Controlled alkaline hydrolysis of steroidal α-bromoketones: New conditions and synthesis of 2α-hydroxy-3-ones

Abstract

Controlled alkaline hydrolysis of 16α-bromo-17-keto steroids 1 , 5 and 7 with potassium carbonate and tetra-n-butylammonium hydroxide (n-Bu 4NOH) and synthesis of 2α-hydroxy-3-ones 11 , 13 and 16 by the controlled hydrolysis of the corresponding 2α-bromo-3-ones 9 , 12 and 15 are described. Treatm carbonate in aqueous acetone or with n-Bu 4NOH in aqueous dimethylformamide (DMF) gave 16α-hydroxy-17-ones 3 , 6 and 8 in 85–90% yield, respectively. 2α-Hydroxy-3-ones 11 , 13 and 16 were obtained by hydrolysis of the corresponding bromoketones 9 , 12 and 15 in high yields using the above conditions or sodium hydroxide in pyridine or DMF, respectively. Deuterium labeling experiments suggested that equilibration between the 2α-bromoketone 9 and the 2β-bromo isomer 10 precedes the formation of the ketol 11 in which the true intermediate might be the 2β-isomer 10 . However, rearranged androstane derivatives, 3β-hydroxy-2-ones 18 and 20 , were stereoselectively obtained by treatment of the bromoketones 12 and 15 with an excess amount of sodium hydroxide.