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

17 thoxy-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 sel ectivity, higher alkyllithium species (n-BuLi, t-BuLi) preferred to ad d to the beta-face of 4. 7 alpha-Substituted derivatives, on the other hand, were generated stereoselectively by utilizing alkynyllithium re agents in the addition step. Removal of the phenylsulfonyl group at C( 6) from alkylated products was achieved by conventional reductive desu lfonylation methods. A short synthesis of the estrogen receptor antago nist 1 exploiting these observations is presented.