Catalyst-Free Synthesis of Phosphorothioates via P–S Coupling ­Reaction of Dialkyl Phosphites with Thiols

Abstract

A catalyst-free synthesis of phosphorothioates via a P-S cross coupling reaction of thiols with dialkyl phosphites has been studied. By presented method, various phosphoroatioates are obtained by the reaction of thiols with H-dialkyl phosphites in the presence of DMSO as a solvent and oxidant under transition metal-free conditions. Mechanistic studies showed that the reaction is proceeded with formation of a known disulfide intermediate via the oxidation of thiols in the presence of DMSO. Nucleophilic substitution of dialkylphosphite with the disulfide intermediate gave phos-phorothioate. The presented method is a convenient process for the synthesis of phosphorothioates under catalyst-free condition.