ABSTRACT Nicotinamide cofactors, NAD(P) + /NAD(P)H, act as indispensable mediators in nearly 80% of enzyme‐catalyzed redox reactions, playing a crucial role in the synthesis of chiral amine intermediates via imine reductases. However, their industrial application is hindered by dual constraints: the reliance on precious‐metal electron mediators and low selectivity toward 1,4‐NADPH. Herein, we report an interfacial‐engineered donor–acceptor (D–A) photocatalyst—oxygen‐doped carbon nitride nanosheets decorated with carbon nitride quantum dots (OCNF@CNQD)—for efficient mediator‐free NADPH regeneration. Within 60 min, the system achieved a regeneration activity of 70.1%, a 1,4‐NADPH selectivity of 78.0%, and a turnover frequency (TOF) of 1.22 mmol·g −1 ·h −1 , which places it at the forefront of reported catalysts. Mechanistic studies revealed that the D–A structure, together with the micro‐nanostructured flower morphology, promotes efficient charge separation and directional migration. Notably, hydroxyl and carboxyl groups on CNQD adsorb NADP + via hydrogen bonding, directing hydride transfer to the electrophilic C4 site of the nicotinamide ring, thereby enhancing 1,4‐NADPH selectivity. The catalyst was applied in a photoenzymatic cascade system, enabling the first asymmetric photoenzymatic reduction of 2‐(2,5‐difluorophenyl) pyrroline to afford an antitumor chiral amine intermediate (space–time yield: 351.0 µmol·g −1 ·h −1 ; conversion: 69.7%). This work introduces a synergistic electron‐hydrogen transfer regulation strategy for selective 1,4‐NAD(P)H regeneration and the sustainable synthesis of chiral amines.
Gong et al. (Thu,) studied this question.