Enantioselective Nickel‐Catalyzed Hydrogenation of α‐Alkylidene Succinimides Enabled by Weak Noncovalent Interactions

Abstract The development of asymmetric hydrogenation catalysts based on Earth‐abundant metals presents a sustainable alternative to efficient but resource‐limited rare‐metal systems. However, these catalysts often suffer from low catalytic activity. In this study, through a combination of density functional theory (DFT) calculations and kinetic experiments, we uncovered a positive correlation between catalyst‐substrate weak noncovalent interactions and catalytic efficiency in the enantioselective nickel‐catalyzed hydrogenation of α‐alkylidene succinimides with different N ‐protecting groups. The tert ‐butyl ( t Bu) substituent emerged as the optimal choice, significantly enhancing reactivity. This approach enabled the hydrogenation of a wide range of substrates with excellent yields (up to 99%) and enantioselectivities (up to 99% ee), achieving a substrate/catalyst (S/C) ratio of 4000—twice the efficiency of rare‐metal catalysts (S/C ≤ 2000) for similar transformations. Energy decomposition analysis (EDA) of the enantiomers revealed that the high stereoselectivity is promoted by stabilizing weak noncovalent interactions in the R ‐configured transition state.