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

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 (2R,3R)- or (2S,3S)-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.