STEREOELECTRONICALLY CONTROLLED, THALLIUM(III)-MEDIATED C-19 DEGRADATION OF 18-HYDROXY STEROIDS - AN EXPEDIENT ROUTE TO ESTRONE AND ITS CONGENERS VIA 19-NOR-10-BETA-HYDROXY INTERMEDIATES

Estrone- (8b) has been synthesized in four steps from 3 beta-acetoxy-1 9-hydroxyandrost-5-en-17-one (2b), readily available from an industria l precursor. A key feature of the strategy is a stereoelectronically c ontrolled, TI(III)-mediated degradation (2b --> 5b). Oppenauer oxidati on of diol 6b, resulting from saponification of the acetate 5b, afford ed the unsaturated 10 beta-hydroxy ketone 7b, acid treatment of which induced aromatization affording 8b. An alternative route including deh ydration (5b --> 9b) followed by Oppenauer oxidation (10b --> 8b) gave comparable results. This strategy has first been developed with the a id of cholestane model compounds (2a --> 5a) and then successfully app lied to the synthesis of analogues in the cholestane, androstane, and pregnane series to produce the corresponding 19-nor-10 beta-hydroxy de rivatives 7a-d and A-aromatic steroids 8a-d.