6,19-Carbon-bridged steroids. Synthesis of 6,19-methanoprogesterone

Abstract

6,19-Methanoprogesterone (4) was synthesized in nine steps from the readily available 3β,20β-diacetyloxy-5α-bromo-6,19-oxidopregnane (5) in 14% overall yield. The additional carbon atom was introduced by reaction of a C-19 aldehyde with Ph₃PCHOCH₃ under salt free conditions and subsequent hydrolysis to give the homologous aldehyde. Intramolecular addition of the newly incorporated carbonyl (C-19a) to the olefinic C-6 in ring B was achieved by means of a Prins reaction with TiCl₄ as Lewis acid.