Stereoelectronically Controlled, Thallium(III)-Mediated C-19 Degradation of 19-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 3β-acetoxy-19-hy- droxyandrost-5-en-17-one (2b), readily available from an industrial precursor. A key feature of the strategy is a streoelectronically con- trolled, 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 aro- matization affording 8b. An alternative route including dehydration (5b → 9b) followed by Oppenauer oxidation (10b → 8b) gave comparable resul- ts. This strategy has first been developed with the aid of cholestane model compounds (2a → 5a) and then successfully applied to the synthe- sis of analogues in the cholestane, androstane, and pregnane series to produce the corresponding 19-nor-10β-hydroxy derivatives 7a-d and A-aro- matic steroids 8a-d