In a significant advance in asymmetric catalysis, a research team led by Jianrong Steve Zhou at Peking University Shenzhen Graduate School has developed a highly enantioselective nickel-catalyzed reductive alkenylation of N-sulfonyl and N-sulfamoyl aldimines using readily available alkenyl bromides and triflates. The study provides a practical and scalable route to chiral benzylic amines, important building blocks in pharmaceuticals and biologically active molecules.
Despite significant progress in asymmetric imine functionalization, the direct enantioselective incorporation of alkenyl groups using simple electrophiles has remained challenging, particularly under mild conditions with broad functional-group tolerance. The newly developed nickel/bis(oxazoline) catalytic system addresses these limitations by enabling efficient reductive coupling under nearly neutral conditions with excellent enantioselectivity and broad substrate scope.
The method is compatible with a wide range of functional groups, including esters, heterocycles, and weakly acidic alcohols. Notably, the transformation proceeds with very low catalyst loadings (as low as 0.2 mol%) and can be readily scaled up without erosion of yield or enantioselectivity.
Mechanistic investigations supported by density functional theory (DFT) calculations suggest a classical 1,2-migratory insertion pathway at the nickel center, which accounts for the observed high levels of stereocontrol.
The resulting chiral alkenylated amines can be further diversified through hydrogenation and other derivatization reactions, providing access to structurally diverse saturated amines and expanding the chemical space of chiral amine scaffolds.
Overall, this work establishes a robust and scalable strategy for asymmetric reductive alkenylation and highlights the growing potential of nickel catalysis in enantioselective C–C bond-forming reactions.
