α-Methoxythioanisole. Further Uses as an Umpolung Reagent

Abstract

The facile lithiation of thioacetals has led to their extensive development as Umpolung reagents of great utility in general organic synthesis.¹ In contrast, the corresponding monothioacetals, such as α-alkoxysulfides, have received little attention for similar synthetic purposes. The most investigated reagent of this class has been the α-lithio derivative (2) of α-methoxy-thioanisole (methoxymethylphenylthioether, 1), which we will henceforth refer to as LMT. The first reported use of LMT was in 1975 by Trost, who showed that it added cleanly to the carbonyl of several bicyclic lactones.² Subsequent studies of LMT have been limited to one example of its addition to a lithiated tosylhydrazone to give eventually an enol ether,³ and several cases of its addition to ketone carbonyls as the first step of an unsaturated aldehyde synthesis.^4,5 We now report a new, convenient and non-hazardous synthesis of α-methoxythioanisole (1), as well as a broad overview of the reactions of its lithio derivative LMT (2) with some representative alkyl halides, epoxides, aldehydes, nitriles, amides, and an ester and an acid chloride.