Cobalt-Catalyzed Synthesis of Pyrrolidinones from Nitriles and Acrylamides

Significance

The synthesis of pyrrolidinone derivatives 3 via the cobalt-catalyzed reductive coupling of acrylamides 1 and nitriles 2 is reported. Various N-alkyl acrylamides were found to participate efficiently in the reaction. One example of an N-phenyl acrylamide was also reported; however, the yield was only moderate (58%). A variety of nitriles were used, including acetonitrile and higher homologues. Arylacetonitriles bearing EDGs and EWGs were equally well tolerated. The authors present a plausible mechanism involving initial ­reduction of Co(III) to Co(I) by zinc, followed by ­cyclometalation to give 4. Hydrolysis and subsequent ketoamide cyclization and dehydration delivers the product. The role of ZnI₂ is unclear, ­although its participation as a Lewis acid is likely.