Total synthesis of steroids. Part 1. Ring A aromatic compounds. Regiocontrol in diene additions with 6-methoxy-1-vinyl-3,4-dihydronaphthalene

Abstract

A total synthesis of ring A aromatic D-homosteroids and the conversion of one of them to estrone and its derivatives are described. The key reaction is a catalysed addition of 6-methoxy-1-vinyl-3,4-dihydronaphthalene to 2,6-dimethyl-1,4-quinone which proceeds with orientation inversion compared to the thermal addition. Reactions with several other quinones are described. The synthetic sequence includes a hydride reduction in which an apparently more hindered carbonyl group of an enedione system is reduced preferentially. Cyclization of a 1,6-keto aldehyde under acidic conditions gives the desired acetyl cyclopentene derivative, while a predominant formation of cycloheptenones is observed when the same cyclization is performed with base.