Peroxygenase Enabled Reductive Kinetic Resolution for the Enantioenrichment of Organoperoxides

Enantiomerically pure organoperoxides serve as valuable precursors in organic transformations. In this study, we present the first examples of unspecific peroxygenase‐catalyzed kinetic resolution of racemic organoperoxides through asymmetric reduction. Through meticulous investigation of the reaction conditions, it is shown that the unspecific peroxygenase from Agrocybe aegerita (AaeUPO) exhibits robust catalytic activity in the kinetic resolution reactions of the model substrate with turnover numbers up to 60000 and turnover frequency of 5.6 s‐1. Various aralkyl organoperoxides were successfully resolved by AaeUPO, achieving excellent enantioselectivities (e.g., up to 99% ee for the (S)‐organoperoxide products). Additionally, we screened commercial peroxygenase variants to obtain the organoperoxides with complementary chirality, with one mutant yielding the (R)‐products. While unspecific peroxygenases have been extensively demonstrated as a powerful oxidative catalyst, this work highlights its usefulness in catalyzing the reduction of organoperoxides and providing versatile chiral synthons.