New strategies for diversifying steroidal scaffold to generate b17-heterocycle-substituted derivatives from a common readily accessible intermediate

This article presents new strategies for diversifying a steroidal skeleton to access various b17-oxygen heterocycle-substituted scaffolds. Using pregnenolone as the starting building block, a common propargyl alcohol-containing intermediate 1 was accessed in 4 steps, 60% overall yield. This intermediate (1) was subsequently explored in cyclative transformations with the objective to generate various 5- or 6-membered oxygen-containing heterocycles at the C17-position of pregnenolone. As the result of these studies, four different subsets of catalytic conditions were identified to achieve divergent single-step function-alizations of 1 to access furane-substituted scaffold 2 (51% yield), butenolide-containing scaffold 3 (28% yield), and 6-membered lactones 4 (23% yield) and 5 (22% yield). In addition, single-step conversion of 1 into allene-containing product 17 was accomplished by exposing 1 to catalytic phosphines in 34-38% yield.