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

• Published in: Journal of organic chemistry 2016-05, Vol.81 (10), p.4252-4261
• Main Authors: Raghavan, Sadagopan, Chiluveru, Ravi Kumar, Ganapathy Subramanian, S
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b00616

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.