Hydroxylation of Δ4-steroids by osmium tetraoxide; stereochemistry and substituent effects

Abstract

Hydroxylation of cholest-4-ene by osmium tetraoxide leads preferentially to the 4β,5β-diol; this preference is even more pronounced in the case of 3α-acetoxycholest-4-ene. By contrast, α-attack is favoured in the case of 3β-acetoxycholest-4-ene. Similar results have been obtained in an analogous 19-nor series, but with a slightly greater proportion of β-attack in all comparable cases. It is suggested that the ring A conformation of the reactant or a derived complex is the primary factor determining the stereoselectivity of the reaction. The major role of a proximate substituent is to anchor the appropriate conformation favouring α- or β-attack. This argument is supported by the results of hydroxylation of 2α- and 2β-acetoxycholest-4-ene.