Synthesis of hydroxylated steroid hormones via conjugate addition of a silyl-cuprate reagent

Article abstract of DOI:10.1016/0039-128X(94)90102-3

The synthesis of several hydroxylated steroids via conjugate addition of Fleming's silyl-cuprate reagent, (PhMe2Si)2CuLi, a masked hydroxyl group, to the appropriate enone was studied.By this means 7α-hydroxytestosterone (7) was obtained in good yield from 17β-hydroxyandrosta-4,6-dien-3-one (1a), though similar reactions on 17β-hydroxyandrosta-1,4-dien-3-one (8) gave a low yield of 1α-hydroxytestosterone (13) chiefly through the poor conversion of the phenylsilyl intermediate into the halogenosilane. 3β,16α-Dihydroxy-5α-pregnan-20-one (18b) was obtained in a similar manner from 3β-hydroxy- 5α-pregn-16-en-20-one and 5α-cholestane-1α,3α-diol (17) was produced from the 1-en-3-one (14) via conjugate addition of the silyl group, reduction of the carbonyl function, and oxidative removal of the silyl group. - Keywords: hydroxylated steroids; 7α-hydroxytestosterone; 1α-hydroxytestosterone; 3β,16α-dihydroxy-5α-pregnan-20-one; 5α-cholestane-1α,3α-diol