Stereoselective synthesis of trans-THF rings using an oxidative cyclisation-radical deoxygenation sequence: application to the formal synthesis of trans-(2R,5R)-linalool oxide

Abstract

An efficient stereoselective synthesis of cis-2,5-disubtituted tetrahydrofuran (THF) diols has been achieved using permanganate-mediated oxidative cyclisation of 1,5-diene precursors. The facial selectivity during the course of cyclisation was induced by incorporating conveniently accessible chiral auxiliaries such as (2R)-10,2-camphorsultam, (S)-4-benzyloxazolidin-2-one and (−)-8-phenylmenthol. The use of (2R)-10,2-camphorsultam furnished the desired THF product as a single isolated diastereoisomer. Conformational analyses are presented to rationalize the origin of facial selectivity and synthetic investigation towards successfully accomplished transformation of cis-2,5-disubstituted THF diols into corresponding trans-THF compounds is also described, leading to a stereoselective formal synthesis of trans-(2R,5R)-linalool oxide.