CONTROLLED ALKALINE HYDROLYSIS OF STEROIDAL α-BROMOKETONES: NEW CONDITIONS AND SYNTHESIS OF 2α-HYDROXY-3-ONES

Article abstract of DOI:10.1016/0039-128X(82)90152-0

Controlled alkaline hydrolysis of 16α-bromo-17-keto steroids 1, 5 and 7 with potassium carbonate and tetra-n-butylammonium hydroxide (n-Bu4NOH) 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.Treatment of the bromoketones 1, 5 and 7 with potassium carbonate in aqueous acetone or with n-Bu4NOH in aqueous dimethylformamide (DMF) gave 16α-hydroxy-17-ones 3, 6 and 8 in 85-90percent 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.