Stereochemistry of reduction of pregnan-20-ones with alkali metals

Abstract

The reduction of 5α-pregnan-20-one gives the 20α- and 20β-ols, with wide variations in the relative yields according to the reagent used. Alkali metals dissolving in alcohols generally give an excess of the less stable 20α-ol, although the product ratio depends upon the metal, and also upon the solvent alcohol. 5α,17α-Pregnan-20-ols often appear as by-products; the (17α)20β-ol usually predominates, but again the relative yields of isomers depend upon reaction conditions. These and other related observations are rationalised by conformational analyses of the reacting systems. A mechanistic scheme is proposed in which product ratios are decided by a delicate balance between competing routes for protonolysis of transient C-metal bonds.