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. With presented method, various phosphorothioates were obtained by the reaction of thiols with H-dialkyl phosphites in the presence of DMSO as both solvent and oxidant under transition-metal-free conditions. Mechanistic studies showed that the reaction proceeds with formation of a known disulfide intermediate via the oxidation of thiols in the presence of DMSO. Nucleophilic substitution of dialkyl phosphite with the disulfide intermediate gave phosphorothioate. The presented method is a convenient process for the synthesis of phosphorothioates under catalyst-free conditions.