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Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2

Author:
Tan, Xuefeng, Gao, Shuang, Zeng, Weijun, Xin, Shan, Yin, Qin, Zhang, Xumu
Source:
Journal of the American Chemical Society 2018 v.140 no.6 pp. 2024-2027
ISSN:
1520-5126
Subject:
amination, ammonium acetate, ammonium salts, drugs, hydrogen, ketones, ligands, primary amines, reducing agents
Abstract:
A ruthenium/C₃-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H₂ as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C₃-TunePhos is also presented.
Agid:
6038635