Convergent Synthesis of Vitamin D3 Metabolites. Control of the Stereoselectivity in Samarium-Induced Cyclopropanations of Cyclopentenes

The 25-hydroxy and 1α,25-dihydroxy vitamin D3 metabolites are obtained by solvolytic rearrangements of the 1-desoxy and 1α-hydroxy cyclopropyl vinylogous alcohols 31 and 29, respectively, with simultaneous formation of the vitamin D structural triene and the 3-hydroxy function. Two complementary methods have been employed to direct the stereoselectivity of the samarium induced olefin cyclopropanations which ultimately lead to key chiral ring A precursors. One protocol uses the two stereogenic centers of the (R,R)-2,3-butanediol ketal moiety of 8, while the other method uses the allylic hydroxyl group of (R)-16.