Synthetic application of lithiated tris(methylthio)methane: preparation of aliphatic methyl thiolcarboxylates from the corresponding halides. Convenient synthesis of tris(methylthio)methane

Abstract

A thorough study directed towards the synthesis of methyl thiolcarboxylates was made on the basis of the following steps: (i) conversion of alkyl halides into the corresponding trimethyl trithioorthocarboxylates by using tris(methylthio)methyllithium in THF at –78 °C; (ii) selective hydrolysis of the intermediates to methyl thiolcarboxylates by using 35% aq. HBF₄ in DMSO or, in some cases, in THF. The overall yields of the two stages are, usually, between 70 and 88%. By this procedure it is also possible to incorporate ⁸O in the carbonyl group of thiol esters (∼98% isotopic purity). Furthermore, a new, convenient method for the preparation of tris(methylthio)methane as the precursor of tris(methylthio)methyllithium was developed.