Stereodivergent synthesis of chiral amines bearing vicinal stereocenters via hydroamination of trisubstituted alkenes
2026-03-04
Chiral aliphatic amines bearing vicinal stereocenters are prevalent motifs in pharmaceuticals and bioactive molecules, yet efficient and stereodivergent access to these structures remains a longstanding challenge. Herein, we report a nickel-catalyzed enantioselective hydroamination of acyclic trisubstituted alkenes that provides a unified platform for the stereodivergent construction of chiral amines bearing β,γ-stereocenters. The reaction exhibits broad substrate scope, accommodating diverse amine electrophiles and tri-substituted alkenes, including those derived from complex bioactive molecules, with high levels of regio-, diastereo-, and enantioselectivity. By modulating the alkene geometry and the configuration of a chiral biimidazoline ligand, all four stereoisomers can be accessed in a predictable manner. The protocol proceeds under mild conditions, tolerates various functional groups, and enables late-stage derivatization, demonstrating its utility for constructing densely functionalized, three-dimensional amine scaffolds. This work provides a valuable platform for asymmetric synthesis and holds strong potential for drug discovery and molecular design.