14-Methyl steroids. Part 5. Structural features influencing stereoselectivity of 14-methylation of 15-oxo-19-norsteroids: synthesis of 14α-methyl-19-norprogesterone

Abstract

Methylation of 3-methoxy-14β-estra-1,3,5(10),8-tetraen-15-one (5) in the presence of base affords a ca. 5 : 1 mixture of the corresponding 14α- and 14β-methyl compounds (6) and (7) respectively, whereas similar treatment of 20,20-ethylenedioxy-3-methoxy-19-norpregna-1,3,5(10)-trien-15-one (15) results in exclusive formation of the 14α-methyl product (18). The latter compound (18) has been converted into 14α-methyl-19-norprogesterone (23). The stereoselectivity of 14-methylation of 15-ketones is correlated with the propensity of ring D to adopt a quasi-trans or quasi-cis conformation in the derived enolate, leading to preferred 14α-or 14β-methylation respectively.