eV) spectrum of th ioace ta l s , Frac t ion C ] 6 5 33. Two hour oxidat ion of Methyl Decanoate [Data from low reso lu t ion (15 eV) spectrum of th ioaceta ls] 66 34. Two hour oxidat ion of Methyl Decanoate [Data from low reso lu t ion (70 eV) spectrum of th ioaceta ls ] 67 - V l l -ACKNOWLEDGEMENTS I wish to express my deepest grati tude to Dr. Thomas Money for h i s guidance and encouragement throughout the course of t h i s work. Grateful appreciat ion i s a l so extended to Dr. C. R. Eck for his suggestions and technica l advice, and to Dr. G. Eigendorf for useful discussions. A spec ia l expression of grat i tude i s due to Grace Wood who has aided so great ly with her excel lent typing assistance. v i i i -PREFACE Unless otherwise spec i f i ed the fol lowing are impl ied . Mel t ing points were determined on a Kofler apparatus and are un-corrected. Infrared spectra (TR) were recorded on a Perkin-Elmer model 137, spectrophotometer and ca l ib ra ted by means of the 1601 cm~* band of polystyrene. Nuclear magnetic resonance spectra (NMR) were recorded on a Var ian Associates model T-60 or Varian Associates model XL-100. Signal pos i t ions were reported on the T-sca le , with CCl^ as solvent and tetramethylsi lane as an in te rna l standard. Mass spectra were obtained on At las CH-4 and A . E . I . MS902 instruments. Microanalyses were performed by Mr. P. Borda, Microanalysis Laboratory, Univers i ty of B r i t i s h Columbia, Vancouver, B. C. Gas - l iqu id chromatography ( g . l . c . ) was ca r r i ed out on a Varian Aerograph, Model 90-P, using the fo l lowing columns. Length Stat ionary phase Support Mesh 10 f t x h i n . 3% SE 30 Varoport 30 100/120 Car r i e r gas (helium) flow rate was 60 ml/min. Solvents employed were e i ther Reagent grade or C e r t i f i e d grade. The term \"petroleum ether\" refers to the low b o i l i n g f rac t ion of C e r t i f i e d grade petroleum d i s t i l l a t e (b.p. ca . 3 0 - 6 0 ° ) . - i x -The fol lowing abbreviat ion have been made i n the presentat ion of NMR data. broad s broad s ing le t bd broad doublet d doublet dd doublet of doublets dq doublet of quartets m mul t ip l e t q quartet s s i n g l e t t t r i p l e t - 1 -INTRODUCTION Although many of the reactions which occur i n nature have analogies i n the laboratory there are others, notably those invo lv ing reg iospec i f i c oxidat ion of molecules at \"unreactive\" pos i t i ons , which are inaccess ible to the organic chemist. C la s s i c examples of reactions i n th i s l a t t e r category are the oxidat ion of s t ea r i c acid to o l e i c acid and the oxidat ion of terpenoids and s teroids at pos i t ions remote from other func t i ona l i t y . CH_(Cfl o ) ' ,C0 o H Mycobacterium ^ CH„(CH„)_CH = CH(CH_)_C0.H o i lb £ p h l e i •> ^ I z / z s tea r ic acid — o l e i c ac id Several laboratory techniques have been developed to achieve reg iospec i f ic func t iona l i za t ion of molecules at unreactive pos i t ions . The f ree - rad ica l chain decomposition of a C^g-N-chloroamine (Hofmann-LOffler-Freytag r e a c t i o n ) 1 to a p y r o l l i d i n e , as shown below, i s the f i r s t well-known example of reactions on \"nonactivated carbon atoms.\" In 1958 th i s method was used to func t iona l ize 18-methyl RCH2CH2CH2CH2NR'C1 + HCl R» 2 groups i n s teroids and the synthesis of dihydroconessine (2) by i r r a d i a t i o n of a s u l f u r i c ac id so lu t ion of 33-dimethylamino-20a-methylchloroaminoallopregnane (1) with u l t r a - v i o l e t l i g h t i s a s p e c i f i c example o f t h i s process. Cl) (2) - .3 -3 I t was postulated by Barton that photolysis of a l k y l n i t r i t e s might furnish excited alkoxy r ad ica l s with su f f i c i en t energy, i n excess of that found i n thermally generated r a d i c a l s , t o permit in te rna l hydrogen transfer according to scheme 1 (X = NO, Y = chain of carbon atoms). Later work showed that transformations of t h i s type take, place only when the chain of carbon atoms (Y) i s no more or no less than two, i e . one of the prerequis i tes for the \"Barton reac t ion\" i s the a v a i l a b i l i t y of a six-membered, c y c l i c t r a n s i t i o n s ta te . The react ion i s not l imi t ed to n i t r i t e s ; hypochlori tes (X = Cl) and hypoiodites (X = I) behave s i m i l a r l y . OX H OH I I I _ C — Y — C - • —C — Y i i i Scheme 1 The major app l i ca t ion of the Barton react ion has been i n the s te ro id f i e l d , where i t has been used to funct ional ise C-18 and C-19 methyl groups. Thus, photolysis of 38-acetoxy-5a-pregnan -20ct-yl n i t r i t e (3) i n benzene gave an isomeric oxime (4), 3B-acetoxycholestan-6g-yl n i t r i t e (5) on photolysis i n toluene gave the C19-nitros.o 3 dimer (6) which was r ead i ly converted to the corresponding oxime (7) . I r r ad ia t ion of c o r t i c o s t e r o n e - l l - n i t r i t e (8), followed by ni t rous ac id 4 treatment, gave aldosterone (10) . — C -5 -(8) CH2OAc OH CH^OAc (9) (10) Photolysis of simple a l i p h a t i c ketones i n saturated hydro-carbon solvents was found by Yang*' to lead to the formation of cyclobutanols e.g. i r r a d i a t i o n of 2-pentanone (11) i n cyclohexane gave acetone, ethylene and 1-methycyclobutanol (12). As i n the Barton reac t ion , t h i s photolysis involves the production of a CH, H R \\ • / 0 CH II \\ • C ^ CH C H 2 H hv CH 3C*V CH CH / C H 2 CH • -> 3 OH I C CH — R f I TH ' L M 2 ^ - C H 2 (11) (12) - 6 -react ive heteroatom r a d i c a l i n a molecule which then, by intramolecular attack on a hydrogen atom located s i x atoms away, i n i t i a t e s functiona-l i s a t i o n of a pos i t i on which i s not chemically act ivated i n the usual sense. I t has been shown^ that primary and secondary a l i p h a t i c alcohols containing unactivated — r .—(TH.\"* —-OH + — v - \" 2 ' 1 4 - x \" • 2 ' x Scheme 2 I t was suggested that i f the carbon chain was made longer the f l e x i b i l i t y of the system could resu l t i n a less regio-spec i f i c react ion and i t was also suggested that the absence of attack on the methyl group was the resu l t of the.chemical s e l e c t i v i t y of the benzophenone t r i p l e t , since the methyl hydrogens are less react ive than are methylene hydrogens. - 10 -0 8 9 10 11 12 13 14 Si tes of Oxidation Figure 1. Photo-oxidation of the C... ester . 0 2 ~To\"- 11 l l 13 \"TV\"!? 16\" 17 18 Si tes of Oxidation - 11 -This method of se lec t ive func t iona l i za t ion has also been applied to s te ro ids . Thus, i r r a d i a t i o n of the benzophenone-4-propionic 15 14 ester of cholestan-3a-ol (19) i n benzene gave A -cholest-3a-enol (20) as the only unsaturated s te ro id product. The carbonyl oxygen of the benzophenone t r i p l e t removes the hydrogen at C-14 and the carbon atom of the benzophenone t r i p l e t then removes a neighbouring hydrogen at C-15. The same d i r a d i c a l also undergoes some col lapse , forming a new carbon-carbon bond at C-14 to give (21). In add i t ion , there i s attack at C-12 and C-7 with subsequent coupling to give the alcohols which can be dehydrated by cleavage with ruthenium te t ra -oxide and sodium periodate to 12-ketocholestan-3a-ol (22) and 7-ketocholestan-3ot-ol (23). (21) - 12 -(19) (23) I r r ad ia t ion of the benzophenoneacetic ac id ester of cholestan-13 3 OXIDATION of METHYL DECANOATE [Data from low reso lu t ion ( 1 5 eV) spectrum of th ioaceta ls (78; x+y=7): -x x- based on fragment (79b) - o — o - based on fragment (80b)]. - 51 -3 4 5 6 7 8 9 Si tes of Oxidat ion OXIDATION of METHYL DECANOATE [Data from' low r e s o l u t i o n (70 eV) . spectrum of th ioace ta l s (78; x+y=7): -x x - based on fragment (79b) -o o- based on fragment (80b)]. - 52 -C H 3 ( C H 2 ) x s s\" Sites of Relat ive % D i s t r i b u t i o n Oxidation Intensi ty HIGH RESOLUTION 9(x=8) 70.8 10(x=7) 70.1 50.2% 49.8% LOW RESOLUTION AT 15 eV 9(x=8) 1.10 47.8% I0(x=7) 1.20 52.2% LOW RESOLUTION AT 70 eV 9(x=8) 11.65 51.0% 10(x=7) 11.20 49.0% +S S ( C H 2 ) y C0 2CH 3 Si tes of Rela t ive \\ Oxidation Intensi ty HIGH RESOLUTION 9(y=7) 58.6 10(y=8j 50.8 D i s t r i b u t i o n 53.5% 46.5% LOW RESOLUTION AT 15 eV 9(y=7) 1.15 51.2% 10(y =S) 1.10 LOW RESOLUTION AT 70 eV 9(x=7) 12.00 51.4% 10(y=8) 11.35 48.6% F i g . 19 Mass spect ra l data from th ioace ta l of methyl 9- and 10- ketostearate - 53 -I \\ 0 0 + C H 3 ( C H 2 ) X - C Si tes of Rela t ive % D i s t r i b u t i o n Oxidation Intensi ty HIGH RESOLUTION 9(x=8) 26.7 48.5% 10(x=7) 28.3 51.5% LOW RESOLUTION AT 15 eV 9Cx=8) 1.10 52.4% n nn ± , uu LOW RESOLUTION AT 70 eV 9(x=8) 11.45 48.8% 10(x=7) 12.00 51.2% I 1 C —(CH 2 ) C0 2 CH 3 Si tes of Relat ive % D i s t r i b u t i o n Oxidation In tens i ty HIGH RESOLUTION 9(y=7) 19.8 48.0% 10(y=8) 21.4 52.0% LOW RESOLUTION AT 15 eV 9(y=7) 1.10 48.8% I i n r Q-\\ \" - V 1 1 C LOW RESOLUTION AT 70 eV 9(y=7) 11.00 48.5% 10(x=8) 11.65 51.5% F i g . 20 Mass spect ra l data from acetal of methyl 9-and 10- ketostearate 2 3 4 5 6 7 8 Si tes of Oxidation F i g . 21. OXIDATION of METHYL DECANOATE [Data from low reso lu t ion (15 eV) spectrum of th ioaceta ls (78; x+y=7) [FRACTION A ] : -x x- based on fragment (79b): -o o- based on fragment (80b)]. - 55 -40 t 30 20 H o •H « J •M H OT •H Q 10 Sites of Oxidation Fig. 22. OXIDATION of METHYL DECANOATE [Data from low resolution (70 eV) spectrum of thioacetals (78; x+y=7) [Fraction A]: -x-—x- based on fragment (79b): - o — o - based on fragment (80b)]. - 56 Si tes of Oxidation F i g . 23. OXIDATION of METHYL DECANOATE [Data from high r e so lu t ion (70 eV) spectrum of acetals (77; x+y=7) [Fract ion A] : - x — x - based on \" fragment (79a): - o — o - based on fragment (80a)]. 40 - 57 -2 3 4 5 6 7 8 9 Si tes of Oxidation F i g . 24. OXIDATION of METHYL DECANOATE [Data from low reso lu t ion (15 eV) spectrum of acetals (77; x+y=7) [FRACTION B ] : -x x- based on fragment (79a); - o — o - based on fragment (80a)]. - 58 S i tes of Oxidat ion F i g . 25 OXIDATION of METHYL DECANOATE [Data from low r e so lu t i on (70 eV) spectrum of aceta ls (77; x+y=7) [Frac t ion B ] : - x — x - based on fragment (79a): -o o- based on fragment (80a)]. - 59 -40 30 20 J3 O •H •P 3 .o •p tn 10 _0_ 2 3 4 5 6 7 8 9 S i t e s o f O x i d a t i o n F i g . 26. OXIDATION o f METHYL DECANOATE [Data f r o m h i g h r e s o l u t i o n (70 eV) spectrum o f a c e t a l s (77;x+y=7) [ F r a c t i o n B ] : - x — x - b a s e d on frag m e n t (79a): -o o- b a s e d on fragment ( 8 0 a ) ] . Si tes of Oxidation OXIDATION of METHYL DECANOATE [Data from low reso lu t ion CIS eV) spectrum of th ioaceta ls (78; x+y=7) [FRACTION B ] : - x — x - based fragment (79b): -o o- based on fragment (80b)]. 40 - 6 1 -X Sites of Oxidation Fig. 28. OXIDATION of METHYL DECANOATE [Data from low resolution (70 eV) ' spectrum of thioacetals (78; x+y=7) [Fraction B]: - x — x - based on fragment (79b); - o — o - based on fragment (80b)]. - 62 -4 5 8 ? 8 9 Si tes of Oxidation OXIDATION of METHYL DECANOATE [Data from low reso lu t ion ( 1 5 eV) spectrum of acetals (77; x+y=7) [FRACTION C ] : -x x - based on fragment (79a): -o o- based on fragment (80a)]. - 63 -2 3 4 5 6 7 8 Sites of Oxidation Fig. 30. OXIDATION of METHYL DECANOATE [Data from low resolution (70 eV) spectrum of acetals (77; x+y=7) [FRACTION C]: - x — x - based on fragment (79a): - o — o - based on fragment (90a)]. 100 6 4 -o-x o X -O. 2 3 4 5 6 7 8 Si tes of Oxidation F i g . 31: OXIDATION of METHYL DECANOATE [Data from low reso lu t ion CIS eV) spectrum of th ioaceta ls (78; x+y=7) [FRACTION C] : -x x - based on fragment (79b): -o o- based on fragment (80b)]. Sites of Oxidation Fig, 32. OXIDATION of METHYL DECANOATE [Data from low resoltuion (70 eV) spectrum of thioacetals (78;x+y=7) [Fraction C] ; - x — x - based on fragment (79b): - o — o - based on fragment (80b)]. - 66 -^ * : : : 9. 2 3 4 5 6 7 8 9 Site of Oxidation Fig. 33. TWO HOUR OXIDATION of METHYL DECANOATE [Data from low resolution (15 eV) spectrum of thioacetals (78;x+y=7): -x x- based on fragment (79b): - o — o - based on fragment (80b)]. - 67 -40 30 20 c o 3 Xi •H u •p tn •H a 10 2 3 4 5 6 . 7 Sites of Oxidation Fig. 34. TWO HOUR OXIDATION of METHYL DECANOATE [Data from low resolution (70 eV) spectrum of thioacetals (78;x+y=7): - x — x based on fragment (79b): - o — o - based on fragment (80b)]. - 68 -3. Remote Oxidation of Sesquiterpenes In e a r l i e r inves t iga t ions of monoterpene acetates i t was demonstrated that isobornyl acetate (37) could be converted to the 5-keto der iva t ive and that the l a t t e r compound could then be rearranged to 5-ketocamphene (42) (40) (42) This react ion sequence forms the basis of current studies i n the sesquiterpene area and i n an i n i t i a l i nves t iga t ion i t was demonstrated that dihydroisocampherenyl acetate (87) could be trans-formed i n a s i m i l a r fashion to 5-ketodihydro -B-santalene (90) [Scheme 4 ] . Campherenone (84) was treated with 10% Pd-C and hydrogen to give dihydrocampherenone (85) which provided dihydroisocampherenol (86) on reduction with l i t h ium aluminium hydride. Dihydroisocampher-enol (86) i n pyr id ine and ace t ic anhydride was heated at 90°C for - 69 -24 hours to give;, after chromatography over aluminium oxide (neutral Grade IV) , dihydroisocampherenyl acetate (87) as a colourless o i l . Appl ica t ion of the usual oxidat ion conditions (cf . p 19) to dihydroisocampherenyl acetate (87) provided l i t t l e or no product after several days. However, when chromyl acetate was added, i n the usual fashion, to dihydroisocampherenyl acetate (87) i n g l a c i a i ace t ic ac id /ace t ic anhydride and the so lu t ion heated at 90°C for Scheme 4 1 hour, the product was a mixture of s t a r t i ng material (10%) and one product (90%). Column chromatography of the mixture over aluminium oxide (neutral Grade IV) gave, by e lu t i on with pentane, 5-ketodihydro-- 70 -isocampherenyl acetate (88) i n ca. 25% y i e l d . The infrared spectrum of (88) showed absorption bands at 1745, 1730 and 1240 cm\" 1 . The NMR spectrum of 5-ketodihydroisocampherenyl acetate (88) showed resonances at r 9.18 (s, 3H, t e r t i a r y methyl), 9.16 (s , 3H, t e r t i a r y methyl), 8.06 (s, 3H, acetate methyl), 7.67 ( m, 3H, -CH_2C0-, bridgehead H) and 5.36 (dd, IH, -CHOAc). In add i t ion , the expected molecular ion peak at m/e 280 was observed i n the mass spectrum. Hydrolysis and rearrangement of 5-ketodihydroisocampherenyl acetate (88), as for 5-ketoisobornyl acetate (38) (cf . p .20) , gave 5-ketodihydro-B-santalene (90). The infrared spectrum of (90) showed absorption bands at 1735, 1660 and 880 c m - 1 . The NMR spectrum of 5-ketodihydro-S-santalene (90) showed resonances at T 8.94 (s, 3H, t e r t i a r y methyl). 7;68 ( t , ?H - CH^m-), 7,32 (broad s, IH, \" H y l i c bridgehead H) and 5.43 (d, 2H, CH^ = J • I n add i t ion , the expected molecular ion peak at m/e 220 was observed i n the mass spectrum. The app l i ca t ion of the oxidat ion procedure described above to i so longibornyl acetate (92) could provide a simple synthet ic route to 35 culmorin (95). Isolongibornyl acetate (92) has been oxidised with chromyl acetate, CrO^-A^O, and the product i s a mixture of s t a r t i ng material and two isomeric keto-acetates whose structures remain to be determined. The helminthosporanes are a group of sesquiterpenes elaborated - 71 -(91) ; (92) OH . (93) (94) (95) 36 by Helminthosporium sativum and H. v i c t o r i a e . In the o r i g i n a l reports heiminthosporal (98) and helminthosporol (100) were i so la t ed from H. sativum but subsequent inves t iga t ions indicated that these are artefacts derived from the true metabolites, prehelmin-thosporal (97) and prehelminthosporol (99). A s t r u c t u r a l l y re la ted sesquiterpene a l k a l o i d , v i c tox in ine (101) has been i so l a t ed from the 37 cul ture f i l t r a t e of H. v i c t o r i a e . Heiminthosporal (98) i s a t o x i n , which along wi th the fungus, i s responsible for widespread seedling b l i g h t , foot and root ro t and l ea f spot of cereals . One reason for the attempted synthesis of (46) and (48) (cf. p. 23) , the monoterpene analogues of heiminthosporal (98) and helminthosporol (100), was the hope that these monoterpenes might prove to be an t i t ox ins . - l i -lt has been suggested that sativene (102) could be the b i o l o g i c a l precursor of prehelminthosporal (97) and preheiminthosporol (99), and ce r t a in ly the co-occurrence of these compounds would tend to support t h i s postulate . While the cleavage of the appropriate bond i n sativene may be poss ible i n an enzyme catalysed react ion there i s no laboratory precedent for such a process and a synthetic approach based on th i s b iosynthet ic proposal presents considerable problems. However, i f a su i tab le de r iva t ive o f sativene i s considered as a synthet ic intermediate the C-C bond cleavage becomes more reasonable. Many der iva t ives are of course poss ib le but i t was considered that ketosativene (103) might be admirably su i ted to i t s ro l e as a synthet ic precursor of heiminthosporal and de r iva t ives . The i n t i t i a l ob jec t ive , therefore, i s the development o f a s tereospeci f ic synthesis of ketosativene (105) and one of the approaches under consideration involves adaption of the sequence of reactions 19 (Scheme 5) developed for the synthesis of sat ivene. C l e a r l y , the key reac t ion i n the proposed route to ketosativene (103) would be to introduce oxygen func t iona l i ty in to the 5-posi t ion of i so longibornyl acetate (106) and the p o s s i b i l i t y of accomplishing th i s by d i r ec t oxidat ion wi th CrO^-Ae^O/AcOH i s being inves t igated. The oxidat ion of isobornyl acetate (37) and of dihydroiso-campherenyl acetate (87) at the 5-pos i t ion wi th chromyl acetate i n - 74 -g l a c i a l acet ic ac id suggests that the d i r ec t oxidat ion of isoylango-bornyl acetate (106) may be poss ib le . I n i t i a l studies have shown that isoylangobornyl acetate (106) i s indeed oxidised by chromyl acetate i n g l a c i a l acet ic ac id . However, isoylangobornyl acetate appears to be extremely susceptible to oxidat ion (oxidat ion i s complete wi th in a matter of hours at room temperature) and the product i s a mixture of a number of compounds. Studies are continuing i n t h i s area i n an attempt to character ize the products and to increase the s e l e c t i v i t y of the oxidat ion process, poss ib ly by carrying out the react ion at low temperature and/or by various solvent e f fec ts . - 75 -EXPERIMENTAL , 5-Ketoisobornyl acetate (38) Chromium t r i o x i d e (90 g.) was ca re fu l ly added to ace t ic anhydride (145 ml.) cooled i n an ice-ba th . The r e su l t i ng so lu t ion was added dropwise over a period of two days to an i c e - c o l d so lu t ion of i sobornyl acetate (37) (66 g . , 0.314 moles) i n g l a c i a l ace t i c acid (280 ml) and acet ic anhydride (125 ml.) and af ter 8 days at room temperature saturated sodium bicarbonate so lu t ion was caut iously added tc the reac t ion mixture. Excess ace t ic anhydride was removed under reduced pressure and the r e s u l t i n g green so lu t ion extracted with ether (4 x 200 ml) . The combined extracts were washed successively with 5% sodium hydroxide, saturated sodium bicarbonate so lu t ion and water. Af ter drying (anhydrous sodium s u l f a t e ) , removal of solvent provided a pale yellow o i l (53 g.) which was shown by g . l . c . (3% SE 30) to consis t of 5-ketoisobornyl acetate (38) (59%), isobornyl acetate (37) (34%) ancTcamphor (39) (6%). The y i e l d of product based on consumed s t a r t i ng mater ia l was 66%. F rac t iona l d i s t i l l a t i o n of the o crude o i l provided pure 5-ketoisobornyl acetate (38), b .p . 108-114 (1.0 mm): v (CC1J 1750, 1385, 1365, 1420, 1230 cm\" 1 , T (CC1., 60 MHz) max 4 . • • v 4 J 9.23 (s , 3H, C H 3 _ ) , 9.14 (s, 3H, CH_3_), 8.97 (s, 3H, CH_ 3-), 8.08 (s, 3H, CH 3 C0 2 _) , 5.26, (dd, IH, - CHOAc); m/e 210 (M+) - 76 -5-Ketoisobomeol (40) 5-ketoisobornyl acetate (38) (9g. , 0.043 moles) was treated i -with a so lu t ion of sodium carbonate (6 g.) i n water (150 ml) and methanol (90 ml.) for 48 hours at 40-50° C. After coo l ing , the reac t ion mixture was extracted wi th ether (4 x 150 ml . ) and the combined extracts dr ied (anhydrous sodium su l f a t e ) . Removal of solvent provided a white s o l i d (6.9 g, 95%) which was r e c r y s t a l l i z e d from benzene-petroleum ether to give pure 5-ketoisoborneol (m.p. 142-144°) . v (CC1,) 3490, 1745, 1410, 1385, 1365 c m - 1 ; T ( C C 1 , , 60 MHz) max 4 4 9:31 (s, 3H, CH 3 _) , 9.19 (s , 3H, C H ^ ) , 9.09 (s, 3H, CH-) , 6.70 (dd, IH, - CHOH), 5.51 (broad s, IH , - OH); m/e 168 (M + ) . Ana l . Calcd. for C - . H ^ O . : C, 70.42; H, 9.53. Found: C, 70.33; H, 9.63. 5-Ketocamphor (41) Jones' reagent (CrO^-H^O^-^O) was added dropwise to 5-ketoisoborneol (40) (160 mg., 0.001 moles) i n acetone (15 ml . ) u n t i l oxidat ion was complete._ Removal of acetone under reduced pressure and work up i n the usual way provided 5-ketocamphor (41) as a white s o l i d (135 mg., 85%) m.p. 209-211° (from pet. e ther) . Vmax ( C C V 1 7 5 0 ' 1 3 8 5 ' 1 3 6 5 c m ~ 1 , T ( C C 14> 6 0 fflz) 9.05 (s, 3H, C H 3 - ) , 9.00 (s , 3H, C H 3 - ) , 8.95 (s , 3H, CH_ 3-). - 77 -5-Ketocamphene (42). Methanesulfonyl chlor ide (15 g . , 0.013 moles) was added to a so lu t ion of 5-ketoisoborneol (40) (7 g . , 0.029 moles) i n pyr id ine (315 ml.) and the reac t ion mixture was s t i r r e d , under n i t rogen, at 90-95° for 24 hours. After coo l ing , the so lu t ion was d i l u t ed with water and extracted with ether (4 x 150 m l . ) . The combined extracts were washed with d i l u t e hydrochlor ic a c i d , saturated sodium chlor ide so lu t ion , and dr ied (anhydrous sodium su l f a t e ) . Removal of solvent provided a dark coloured o i l (6.2 g.) which was shown by g . I . e . to be a mixture of two components (approximate r a t i o 3:1) . Column chromatography of the mixture over aluminium oxide (neutral Grade IV) gave, by e lu t ion with pet. ether, 2.7 g. of 5-ketocamphene (42) (62%) and 0 . 8 g. of a mixture o f the two components. Further chroma-tography provided a pure sample of the minor component (43). 5-ketocamphene exhibi ted the fol lowing cha rac t e r i s t i c s : v (CC1.) 3050, 1745, 1650, 890 cm\" 1 , x (CC1., 60 MHz) 8.98 (s, 3H, max 4 v 4 \" ' V ' ' C H 3 - ) , 8.89 (s, 3H, C H 3 - ) , 8.4-7.6 (m, 5H), 6.95 (broad s, IH, a l l y l i c bridgehead H) , 5.12 (d, 2H, J=13 Hz; CH_2= ) ; m/e 150 (M+) : The minor component exhibi ted cha rac te r i s t i c s consistent with those of 3-ketotr icyclene (43). v (CC1.) 1745, 1385, 1365 cm\" 1 J v . • max v 4' ' ' x ( C C l 4 , 60 MHz) 9.07 (s , 3H, CH_ 3-), 9.03 (s, 3H, CH 3 -) 8.83 (s , 3H, - 78 -5-Ketocamphene hydrochloride (52) Anhydrous calcium chlor ide (22 g.) was added to a so lu t i on of 5-ketocamphene (42) (1.1 g . , 0.073 moles) i n ether (88 ml ) . The mixture was cooled i n an ice-bath and dry hydrogen chlor ide bubbled through the mixture for 3 hours. After 3 days at room temperature the so lu t ion was f i l t e r e d and the ether extracts washed with saturated sodium bicarbonate s o l u t i o n , saturated sodium chlor ide s o l u t i o n , and dr ied (anhydrous sodium su l f a t e ) . Removal of solvent provided 5-ketocamphene hydrochloride (52) as a white s o l i d (800 mg., 65%) m.p. 149-153° (from methanol) v x (CC14) 1750, 1385, 1365 cm\" 1 ; T (CC1 4,.60'MHZ) 9.00 (s, 3H, CH_ 3-), 8.72 (s, 3H, Cti^-), 8.36 Anal . Calcd. for C 1 Q H 0C1: . C, 64.34; H, 8.03; C l , 19.04. Found: C, 64.22; H, 7.88; C l , 19.15. 6-bromo-5-ketocamphene (53) Butyl l i t h ium (2 m l . , 2 mmoles) was added to a so lu t ion of 5-ketocamphene (42) (300 mg., 2 moles) and dicyclohexylamine (380 mg., 2 mmoles) i n tetrahydrofuran (2 ml) under ni t rogen. After 15 minutes at room temperature, bromine (320 mg, 2 mmoles)in methylene chlor ide - 79 -(1 ml.) was added at -78°C. After one minute, the so lu t ion was quenched with saturated sodium bicarbonate so lu t ion and extracted with pet. ether (3x). The combined extracts were washed with saturated sodium bicarbonate so lu t ion and saturated sodium chlor ide so lu t ion . After drying (anhydrous sodium s u l f a t e ) , removal of solvent provided a yellow o i l (335 mg.) which was shown by g . l . c . (3% SE 30) to be a mixture of s t a r t i ng mater ia l and one product (approximate r a t i o 1:4). Column chromatography of the mixture over aluminium oxide (neutral Grade I) gave, by e lu t ion with pet . ether, 6-bromo-5-ketocamphene (53) (230 mg, 50%). v (CC1.) 1745, 1650, 895 cm\" 1 , T (CC1„, 60 MHz) 8.85 max K AJ K 4 (s , 5H, C H , - ) , 8.75 (s, 3K, CH^-) , 7.70 (m, 311)., 6.73 (broad s, IH, bridgehead), 6.53 (d, IH, J=10 Hz, endo-CHBr-), 6.20 (d, IH, J=3Hz, exo-CHBr-), 4.87 (d, 2H, J=14 Hz, OLy' = .-) - 80 -Oxidation of fenchyl acetate (-54) Chromium t r i o x i d e (7 g.) was ca re fu l ly added to ace t ic anhydride (11.ml.) and the r e su l t i ng s o l u t i o n added dropwise over a * period of one day to a cold mixture of fenchyl acetate (54) (5 g, 0.025 moles) i n g l a c i a l ace t ic ac id (20 ml) and ace t ic anhydride (9 m l . ) . After 4 days at room temperature saturated sodium bicarbonate so lu t ion was added caut iously to the reac t ion mixture. Excess ace t ic anhydride was removed under reduced pressure and the r e s u l t i n g green so lu t ion extracted wi th ether (4 x 100 m l . ) . The combined extracts were washed successively wi th 5% sodium hydroxide., saturated sodium bicarbonate so lu t ion and water. After drying (anhydrous sodium s u l f a t e ) , removal of solvent provided a colourless o i l (3.5 g. 65%) which exhibi ted two peaks, i n the approximate r a t i o 3 :1 , on g . l . c . (3% SE 30, 140° , re tent ion times 4.6 and 7 minutes). v (CC1.) 1750 (broad), 1240 c m - 1 , max 4 * The n.m.r . spectra of fenchyl acetate (54) ind ica ted that i t consisted of a mixture of exo and endo acetates i n the approximate r a t i o 5:3. - 81 -5- and 6- ketofenchol (56a,b) A mixture of 5- and 6- ketofenchyl acetate (55a,b) (1 g , 0.0042 moles) was treated wi th a so lu t ion of sodium bicarbonate (0.7 g) i n water (17 ml.) and methanol (10 ml) for 3 days at 40-50°C. After coo l ing , the reac t ion mixture was extracted with ether (4 x) and the combined extracts dr ied (anhydrous sodium su l f a t e ) . Removal of solvent provided a colourless o i l (700 mg, 85%). v ( C C 1 J 3500, 1745, 1380, 1360 cm\" 1 , max v 4 5- and 6-ketofenchone (57,58) Jones' reagent (CrO^-H^SO^-^G) was added dropwise to a mixture of 5- and 6-ketofenchol (56a,b) (700 mg., 0.0041 moles) i n acetone (50 ml.) u n t i l oxidat ion was complete. Removal of acetone under reduced pressure and work up i n the usual way provided a colourless o i l (630 mg, 90%) which exhibi ted two peaks, i n the approximate r a t i o 3 :1 , on g . l . c . (3% SE 30, 140°, re tent ion times 2.0 and 2.8 minutes). Column chromatography of the mixture over aluminium oxide (neutral Grade I) gave, by e lu t ion with pet. ether, a pure sample of each component. The major component exhibi ted cha rac te r i s t i c s consistent with those of 5-ketofenchone (57). v ( C C 1 J 1750, 1380, 1360 *• . max 4' cm\" 1 , x (CC1 4 , 100 MHz) 9.04 (s, 3H, CH_3~), 8.92 (s, 3H, CH_3~), - 82 -8.82 (s, 3H, CH_ 3-), 8.04 (m, 4H), 7.56 (broad s, IH, bridgehead). The minor component exhibi ted cha rac te r i s t i c s consistent with those of 6-ketofenchone (58). v (CCTJ 1750, 1385, 1365 ^ 3 max 4 c m - 1 x (CC1 4 , 100 Mz) 9.05 (s, 3H, CH_ 3-), 8.98 (s , 3H, CH_ 3-), 8.95 (s, 3H, CH_ 3-), 8.02 (s , IH, bridgehead), 7.86 ( t , 2H), 7.58 ( t , 2H). Oxidation of (-)-fenchone (62) Chromium t r i o x i d e (7 g.) was ca re fu l ly added to ace t i c anhydride (11 ml.) and.the r e s u l t i n g so lu t ion added dropwise over a period of one day to a cold mixture of (-)-fenchone (62) (5 g . , 0.033 moles) i n g l a c i a l acet ic acid (20 ml) and ace t ic anhydride (9 m l . ) . After 3 days at room temperature, work up, as described for fenchyl acetate (cf . p . 80) provided a colourless o i l (1.24 g . , 23%). G . l . c . analysis (3% SE 30) indicated a 1:1 mixture of 5-and 6-ketofenchone (57,58) plus several minor products which were -not character ized. v (CC1.) 1750, 1385, 1365 cm\" 1 , max v 4 Oxidation of methyl stearate (72; n=16) Chromium t r i o x i d e (7 g.) was ca re fu l ly added to ace t i c anhydride (11 ml) and the r e su l t i ng so lu t ion added dropwise over a period of one hour to a cold mixture o f methyl stearate (72; n=16) - 83 -(5 g . , 0.017 moles) i n g l a c i a l acet ic acid (20 ml.) and ace t ic anhydride (9 m l . ) . After 24 hours at room temperature saturated sodium bicarbonate so lu t ion was caut iously added to the react ion mixture. Excess acet ic anhydride was removed under reduced pressure and the r e su l t i ng green so lu t ion extracted with ether (4 x 100 m l . ) . The combined extracts were washed successively wi th 5% sodium hydroxide, saturated sodium bicarbonate so lu t i on and water. After drying (anhydrous sodium su l f a t e ) , removal of solvent provided a c r y s t a l l i n e s o l i d (4*5 g.) which was shown by g . l . c . (3% SE 30) to consis t of methyl stearate (50%) and a mixture of methy ketostearates (50%) (unresolved on g . l . c ) . Careful column chromatography of the mixture over s i l i c a gel gave, by e lu t ion with pet. ether/ether (98:2), a pure mixture o f methyl ketostearates (73; x+y=15) (1.9 g . , 65% based on consumed s t a r t i ng ma te r i a l ) . m a x (CC1 4 ) : 1750, 1720 cm\" 1 : (CC1 4 > 100 MHz) 9.07 ( t , 3H, C H 3 - ( C H 2 ) n ) , 8.75, 8.45 (broad s, m, 24 H, C H 3 - (CH_2) n ) , 7.73 0 (3 overlapping t r i p l e t s , 6H, CH 2 C0 2 CH 3 , -CH^C-CJHy, 6.40 (s , 3H, - C O 2 C H 3 ) . Ana l . Calcd. for C i n H , , 0 7 : C, 73.07; H, 11.54. Found: i y 3D O C, 72.91; H, 11.60. ~ - 84 -Methyl hydroxystearates (75) Sodium borohydride (50 mg.) i n water... (1 ml.) was added dropwise to a so lu t ion of methyl ketostearates (73;x+y=15) (56 mg. 0.0002 moles) i n methanol (3 ml.) After 2-1/2 hours at room temperature, excess sodium borohydride was destroyed by the addi t ion of d i l u t e hydrochloric acid and the so lu t ion extracted with ether (3x). The combined extracts were washed with saturated sodium chlor ide so lu t ion and, after drying (anhydrous sodium su l f a t e ) , removal of solvent provided a quant i ta t ive y i e l d of a c lear o i l (56 mg.) which c r y s t a l l i z e d on standing. Vmax ( C C V 3 4 0 0 > 1 7 4 0 c m _ 1 ; T ( C C 1 4> 6 0 m z ' 9 - 1 4 (*» 3 H > C H 3 - ( C H 2 ) n ) , 8.72 (broad s, 28H, CH 3 - ( a y ) , 7.80 (m, 3H, -Methyl acetoxystearates (74) Methyl hydroxystearates (75) (125 mg., 0.0004 moles) i n pyr id ine (4 ml.) and acet ic anhydride (0.75 ml.) was heated at 80° for 24 hours. Af ter cool ing the so lu t i on was d i l u t ed with water and extracted with ether (3x). The combined extracts were washed with d i l u t e hydrochloric a c i d , saturated sodium chlor ide s o l u t i o n , and dr ied (anhydrous sodium su l f a t e ) . Removal of solvent provided a mixture of methyl acetoxystearates (74) (116 mg. 92%). vmax ( C C V 1 7 5 0 , 1 2 4 0 C m ~ 1 ; T ( C G 1 4 ' 1 0 0 m Z j 9 , 1 2 m > CH 3 - ( C H 2 ) n ) , 8.74 (broad s, 28H, CH 3 - (CH_ 2 ) 1 4 ) , 8.05 (s, 3H, -- 0 2 CCH 3 ) , 7.78 ( t , 2H, - CH_ 2C0 2CH 3), 6.40 (s, 3H, - C 0 2 C H 3 ) , 5.20 (m, IH, CHOAc). - 8 5 -Methyl octodecenoate (76) A mixture of methyl hydroxystearates (75) (650 mg., 0.002 moles) i n benzene (26 ml.) was treated with p-toluene su l fon ic ac id (350 mg.) at r e f lux i n a Dean-Stark apparatus for two days. After coo l ing , saturated sodium bicarbonate so lu t ion was added and the so lu t ion extracted with ether (3x). After drying (anhydrous sodium su l f a t e ) , removal of solvent gave an orange o i l (560 mg., 90%). v (CC1J 1750, 1660, 725 cm\" 1 , x (CC1., 60 MHz) 9.10 max 4 v 4 ( t , 3H, C H 3 - ( C H 2 ) n ) , 8.72, 8.10 (broad s, m, 26H, CH 3 (CH_ 2 ) 1 3 ) , 7.60 (m, 2H, - CH_2C02Me), 6.40 (s, 3H, - C0 2CH_ 3), 4.63 (broad s, 2H, - CH=CH-)> m/e 296 (M + ) . Methyl ketostearate acetals (77;x+y=15) Ethyl orthoformate (2 m l . ) , ethylene g l y c o l (1 ml) and p-toluenesulfonic ac id (5 mg.) were added to methyl ketostearate (100 mg.). After 1 hour at 90° , the so lu t ion was heated at 150° for 2 hours while excess ethyl orthoformate d i s t i l l e d of f . After coo l ing , saturated sodium bicarbonate so lu t ion was added and the so lu t ion extracted with ether (3x). The combined extracts were washed with saturated sodium chlor ide so lu t i on . After drying (anhydro sodium su l f a t e ) , removal of solvent .provided a quant i ta t ive y i e l d of acetals (77,x+y=15). - 86 \" v (CC1J 1745, 1150 cm\" 1 , T (CC1., 100 MHz) 9.12 ( t , 3H, max 4 4 C H 3 - ( C H 2 ) n ) , 8.76, 8.48 (broad s, m, 28H, C H 3 - (CH_2) 1 4 ) , 7.77 ( t , 2H, J=7Hz, - CH 2 C0 2 CH 3 ) , 6.40 (s, 3H, -C0 2CH ) , 6.18 (s, 4H, - OCH^CJ^O-) . Methyl ketostearate th ioaceta ls (78,x+y=15j Methyl ketostearate (73) (100 mg.) and ethanedi thiol (0.25 ml.) i n g l a c i a l ace t ic acid (3.2 ml.) were warmed to 50° and boron t r i f l u o r i d e etherate (0.25 ml.) added. After 3 hours at room temperature, the so lu t ion was d i l u t ed with water and extracted with ether (3x). The combined extracts were washed with saturated sodium bicarbonate so lu t ion and saturated sodium chlor ide so lu t i on . After drying (anhydrous sodium s u l f a t e ) , removal of solvent provided a quant i ta t ive y i e i d of th ioaceta ls (78,x+y-15). v (CC1J 1745 cm\" 1 x (CC1„, 100 MHz) 9.14 ( t , 3H, CH_-max v 4 v 4 v —3 ( C H 2 ) n ) , 8.74, 8.48 (broad s, m, 28H, CH 3 -(CH 2 ) ) , 7.80 ( t , 2H, -CH 2 C0 2 CH 3 ) , 6.82 (s, 4H, - SCH^CH^S-), 6.43 (s, 3H, - C O ^ H ^ ) . Oxidation of methyl myristate (72:n=12) Chromium t r i o x i d e (8 g.) was ca re fu l ly added to ace t ic anhydride (14 ml) arid the r e su l t i ng so lu t ion was added dropwise over a period of one hour to a cold mixture o f methyl myristate (72; n=12) (5 g . , 0.020 moles) i n g l a c i a l ace t ic acid (24 ml.) and acet ic anhydride (10 m l . ) . After 24 hours at room temperature, work up, as described for methyl stearate (cf . p . 8 2 ) , provided a green o i l (4.6 g.) - 87 -which was shown by g . l . c . (3% SE 30) to consist of methyl myristate (44%) and a mixture of methyl ketomyristates (55%) (unresolved on g . l . c ) . Chromatography, as described for methyl s tearate, provided a pure mixture of methyl ketomyristates (73;x+y=ll) (1.3 g . , 30% based on consumed s t a r t i ng mate r i a l ) . v ( C C 1 J : 1750, 1720 cm\" 1 : x (CC1„, 100 MHz) 9.10 ( t , 3H, max1 4J ' 4 • CH - ( C H J J , 8.74, 8.50 (broad s, m, 16 H, CH - ( C H 0 ) 0 ) , 7.76 (3 —j Z 6 —Z o overlapping t r i p l e t s , 6 H, - CH_ 2C0 2CH 3, -CH^-CH^-), 6.43 (s, 3 H, - C 0 2 C H 3 ) . Anal . Calcd .. .for C 1 C H 0 0 0 7 : C, 70.31; H, 10.94. i b Zo 6 Found: C, 70.21; H, 10.79. Oxidation of methyl palmitate (72,n=14) Chromium t r i o x i d e (8 g.) was ca re fu l ly added to acet ic anhydride (14 m l . ) . The r e su l t i ng so lu t ion was added dropwise over a period of one hour to a cold mixture of methyl palmitate (72,n=14) (5.6 g . , - 0.020 moles) i n g l a c i a l ace t ic ac id (24 ml.) and ace t ic anhydride (10 m l . ) . After 24 hours at room temperature, work up as described above provided a c r y s t a l l i n e s o l i d (4 g.) which was shown by g . l . c . (3% SE 30) to consist of methyl palmitate (39%) and a mixture of methyl ketopalmitates (59%) (unresolved on g . l . c ) . Chromatography, as described for methyl s tearate, provided a pure mixture of methyl keto-palmitates (73,x+y=13) (1.3 g, 31% based on consumed s t a r t ing mate r i a l ) . - 88 -v ( C C 1 J : 1750, 1725 cm\" 1 : T (CC1. , 100 MHz) 9.15 ( t , 3H, max 4 s 4 CH„-(CH 2 ) n ) , 8.76, 8.50 (broad s, m, 20H, Cti^CH^) 1 Q ) , 7.76.(3 over-lapping t r i p l e t s , 6H, -CH C02CH , - C H 2 - C - C H 2 - ) , 6.44 (s, 3H, -C0 2CH_ 3). Ana l . Calcd. for C^^Oy C, 71.82; H, 11.27. Found: C, 71.78; H, 11.46. Oxidation of methyl docosanoate (72;n=20) Chromium t r i o x i d e (8 g.) was ca re fu l ly added to ace t i c anhydride (14 ml.) and the r e s u l t i n g so lu t ion was added dropwise over a period of one hour to a cold mixture of methyl docosanoate (72, n=20) (5 g . , 0.014 moles) i n g l a c i a l ace t ic acid (24 ml.) and ace t ic anhydride (10 m l . ) . Af ter 24 hours at room temperature, work up as described above provided a c r y s t a l l i n e s o l i d (4.8 g.) which was shown by g . l . c . (3% SE 30) to consist o f methyl docosanoate (55%) and a mixture of methyl ketodocosanoates (45%) (unresolved on g . l . c ) . Chromatography, as described for methyl ketostearate, provided a pure mixture of methyl ketodocosanoates (73,x+y=19) (1.3 g . , 48% based on consumed s t a r t i ng mate r ia l ) . Vmax CCC14) 1750, 1715 cm\" 1 : x (CC1 4 , 100 MHz) 9.12 ( t , 3H, CH -(CH ) ) , 8.76, 8.50 (broad s, m, 32 H, C H , - ( C H _ ) . , ) , 7.77 (3 —o l n 0 overlapping t r i p l e t s , 6 H, - C H 2 C 0 2 C H 3 > -CH -C-CH - ) , 6.44 (s, 3H, -C0 2 CH 3 ) Anal . Calcd. for C 2 3 H 4 4 0 3 : C, 75.00; H, 11.95. Found: C, 75.18; H, 11.96. - 89 -Oxidation of methyl decanoate (72;n=8) Chromium t r i o x i d e (8 g.) was ca r e fu l l y added to ace t ic anhydride (14 ml) and the r e s u l t i n g so lu t ion added dropwise over a period of one hour to a co ld mixture of methyl decanoate (72,n=8) (5 g . , 0.025 moles) i n g l a c i a l acet ic acid (24 ml.) and acet ic anhydride (10 ml) . After 24 hours at room temperature, work up, as described above, provided a green o i l (4.7 g.) which was shown by g . l . c . (3% SE 30) to consis t o f methyl decanoate (50%) and a mixture o f methyl ketodecanoates (50%) (unresolved on g . l . c ) . Chromatography, as described for methyl s tearate , provided a pure mixture of methyl ketodecanoates (73,x+y=7) (2.4 g, 65% based on consumed s t a r t i ng mate r i a l ) . v m a x ( C C l 4 ) : 1750, 1725 cm\" 1 : T (CC1 4 > 100 MHz) 9.10 ( t , 3H, C H 3 - ( C H 2 ) 4 ) , 8.70, 8.45 (broad s, m, 8H, CH 3 (CH_ 2 ) 4 , 7.98 (s, 3H, C H 3 - C - ( C H 2 ) n ) , 7.74 (3 overlapping t r i p l e t s , 6H, - . ,9 \" CH 2 C0 2 CH 3 , - C H 2 - C - C H 2 - ) , 6.44 (s , 3H, - C O ^ j y . Anal . Calcd. for C 1 1 H 2 Q 0 3 : C, 66.00; H , 10.00. Found: C, 66.11; H, 9.91. - 90 -Acetals of methyl ketodecanoate (73;x+y=7), methyl ketomyristate (73;x+y=ll), methyl ketopalmitate (73;x+y=13, methyl ketodocosanoate (73;x+y=19). The oxidat ion products (100 mg) from methyl decanoate (72;n=8), methyl myristate (72;n=12), methyl palmitate (72;n=14), and methyl docosanoate (72;n=20) were converted to the acetals as described for methyl ketostearate. The I .R . and N.M.R. character-i s t i c s of these acetals were s i m i l a r to those of methyl ketostearate acetal (77;x+y=15). Thioacetals of methyl ketodecanoate (73;x+y=7), methyl ketomyristate (73;x+y=19). The oxidat ion products (100 mg.) from methyl decanoate (72;n=8), methyl myristate (72;n=12), methyl palmitate (72;n=14), and methyl docosanoate (72;n=20) were converted to the th ioace ta l s , as described for methyl ketostearate. The I .R. and N.M.R. character-i s t i c s of these thioaceta ls were s i m i l a r to those of methyl ketostearate th ioaceta l (78;x+y=15). - 91 -Methyl 9- and 10-ketostearate (83a,b) A so lu t ion of diborane i n tetrahydrofuran (IM; 15 ml.) was added to a so lu t ion of methyl oleate (81) (2.96 g . , 0.01 moles) i n tetrahydrofuran (100 ml) at 0°C and the reac t ion mixture subsequently s t i r r e d for 24 hours at room temperature. Aqueous sodium hydroxide (IM; 20 ml.) and hydrogen peroxide (30%; 5 ml.) were added and after 24 hours at room temperature tetrahydrofuran was removed under reduced pressure. Ext rac t ion with ether (3 x 100 ml.) and work up i n the usual way provided methyl 9- and 10-hydroxystearate (82a,b) (3.4 g.) which, without further p u r i f i -cat ion was dissolved i n acetone (100 m l . ) . Jones' reagent (CrC^-M ? S0 4 -H 7 C) v;as added dropwise u n t i l oxidat ion was complete. Removal of acetone under reduced pressure and work up . in the usual way provided a mixture of methyl 9- and 10-ketostearate. (83a,b). Vmax ^ C C 1 4 ^ 1 7 5 0 , 1 7 2 0 c m _ 1 T ( C C 1 4 » 1 0 0 MHz). 9.12 ( t , 3H, C H 3 - ( C H 2 ) n ) , 8.74, 8.48 (broad s, m, 24H, C H 3 - (CH_2) u ) , 7.74 (3 overlapping t r i p l e t s , 6H, - CH 2 C0 2 CH 3 , - CH2C0CH_2~), 6.41 (s, 3H, - C 0 2 C H 3 ) . Methyl 9- and 10-ketostearate acetal Ethyl orthoformate (2 m l . ) , ethylene g l y c o l (1 ml.) and p-toluenesulfonic acid (5 mg.) were added to a mixture of methyl 9- and 10 ketostearate (83a,b) (100 mg.). After 1 hour at 90° , - 92 -the so lu t ion was heated at 150° for 2 hours while excess e thyl orthoformate d i s t i l l e d of f . After coo l ing , saturated sodium b i -carbonate so lu t ion was added and the so lu t ion extracted with ether (3x). The combined extracts were washed with saturated sodium chlor ide so lu t ion . After drying (anhydrous sodium su l f a t e ) , removal of solvent provided a quant i ta t ive y i e l d o f aceta ls . vmax ( C C V 1 7 4 5 ' 1 1 5 0 c m _ 1 ' T ( C C 1 4 » 1 0 0 m Z j ( - t ' 3 H * C H 3 - ( C H 2 ) n ) , 8.76, 8.48 (broad s, m, 28 H, CH (CH_2) 4 ) , 7.77 • ( t , 2H, J=7 Hz, - CH 2 C0 2 CH 3 ) , 6.40 (s , 3H, - C0 2CH ) , 6.18 (s, 4H, - OCH 2CH_ 20-).-Methyl 9- and 10-ketostearate t h ioace t a l . A mixture of methyl 9- and 10-ketostearate (83a,b) (100 mg.) and ethanedi thiol (0.25 ml.) i n g l a c i a l ace t ic acid (3.2 ml.) was warmed to 50° and boron t r i f l u o r i d e etherate (0.25 ml.) added. After 3 hours at room temperature, the so lu t ion was d i l u t e d with water -and extracted with ether (3x). The combined extracts were washed with saturated sodium bicarbonate s o l u t i o n , saturated sodium chlor ide so lu t i on . After drying (anhydrous sodium su l f a t e ) , removal of solvent provided a quant i ta t ive y i e l d of th ioace ta l s . Vmax ( C C V 1 7 4 5 c m ~ 1 ' T (CC1 4 , 100 MHz) 9.14 ( t , 3H, C H 3 - ( C H 2 ) n ) , 8.74, 8.48 (broad s, m, 28H, CH 3~ (CH_2) 1 4 ) , 7.80 ( t , 2H, -CH 2 C0 2 CH 3 ) , 6.82 (s, 4H, - SCH2CH_2S- ) , 6.43 (s, 3H, - C 0 2 C H 3 ) . - 93 -Oxidation of Methyl decanoate (72;n=8) Chromium t r i o x i d e (8 g.) was ca re fu l ly added to acet ic anhydride (14 ml.) and the r e s u l t i n g so lu t ion was added dropwise over a period of one hour to a cold mixture of methyl decanoate (72;n=8) (5 g . , 0.025 moles) i n g l a c i a l acet ic acid (24 ml.) and ace t ic anhydride (10 ml.) After 24 hours at room temperature, work up, as described above, provided a green o i l (3.7 g.) which was shown by g . l . c . (3% SE 30) to consist of methyl decanoate (51%) and a mixture of methyl ketodecanoates (49%) ( p a r t i a l l y resolved on g . l . c ) . Chromatography, as described for methyl s tearate, provided three fract ions (1.65 g. 38% based on consumed s t a r t i ng mater ia l ) . Frac t ion A (retention time 2.1 min . ; 3% SE 30, 155°) v (CC1J 1745, 1720 cm\" 1 , x (CC1„, 100 MHz) 9.14 ( t , 3H, C1L-max v 4 ^ 4 —3 (CH_) ) , 8.72, 8.45 (broad s, m, 8H, CH_(CH_).), 7.74 (m, 6H, £ n 0 — - CH 2 C0 2 CH 3 , - CH -C-CH 6.44 (s, 3H, - C O ^ j y , Fract ion A (100 mg.) was converted, i n quant i ta t ive y i e l d , as described for methyl ketostearate (cf. p .85) , to the acetal (77;x+y=7) which exhibi ted two peaks on g . l . c . (3% SE 30, 155°) (retention times, 4 and 5.5 minutes), v (CC1.) 1745, 1180 cm 1 , J max K 4J ' ' x (CC1., 100 MHz) 9.12 ( t , 3H, CH - (CHJ ) , 8.60 (m, 12H, C H , ( C H J J , 7.76 ( t , 2H, - CH 2 C0 2 CH 3 ) , 6.44 (s, 3H, - C02CH_3) , 6.18 (s, 4H, - 0CH_2CH20-). The resu l t s from the mass spectra l analysis of the acetal of f rac t ion A are shown i n f i g . (23). - 94 -Fract ion A (100 mg.) was converted, i n quant i ta t ive y i e l d , as described for methyl ketostearate (cf . p . 8 6 ) , to the th ioace ta l (78;x+y=7). (CC14) 1745 cm\" 1 , x (CC1 4 , 100 MHz) 9.12 ( t , 3H •CH -(CH ) ) , 8.40 (m, 12H, CH 3 (CH_ 2 ) 6 ) , 6.80 (s, 4H, - . SCH2CH_2S-) , 6.44 (s, 3H, - C02CH_3) . The resu l t s from the mass spectra l analysis of the th ioace ta l of f r ac t ion A are shown i n f i g s . (21), (22). Frac t ion B (retention time 2.5 min, 3% SE 30, 155°) v (CC1J 1745, 1720 cm\" 1 , x (CC1J 9.12 ( t , 3H, CH - C H J ) 8.58 max 4 4 —3 2 r\\J (m, 8H, CH -CH ) ) , 7.72 (3 overlapping t r i p l e t s , 6H, -CH CO CH , Q J z 4 Z Z o - C H 2 - C - C H 2 - ) , 6.44 (s, 3H, - C O ^ ) . Fract ion B (100 mg.) was converted i n quant i ta t ive y i e l d , to the acetal (77;x+y=7) which exhibi ted two peaks on g . l . c . (3% SE 30, 155°) (retention times. 5.5 and 6.5 minutes), v (CC1 .) 1745. v - max v . H 1170 cm\" 1 , x (CC1 4 , 100 MHz) 9.12 ( t , 3H, CH - C H ^ ) , 8.60 (m, 12H, C H 3 - ( C H 2 ) 6 ) , 7.79 ( t , 2H, J=7Hz, - CH_ 2C0 2CH 3), 6.44 (s, 3H, - C 0 2 C H 3 ) , 6.22 (s, 4H, - OCH_2CH20-). The resu l t s from the mass spect ra l analysis of the acetal of f r ac t ion B are shown i n f i g s . (24), (25), (26). Fract ion B (100 mg) was converted i n quant i ta t ive y i e l d , to the th ioace ta l (73;x+y=7) v m & x (CC14) 1745 cm\" 1 , x (CC1 4 > 100 MHz) 9.12 ( t , 3H, C H - ( C H _ ) \" ) , 8.40 (m, 12H, CH,(CH„),) , 7.79 ( t , 2H, —o z n 6 —l o J=7Hz, - CH 2 C0 2 CH 3 ) , 6.82 (s, 4H, -SCH_2CH_2S-) , 6.44 (s, 3H, - C0 2CH_ 3). The resu l t s from the mass spect ra l analysis of the th ioace ta l of f rac t ion B are shown i n f i g s . (27), (28). - 95 -Fract ion C (retention time 2,7 mins . , 3% SE 30, 155°) v (CC1J 1750, 1725 cm\" 1 , T (CC1., 100 MHz) 8.70, 8.42 max v AJ 4 ' 0 (broad s, m, 10H, C H 3 ( C H 2 ) 5 ~ ) , 7.98 (s, 3H, CH - C - C H 2 ) n ) , 7.82 3 o n ( t , 2H, J=8Hz, - CH 2 C0 2 CH 3 ) , 7.69 ( t , 2H, J=7Hz, CH 3-C-CH_ 2-) , 6.44 (s, 3H, - C0 2 CH 3 ) . Fract ion C (100 mg.) was converted, i n quant i ta t ive y i e l d , to the acetal (77;x+y=7) which exhibi ted one peak on g . l l c . (3% SE 30, 155°) (retention time, 7 minutes) v (CC1.) 1750, 1175 cm\" > j v. > J m a x ^ 4; x (CC1 4 , 100 MHz) 8.80 (s, 3H, CH_ 3-C-OCH 2CH 20-), 8.70, 8.44 (broad s, m, 12H, CH 3 (CH_ 2 ) 6 ) , 7.78 ( t , 2H, - CH_ 2C0 2CH 3), 6.44 (s, 3H, - C 0 2 C H 3 ) , 6.20 (s , 4H, - OCH2CH_20-). The resu l t s from the mass spectra l analysis of che acetal of f r ac t ion C arc chcv.T. i n f i g s . (29), (30). Frac t ion C (100 mg.) was converted, i n quant i ta t ive y i e l d to the th ioaceta l (78;x+y=7). (CC14) 1750 c m - 1 T (CC1 4 , 100 MHz) 8.66, 8.50 (broad s, m, 12H, C H , ( C F L ) J , 8.32 (s, 3H, CH_-6 —Z o —J C-SCH 2 CH 2 S-), 7.78 ( t , 2H, -CH 2 C0 2 Me), 6.78 (s, 4H,-SCH_2CH_2S-), 6.44 (s , 3H, -C0 2CH_ 3). The resu l t s from the mass spect ra l analysis of the th ioaceta l of f r ac t ion C are shown i n f i g s . (31), (32). - 96 -Dihydrocampherenone (85) Campherenone (84) (1 g . , 0.0045 moles) i n ethyl acetate (100 ml.) was treated with 10% Pd-C (150 mg.) and hydrogen for 4 hours. After f i l t r a t i o n of the so lu t i on , removal of solvent provided dihydrocampherenone (85) as a colourless o i l (940 mg. 94%). v (CC1J 1740. cm\" 1 , max 4 Dihydroisocampherenol (86) Dihydrocampherenone (85) (940 mg., 0.0042 moles) i n dry ethyl ether (150 ml.) was treated with excess l i t h ium aluminium hydride at ref lux for 24 hours. After coo l ing , e thyl acetate was added to destroy excess l i t h ium aluminium hydride and the so lu t ion chlor ide so lu t ion , and dr ied (anhydrous sodium su l f a t e ) . Removal of solvent provided dihydroisocampherenol (86) as a colourless o i l (780 mg., 84%). v (CC1.) 3500 cm\" 1 , max 4 Dihydroisocampherenyl acetate (87) Dihydroisocampherenol (86) (780 mg. 0.0035 moles) i n pyr id ine (3 ml.) and acet ic anhydride (0.5 ml.) was heated at 90° for 24 hours. After coo l ing , the so lu t ion was d i l u t ed with water and extracted with' ether (3x). The combined extracts were washed successively with d i l u t e hydrochloric ac id , saturated sodium bicarbonate so lu t ion and - 97 -saturated sodium chlor ide s o l u t i o n . After drying (anhydrous sodium su l fa t e ) , removal of solvent provided a dark coloured o i l . . Column chromatography over aluminium oxide , (neutra l Grade IV) gave, by e lu t ion with pet. ether, dihydroisocampherenyl acetate (87) (740 mg; 75%) as a colourless o i l - homogeneous by - g . l . c . analysis (3% SE 30, 170°) , [ a ] 2 2 - 31.3 (c. 3.61, CHC1 ) . v (CC1J 1745, 1240 cm\" 1 . x (CC1., 60 MHz) 9.16 (s, 6H max v 4J ' v 4 ' K ' 2 CH - ) , 9.07 (s, 3H, CH 8.10 (s, 3H, - 0 2CCH_ 3), 5.40 (dd, IH, -CHOAc). Oxidation of dihydroisocampherenyl acetate (87) Chromium t r i o x i d e (840 mg.) was added to acet ic anhydride (8 ml.) and the r e su l t i ng so lu t ion added dropwise over a period of one hour to a cold mixture of dihydroisocampherenyl acetate (87) (430 mg., 0.0016 moles) i n g l a c i a l ace t ic ac id (7.2 ml.) and acet ic anhydride (2.8 m l . ) . The so lu t ion was heated at 90° for 1 hour and, after coo l ing , saturated sodium bicarbonate so lu t ion was caut iously -added to the react ion mixture. Excess acet ic anhydride was removed under reduced pressure and the r e s u l t i n g green so lu t ion extracted with ether (4x). The combined extracts were washed successively with 5% sodium hydroxide, saturated sodium bicarbonate so lu t ion and saturated sodium chlor ide so lu t ion . After drying (anhydrous sodium su l f a t e ) , removal of solvent gave a yellow o i l (187 mg.) which was shown by g . l . c . analysis (3% SE 30, 170°) to consist of dihydroisocampherenyl acetate (87) (10%) and one product (90%) (retention time 7.1 minutes). - 98 -Column chromatography of 120 mg, of the mixture over aluminium oxide (neutral Grade IV) gave, by e lu t ion wi th pentane, 5-ketodihydroisocampherenyl acetate (88) (70 mg., 24%). v (CC1J 1745, 1730, 1240 cm\" 1 , x (CC1., 100 Hz) max A 4 9.18 (s, 3H, CH - ) , 9.16 (s, 3H, CH - ) , 8.06 (s, 3H, -0 CCH ) , • 0 / 6 7.67 (m, 3M, - CH^-C-, bridgehead H) , 5.36 (dd, IH, -CHOAc); m/e 280 (M + ) . 5-Ketodihydroisocampherenol (89) 5-ketodihydroisocampherenyl acetate (88) (48 mg., 0.0002 moles) was treated with a so lu t ion of sodium carbonate (25 mg.) i n water (1 ml) and methanol (0.6 ml.) for 24 hours at 40-50° . A i t e r coo l ing , the react ion mixture naz extracted \",'ith ether (4x) and the combined extracts dr ied (anhydrous sodium su l f a t e ) . Removal of solvent provided 42 mg. of a yellow o i l , homogeneous by g . l . c . analysis (3% SE 30, 170°, re tent ion time 11.3 minutes). v (CC1J 3450, 1725, 1410 cm\" 1 , x (CC1., 60 MHz) 9.17 max 4 . 4 . ; ; ; (s, 3H, C H 3 - ) , 9.10 (s, 3H, CH^-) , 6.42 (dd,\" IH, - CHOH)-.\"'\"' 5-ketodihydro-g- santalene (90) Methane su l fonyl chlor ide (90 mg.) was added to a so lu t ion of 5-ketodihydroisocampherenol (89) (42 mg. 0.00018 moles) i n pyr id ine (1 ml . ) ' and the react ion mixture was heated at 100°, - 9 9 -under ni t rogen, for 48 hours. After coo l ing , the so lu t ion was d i lu ted with water and extracted with ether (4x). The combined extracts were washed with d i l u t e hydrochloric acid and saturated sodium chlor ide so l tu ion and dried (anhydrous sodium su l fa te ) , Removal of solvent and column chromatography over aluminium oxide (neutral Grade I) gave, by e lu t ion with pet . ether/ether (90:10), 24 mg. (64%) 5-ketodihydro-B-santalene (90): homogeneous by g . l . c . analysis (3% SE 30, 170°; re tent ion time 3.8 minutes). v (CC1J 1735, 1660, 880 cm\"1.\" x (CC1., 100 MHz) 8.94 max -4 4 0 n (s, 3H, C H 3 - ) , 7.68 ( t , 2H, -CH^C- ) , 7.32 (broad s, IH, • a l l y l i c bridgehead H) , 5.43 (d, 2H, J=13 Hz; CH_2=); m/e 220 (M + ) . - 100 -BIBLIOGRAPHY• A. W, Hofmann, Ber . , 16, 558 (1883); K. Lbf f l e r and C, Freytag, i b i d , 42, 3427 (1909). E. J . Corey and W.R. Her t l e r , J . Am. Chem. Soc. , 80, 2913 (1958) and 81_, 5209 (1959); P. Buchschacher, J . Kalvoda, D. Ar igon i and 0. Jeger, i b i d , 80, 2905 (1958). D.H.R. Barton, J . M . Beaton, L . E. Ge l l e r and M. M. 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