Bridged-ring steroids. II. The synthesis of bridged steroids with a bicyclo[2.2.1]heptane ring A system

Abstract

Bridged steroids with a bicyclo[2.2.1]heptane ring A system are formed on thermolysis of 5-vinyl 3-keto steroids. 5-Vinyl-5α-cholestan-3-one (26) on being heated at 350 °C in decalin gave 2α,5-(syn-methylmethano)-5α-cholestan-3-one (27). Similar treatment of 17β-hydroxy-5-vinyl-5β-estran-3-one (21) gave 17β-hydroxy-2β,5-(syn-methylmethano)-5β -estran-3-one (30), which was also obtained by reduction of 2β,5-(syn-methylmethano)-5β-estrane-3,17-dione (31) with sodium borohydride on alumina. Compound 31 was formed as the major product on thermolysis of 5-vinyl-5β-estrane-3,17-dione (24) at 350 °C, together with 5-(trans-propenyl)-A-nor-5β-estrane-3,17-dione (32). Compounds 27, 30, and 31 are considered to arise via intramolecular ene reactions of the Δ2-enols of compounds 26, 21, and 24, respectively. Compound 32 is postulated to be formed via an analogous reaction of the Δ3-enol of 24, followed by thermolysis of the resulting 3′-methyl-4β,5-dihydrocyclopropa[4,5]-5β-estrane-3,17-dione (36). Photolysis of 30 in methanol results in α-cleavage of the C2—C3 bond and the formation of a ketene-derived ester and two enal-derived oxetanes.