Thiourea Dioxide-Mediated N−O Bond Cleavage in Hydroxamic Acids for the Selective Synthesis of Primary Amides

Thiourea dioxide (TDO), a sustainable and cost-effective industrial compound, has been demonstrated as a bifunctional reagent for efficient hydroxyl activating and N-O bond cleavage of hydroxamic acids enabling the efficient synthesis of primary amides with excellent functional group compatibility. This straightforward process has been successfully applied to gram-scale synthesis of niacinamide. Furthermore, mechanistic studies suggested that the N-O bond cleavage involves a cascade process of sulfenylation and reduction. This novel and robust transformation gives a new lease of the synthetic utility of TDO as an innocuous and versatile reagent in organic chemistry.