Synthesis of α-keto thioamides via oxidative thioamidation of α-amino carbonyls using hypervalent iodine under neat conditions

Abstract

An efficient and exceptional method for cleaving the C–N bond in α-amino carbonyl compounds has been developed using N,N,N′,N′-tetraalkylthiuram disulfides (TATDs), iodine(III) reagent phenyliodine diacetate (PIDA), and N,N-diisopropylethylamine. The PIDA reagent effectively facilitates an oxidative thioamidation process, affording α-keto thioamide derivatives in high yields under solvent-free (neat) conditions. This approach enables the synthesis of α-keto thioamides through a sequence of CS and C–N bond formations. Additionally, this protocol offers several advantages, including a metal-free process, broad substrate compatibility, and suitability for large-scale synthesis. Notably, this method has the potential for synthesizing biologically relevant α-keto thioamides.