Unlocking Efficient Spontaneous Deracemization: A MOF‐Mediated Heterogeneous System Overcomes Catalytic Incompatibility in Cocrystallization

Abstract

ABSTRACT Cocrystallization‐induced deracemization is a powerful route to enantiopure pharmaceuticals, yet is hindered by detrimental interactions between homogeneous catalysts and chiral components. Herein, we report a novel heterogeneous catalysis strategy using metal–organic frameworks (MOFs) to overcome this compatibility challenge. By encapsulating the base catalyst 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) into ZIF‐8, we created a ZIF‐8@DBU composite catalyst, that effectively isolates the catalyst while preserving its racemization activity. This enabled the efficient deracemization of racemic DMY via cocrystallization, selectively yielding either the (2 R ,3 R )‐ or (2 S ,3 S )‐enantiomer simply by switching the handedness of the coformer, N‐benzyl‐1‐phenylethylamine (NBP). Remarkably, the product yield reached up to 52%, surpassing the 50% theoretical limit of conventional chiral resolution techniques. The strategy proved general, extending successfully to ZIF‐67@DBU and ZIF‐90@DBU. This work demonstrates the feasibility of using tailored MOF composites to overcome long‐standing compatibility barriers in deracemization and opens avenues for their broader application in asymmetric synthesis.