Stereoselective hydrolysis of 16α-halo-17-keto steroids and long-range substitution effects on the hydrolysis of 16α-bromo-17-ketones and 2α-bromo-3-ketones

Article abstract of DOI:10.1016/0039-128X(85)90005-4

Epimerization of 16α-chloro- (1a), bromo- (1b), and iodo-3β-hydroxy-5-androsten-17-one (1c) by a brief treatment with 0.2 equiv NaOH in aqueous pyridine reached equilibrium between 16α- and 16β-halo ketones. 16α-/16β-Halo ketone ratios at equilibrium were 1.5 for Cl, 1.25 for Br, and 1.0 for I. Kinetic analysis showed that compounds 1a-c were stereoselectively converted to the corresponding 16α-hydroxy derivative 3 by an S(N)2 mechanism, in which the order of the apparent reactivity was Br > I > Cl. The hydrolysis of a number of 16α-bromo-17-ketones and 2α-bromo-3-ketones was carried out. The yields of the corresponding alcohols were found to depend on remote structural features in the steroids.