Total synthesis of steroids. Part 2. Preparation of C-10 methylated steroids. Regio- and stereocontrol in a diene addition to methyl Z-2-methyl-4-oxo-2-pentenoate

Abstract

A twelve-step total synthesis of 14-epi-androsta-4,9(11),15-triene-3,17-dione from methyl vinyl ketone, 2-methylcyclo-hexane-1,3-dione, acetylene, and methyl Z-2-methyl-4-oxo-2-pentenoate is described. Crucial steps include a stereo- and regio-selective diene addition, an efficient formation of ring D by C-acylation of an acetyl group, and a selective bromine substitution at C-15 in a 15,17-dione intermediate. The stereo- and regioselectivity of the diene addition is generalized for certain other bifunctional aliphatic dienophiles.