Photooxygenation of 1,3-Cholestadiene and Related Compounds

Abstract

In an effort to effect stereoselective and regioselective total syntheses of the sesquiterpenes intermedeol(1) and tauresmisin ( 5 ) , homoannular dienes (2) (5-epi-lO-epieudesma-1,3,11-triene) and 4 (6, 11/3H-eudesrna-1,3-dien-6,13-olide) were subjected to photochemical oxygenation. Diene 2 gave a complex mixture of products, while 4 gave mixtures of santonin and hyposantonin, the result of a photochemical ene reaction. The expected endoperoxides could not be detected. 1,3-Cholestadiene (18) was also subjected to photochemical oxygenation and gave l,.l-cholestadien-3-one (19) as the only isolable product derived from 18. These results are discussed in terms of the steric requirements for endoperoxide formation. The syntheses of compounds 2 and 4 are described, and methods of preparation of 1,3-cholestadiene are discussed.In the course of a general synthetic program in the sesquiterpene field, a variet of approaches to the 10-epieudesmane group of these natural products have been explored.2 A major goal of this program was a convenient total synthesis of intermedeol3 (5-epi-10-epieudesma-Il-en-4~-01, I), a presumed biosynthetic precursor of the valencene-nookatone group of sesquiterpenes. An attractive regioselective and stereoselective synthetic approach to 1 involved the photooxygenation of 5-epi-lO-epieudesma-1,3,11-triene (2), to give endoperoxide 3 which could be converted to intermedeol in a relatively few steps. In addition, the photooxygenation product of the related diene (4) derived from santonin4 could serve as a precursor for another sesquiterpene, tauremisin (5).5 SchemeI 0 rnfBQ?f 6 1 7 9 1 2 0 3 4 5 Il, R = OH 12, R = C1 l 3 , R , R = O 14 15, R = H R = OOH 16 17 18 19Triene 2 was prepared from 4-epi-5-epi-10-epieudesm-11-en-3-one (6)6 as outlined in Scheme I. Utilizing a modification of a procedure employed in a total synthesis of occidental01,~ ketone 6 was condensed with ethyl formate and the resulting formyl compound brominated to give a-bromo ketone 7, which was smoothly dehydrohalogenated to enone 8. Reduction of 8 with potassium tri-sec-butylborohydrides quite unexpectedly gave 4-epi-5-epi-lO-epieudesm-ll-en-8