Asymmetric Transfer Hydrogenation of Stable NH Imines for the Synthesis of Enantiopure α‐Chiral Primary Amines

• Published in: Chinese journal of chemistry 2024-09, Vol.42 (18), p.2211-2216
• Main Authors: Zhang, Mangang, Li, Hui, Wu, Keqin, Rong, Nianxin, Lin, Shaoquan, Yang, Hua, Yin, Qin
• Format: Article
• Language: English
• Subjects: 2‐(1‐Aminoalkyl)anilines; Amines; Ammonia; Aniline; Asymmetric hydrogenation; Asymmetric transfer hydrogenation; Asymmetry; Biocompatibility; Catalysis; Catalysts; Condensates; Functional groups; Hydrogenation; Imines; NH imines; α‐Chiral primary amine
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202400338

Comprehensive Summary Although it offers a direct route to access synthetically valuable α‐chiral primary amines, asymmetric transfer hydrogenation of NH imines has been rarely studied, due in large part to the inaccessibility and instability of NH imines. Herein, we report a Rh‐catalyzed asymmetric transfer hydrogenation of a kind of novel and stable NH imines which are prepared via condensation of easily available sulfonylated 2’‐aminoacetophenones with NH3 in methanol. With this method, enantioenriched chiral 2‐(1‐aminoalkyl)anilines, which are privileged pharmacore groups, have been synthesized with good functional group compatibility, and with up to 99% ee. A gram‐scale reaction using 0.2 mol% of catalyst has been successfully performed to highlight the practicality. Furthermore, the products can be derivatized into enantiopure bioactive molecules as well as chiral tridentate ligands for metal catalysis. Herein, we report a Rh‐catalyzed asymmetric transfer hydrogenation of NH imines, which produces synthetically versatile and enantioenriched 2‐(1‐aminoalkyl)anilines with up to 99% ee. A gram‐scale reaction using 0.2 mol% of catalyst has been successfully achieved. Furthermore, the products can be derivatized into bioactive molecules as well as chiral tridentate ligands for metal catalysis.