A synthetic approach to C-nor-D-homosteroids based on a cascade of radical cyclisations from a vinylcyclopropane-substituted acyl radical precursor

Abstract

Treatment of the arylvinylcyclopropane-substituted seleno ester 5 with Bu 3SnH–AIBN, under high dilution in benzene at 80 °C, led to a 1:1 mixture of C10 methyl epimers of the C-nor-D-homosteroid ring system 24/ 25. The homosteroid was formed from 5 via a cascade of sequential acyl 13- endo trig radical macrocyclisation, benzyl radical 5- exo trig transannulation and alkyl radical transannulation reactions ( Scheme 1). The macrocyclic dienone 23 was also isolated as an intermediate in the radical cascade between 5 and 24/ 25, and the dioxolanes 29 were interesting by-products. The cascade of radical cyclisations leading to the homosteroid 24/ 25 from the acyl radical precursor 5 is compared and contrasted with similar radical cascades from arylvinylcyclopropane-substituted alkyl radical precursors, i.e, 30→ 31 and 32b→ 38.