Stereoselective Formal Synthesis of (+)- and (-)-Cyclophellitol and (-)-Conduritol-B and Synthesis of (-)-Conduramine-B Derivative Using a Sulfinyl Moiety for C-O Bond Formation and α-Chloro Sulfide for C-C Bond Formation.

Abstract

The formal total synthesis of both the enantiomers of cyclophellitol and conduritol-B and synthesis of conduramine-B derivative have been achieved from a common intermediate, obtained by regio- and stereoselective vicinal functionalization of a diene utilizing an intramolecular sulfinyl group as a nucleophile, followed by stereoselective preparation of an allylic sulfide by reaction of vinylzinc bromide with an electrophilic α-chloro sulfide, and last by ring-closing metathesis reaction as the key steps. The sulfoxide, sulfilimine, and sulfur ylid prepared from this common intermediate have been transformed into derivatives of conduritol-B, conduramine-B, and (-)-cyclophellitol, respectively. The silyl sulfide was converted via sila-Pummerer rearrangement, hydrolysis, and reduction in an one-pot operation to a hydroxymethyl group. [2,3]-Wittig-Still rearrangement was employed for the synthesis of (+)-cyclophellitol. The potential utility of sulfur intermediates as nucleophilic and electrophilic partners in total synthesis is elegantly demonstrated.