Stereoelectronically Controlled, Thallium(III)-Mediated C-19 Degradation of 19-Hydroxy Steroids. An Expedient Route to Estrone and its Congeners via 19-Nor-10β-hydroxy Intermediates

Article abstract of DOI:10.1021/jo00097a056

Estrone (8b) has been synthesized in four steps from 3β-acetoxy-19-hydroxyandrost-5-en-17-one (2b), readily available from an industrial precursor.A key feature of the strategy is a stereoelectronically controlled, Tl(III)-mediated degradation (2b -> 5b).Oppenauer oxidation of diol 6b, resulting from saponification of the acetate 5b, afforded the unsaturated 10β-hydroxy ketone 7b, acid treatment of which induced aromatization affording 8b.An alternative route including dehydration (5b -> 9b) followed by Oppenauer oxidation (10b -> 8b) gave comparable results.This strategy has first been developed with the aid of cholestane model compounds (2a -> 5a) and then successfully applied to the synthesis of analogues in the cholestane, androstane, and pregnane series to produce the corresponding 19-nor-10β-hydroxy derivatives 7a-d and A-aromatic steroids 8a-d.