Chemoselective Thioamidation of Potassium Acyltrifluoroborates (KATs) and Amines Using Elemental Sulfur in Aqueous Solution

Bioisosteres serve as valuable design elements for medicinal chemists, enabling the adjustment of the structural and pharmacokinetic properties of bioactive compounds to develop viable drug candidates. Thioamides hold promise as bioisosteres for the commonly used amide pharmacophores. This article presents a synthesis method for thioamides, achieved through the reaction of potassium acyltrifluoroborates with amines in the presence of elemental sulfur in aqueous solution. The process is simple, mild, and accommodates various polar functional groups, making it ideal for creating amide and thioamide drug libraries. Furthermore, seven bioactive thioamides and their corresponding marketed drug analogs have been synthesized using present method.