Sc(OTf)3-catalyzed synthesis of anhydrides from twisted amides

Abstract

A novel synthesis of anhydrides from twisted amides is reported. Sc(OTf)₃ catalysis in the presence of water is used to synthesize anhydrides in one step from amides without external nucleophiles. Mechanistic studies indicate that the coordination of the catalyst is critical to induce the challenging N–C activation step. This process further highlights the utility of twisted amides in organic synthesis. Notably, the reaction indicates that twisted amides based on the glutarimide scaffold are more reactive than carboxylic acid anhydrides under the developed conditions, which opens the door to controlled sequential catalysis through amide N–C bond cleavage.