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

An efficient and exceptional method for cleaving the C-N bond in α-amino carbonyl compounds has been developed using <i>N</i>,<i>N</i>,<i>N</i>',<i>N</i>'-tetraalkylthiuram disulfides (TATDs), iodine(III) reagent phenyliodine diacetate (PIDA), and <i>N</i>,<i>N</i>-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 CS 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.