Stereoselective synthesis of 24-alkyl-22-hydroxysterols based on chelation-controlled radical reactions

Abstract

We have shown that the diastereoselectivity in the radical-mediated reactions of steroidal 24-methylene-22-oxy-25-oic acid esters 6–11 with alkyl iodides performed in the presence of Lewis acid MgBr₂·OEt₂ depends on the bulk of the alkyl iodides, the oxy groups at C-22 and the configuration at C-22. The ethylation of 9 afforded the syn-adduct exclusively and the methylation of 6 and 7, ethylation of 10 and isopropylation of 9 gave syn-adducts with high selectivities (syn–anti = 8.8–5.1∶1). Other combinations, except for the tert-butyl radical addition to 6, 7 and 10 predominantly yielding anti-adducts, showed lower syn-selectivities.