Testing the Limits: A Substrate Scope Analysis of a Photoenzymatic Cross-Electrophile Coupling

Abstract

Cross-electrophile coupling (XEC) has emerged as a promising method for the formation of C-C bonds. However, XECs traditionally require metal-based catalysts which often suffer issues with selectivity. Through photobiocatalysis, the integration of the high selectivity and sustainability of enzymes with photoredox chemistry which unlocks non-natural reactivity in flavin-dependent ‘ene’-reductases, previous studies accomplished an asymmetric sp3-sp3 XEC between nitroalkanes and a-chloro amides. The present work endeavors to utilize similar methods for the XEC of nitroalkanes and chloromethylpyridines, given the commonality of pyridines in desirable drug molecules. A substrate scope analysis was undertaken, investigating the XEC of nitroalkanes and chloromethylpyridines catalyzed by Caulobacter segnis ‘Ene’ Reductase (CsER) in the presence of cyan light. Yields for the substrate scope ranged from 1.6% to 42%, while enantioselectivities were upwards of 92:8 er.