Abstract In situ H 2 ‐driven NAD(P)H regeneration offers a sustainable approach for chemoenzymatic reduction in vitro; however, low selectivity in NAD(P)H formation, coupled with mutual deactivation between chemical catalysts and enzymes, severely compromises efficiency. Herein, we report the development of an oil‐in‐water Pickering emulsion microreactor leveraging an interfacial π–π stacking interaction to enable directional H* transfer, achieving >99% selectivity in NADH regeneration. By further coupling this NADH regeneration system with horse liver alcohol dehydrogenase (HLADH) catalyzed asymmetric reductive resolution of racemic 2‐phenylpropionaldehyde to ( S )‐(‐)‐2‐phenyl‐1‐propanol, a chemoenzymatic Pickering emulsion microreactor was constructed, which smoothly catalyzed the H 2 ‐driven reductive resolution reaction and achieved an ee value >99% with more than 2000 NADH regeneration cycles, representing a highest value ever reported for in situ H 2 ‐driven NADH regeneration. The efficiency of this chemoenzymatic microreactor is attributed to the high NADH selectivity and spatial separation of metal catalysts and HLADH. Insight into modulating mass transfer through noncovalent interactions and mitigating mutual deactivation of incompatible catalysts by spatial separation is promising for the development of efficient chemoenzymatic microreactors in sustainable chiral chemical production.
Lan et al. (Fri,) studied this question.