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

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 (tBu) 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.