Dynamic Kinetic Resolution of Secondary Amines Using the 4CzIPN Photocatalyst and Candida Antarctica Lipase B

A radical-mediated hydrogen atom transfer (HAT) strategy by integrating a commercially available lipase CALB (Novozym 435) and an organic photocatalyst 4CzIPN into a chemoenzymatic system has been developed. The system establishes compatibility between 4CzIPN and CALB, enabling an efficient DKR process to directly convert racemic amines into chiral amides in high yields and excellent enantioselectivities. Mechanistic studies and control experiments reveal a synergistic DKR process. In this process, photocatalysis mediates single-electron transfer to generate thiyl radicals, which then facilitate the HAT process to induce the racemization of the unconverted enantiomer, thereby enabling a sequential CALB-catalyzed amidation to realize the high-yield synthesis of chiral amides. The developed protocol expands the scope of chiral amide synthesis, demonstrating the potential for broader applications.