Methylation of steroidal C(3)-ketones: A conformational analysis.

Abstract

The synthesis of 5beta-cholest-7-en-3-one (47) is described. Methylation of this compound results in 2beta-methyl-5beta-cholest-7-en-3-one (62) and 2,2-dimethyl-5beta-cholest-7-en-3-one (63). The structure of (62) was proven by its conversion to the known 2beta-methyl-5beta-cholestan-3-one (66). An explanation is offered for the uncharacteristic mass spectrum exhibited by the ethylene ketal of (62). The structure of (63) was proven primarily from the mass spectrum of its ethylene ketal. The optical rotatory dispersion curves of the above compounds are reported and discussed. The fact that methylation of (47) occurs at C2 rather than C4 is explained by invoking conformational transmission effects in the enolate anion formation step in the reaction. Use is made of Bucourt's rules of dihedral angle changes in describing the conformational transmission effects. Enol acetylation of (47) results in a large predominance of the C2, C3 unsaturated enol acetate.