A NEW, STEREOSELECTIVE APPROACH TO C(7)-ALKYLATED ESTRA-1,3,5(10)-TRIENE DERIVATIVES

17 beta-Acetyloxy-3-methoxy-6-(phenylsulfonyl)estra-1,3,5(10),6-tetraene (4) was prepared as a substrate for conjugate addition of organolithium reagents by a three-step sequence starting from 17 beta-acetyloxy-3-methoxyestra- 1,3,5(10)-trien-6-one (2). While methyllithium showed only poor face selectivity, higher alkyllithium species (n-BuLi, t-BuLi) preferred to add to the beta-face of 4. 7 alpha-Substituted derivatives, on the other hand, were generated stereoselectively by utilizing alkynyllithium reagents in the addition step. Removal of the phenylsulfonyl group at C(6) from alkylated products was achieved by conventional reductive desulfonylation methods. A short synthesis of the estrogen receptor antagonist 1 exploiting these observations is presented.