Highly Stereocontrolled Formal Synthesis of Brassinolide via Chiral Sulfoxide-Directed SN2‘ Reactions

An efficient stereocontrolled methodology for the preparation of the four contiguous chiral centers of the brassinosteroid side chain is described. Allylic mesyloxy sulfinyl steroids have been found to undergo highly stereoselective S N 2‘ displacements when treated with cyanocuprates that provide the required acyclic stereocontrol in the key C-24 position of the steroidal side chain. Preparation of a direct precursor of brassinolide 1, as well as a precursor of naturally occurring (24 R )-epibrassinolide, (+)-18, is carried out in two additional steps utilizing asymmetric dihydroxylations of (22 E )-olefins (+)-2 and (+)-17 . In this manner, a formal synthesis of this plant growth promoter has been completed, and the extension of the scope of this methodology has been explored providing a straightforward route to this family of steroids. Alternative routes to the key olefin (+)-2 are also outlined. Improved selectivity in the addition to aldehyde 7 for the preparation of the Cram (22 R )-allylic hydroxy sulfoxides is achieved by controlling the chirality at sulfur or by a condensation−symmetric oxidation sequence employing the analogous vinyl sulfide reagent 22 .