The 16α-alkylation was achieved via treatment of 3-methoxyestra-1,3,5(10)-trien-17-one-N,N-dimethylhydrazone (118) with n-butyllithium and the appropriate haloalkane to afford exclusive 16α-substitution (119). Subsequent, cupric ion-catalysed hydrolysis, 17-ketone reduction and removal of the 3-hydroxyl protecting group, furnished 16α-methylestra-1,3,5(10)-trien-3,17β-diol (122a) and 16α-ethylestra-1,3,5(10)-trien-3,17β-diol (122b). An alternative sequence to the 16α-ligands, by direct alkylation of the 17-keto-estrone enolate, was also investigated. In this manner 16α-allylestra-1,3,5(10)-trien-3,17β-diol (122c) and 16α-benzylestra-1,3,5,(10)-trien-3,17β-diol (122d) were obtained.