Stereodivergent synthesis of chiral amines bearing vicinal stereocenters via hydroamination of trisubstituted alkenes

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Authors: Haohao Bai, Mingchao Li, Xiuping Wang, Tao Jiang, Lintao Zeng, Lanlan Zhang, Chao Wang
Cited by: 3
References: 58

Abstract

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.

Fields of Study & Subjects

Catalytic C–H Functionalization Methods Asymmetric Hydrogenation and Catalysis Catalytic Alkyne Reactions

Publication details

Journal / source
Nature Communications
Publisher
Springer Science and Business Media LLC
Volume
17
Issue
1
Publication date
4 March 2026
Language
EN