Peroxygenase‐Enabled Reductive Kinetic Resolution for the Enantioenrichment of Organoperoxides

Abstract Enantiomerically pure organoperoxides serve as valuable precursors in organic transformations. Herein, 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 ( Aae UPO) 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 Aae UPO, 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 catalysts, this study highlights their usefulness in catalyzing the reduction of organoperoxides and providing versatile chiral synthons.