The α-alkoxycarbonylation of saturated carbonyl compounds. The synthesis of 17α-hydroxymethyl 20-keto steroids

Abstract

It is shown that enolate ions, in particular lithium enolates obtained from enol acetates of saturated ketones by reaction with methyllithium, may not only be alkylated and carboxylated, but also alkoxycarbonylated (in position a to the original saturated keto group). By this method, saturated 20-keto steroids were transformed into 17α-methoxycarbonyl 20-ketones. Thus, from pregnenolone, 17-methoxycarbonylpregnenolone was prepared and was then converted to 17-hydroxymethylprogesterone and to some of its esters. This method for preparing 17-hydroxymethylated hormone analogues of the progesterone-corticoid group is simpler and more efficient than the pathway implying a free-radical functionalization of a 17α-methyl group.