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A new and easily regenerable NAD(P)H model 9,10-dihydrophenanthridine (DHPD) has been designed for biomimetic asymmetric hydrogenation of imines and aromatic compounds. This reaction features the use of hydrogen gas as terminal reductant for the regeneration of the DHPD under the mild condition. Therefore, the substrate scope is not limited in benzoxazinones; the biomimetic asymmetric hydrogenation of benzoxazines, quinoxalines, and quinolines also gives excellent activities and enantioselectivities. Meanwhile, an unexpected reversal of enantioselectivity was observed between the reactions promoted by the different NAD(P)H models, which is ascribed to the different hydride transfer pathway. ■ INTRODUCTIONAs a couple of the most important coenzymes found in living cells, reduced nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) play great roles in reduction−oxidation (redox) metabolism. 1 Therefore, NAD(P)H mimics have become one of the most significant fields in biomimetic chemistry over the past few decades (Figure 1). Despite that much progress has been achieved, most of the current research focuses on the hydride transfer ability and selectivity in redox reactions rather than the renewable capability of NAD(P)H models. 2As one of the simplest NAD(P)H models, Hantzsch esters (HEH) 3 have been widely and successfully used as reductant in the enantioselective transfer hydrogenation of unsaturated bonds (CC, CN, and CO) using organocatalysts 4,5 and metal catalysts (Figure 1). 6 Recently, we reported an efficient method for in situ regeneration of HEH from Hantzsch pyridine under hydrogen gas in biomimetic asymmetric hydrogenation (Scheme 1). 7a Although excellent enantioselectivities were obtained, the regeneration condition of HEH was harsh, and the substrate scope was limited to benzoxazinones which underwent no background reaction. Developing a milder biomimetic asymmetric hydrogenation is of great interest in the field of NAD(P)H mimics and good for extending the substrate generality. Based on our previous work on asymmetric hydrogenation, 8 we envisioned that looking for a new and easily regenerable NAD(P)H model is probably a good choice.To the best of our knowledge, the dihydropyridine amido group is the key structure in NAD(P)H models and plays an important part in the hydride transfer process. Therefore, most of the currently successful NAD(P)H models, such as HEH 3 and 1-benzyl-1,4-dihydronicotinamide (BNAH), 9 contain a dihydropyridine skeleton. Based on the design of NAD(P)H models, the search of NAD(P)H models that can be used in the

The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds arguably presents one of the most attractive methods for the synthesis of chiral compounds. Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts. Much progress has been successfully achieved in the asymmetric reduction of imines, enamines, olefins, ketones and heteroarenes. It was also found that palladium catalyzed asymmetric hydrogenation could be used as a key step in tandem reactions to quickly synthesize chiral compounds. This tutorial review intends to offer an overview of recent progress in homogeneous palladium catalyzed asymmetric hydrogenation and should serve as an inspiration for further advances in this area. Key learning points(1) The general mechanism for homogeneous palladium catalyzed asymmetric hydrogenation.(2) The palladium catalysts' tolerance against acid, water and air in the hydrogenation process.(3) The substrate scopes and limitations in these transformations. (4) The common hydrogen sources used in these catalytic systems.(5) The general solvent-dependent phenomena in these transformations.