Photoinduced Palladium-Catalyzed Decarboxylative Radical Cross Coupling Reaction of Secondary Amides with α-Keto...

Developing sustainable methods for C-N bond formation is crucial for drug discovery. Visible-light-induced palladium-catalyzed decarboxylative radical cross coupling of isoxazole carboxamides with α-keto acids is developed for the synthesis of pharmaceutically important imides. Chelation-assisted coupling reaction proceeded efficiently at room temperature and the products were obtained in good to excellent yields. The salient features of this protocol are readily accessible and nontoxic materials, expensive Ir or Ru photocatalyst-free mild reaction conditions, broad substrate scope, tolerance to air and moisture and operational simplicity. Gram scale synthesis, further manipulation of products and late-stage functionalization of drug and peptide molecules were illustrated to show the practicality and versatility of the method. A mechanism involving acyl radical generation from α-keto acids and subsequent palladium-catalyzed coupling with secondary amides is proposed on the basis of the control experiments.