Thioamide construction via sulfur interrupted Brook rearrangement

Thioamide was straightforwardly constructed via a chemoselective one-pot synthesis, employing acylsilanes in conjunction with diverse amines and elemental sulfur. The driving force of thioamidation stemmed from silane migration, a synergy process of lone pair electron attack from amine and more stable Si-O bond formation, followed by the nucleophilic activation of elemental sulfur via carbanion intermediate. The leaving trend of trimethylsilanolate and nucleophilicity of linear polysulfur facilitated the cleavage of the S-S bond affording thioamide. A variety of sensitive functional groups, including unprotected hydroxyl, carboxyl and difluoride substitution moieties, are well tolerated under the reaction conditions. Site-selective introduction of thioamide was further demonstrated for the biologically active molecule linkage, displaying the advantages compared with the conventional Lawesson’s reagent.