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

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.

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Journal
Nature Communications
Published
2026-03-04
DOI
https://doi.org/10.1038/s41467-026-70294-6
Primary Topic
Catalytic C–H Functionalization Methods
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Lanlan Zhang, Lintao Zeng, Tao Jiang, Xiuping Wang et al.
Nature Communications
Catalytic C–H Functionalization Methods
article

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

Lanlan Zhang, Lintao Zeng, Tao Jiang, Xiuping Wang, Chao Wang, Haohao Bai
article en

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.

Nature Communications
Tianjin Normal University (CN), Guangxi University (CN)
National Natural Science Foundation of China, Natural Science Foundation of Tianjin City
Openalex Percentile: Top 33%
Catalytic C–H Functionalization Methods
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