Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines

Chen，Ji Jun1; Fang，Jia Heng1; Du，Xuan Yi1; Zhang，Jia Yong1; Bian，Jun Qian1; Wang，Fu Li1; Luan，Cheng2; Liu，Wei Long1; Liu，Ji Ren1; Dong，Xiao Yang1; Li，Zhong Liang2; Gu，Qiang Shuai2; Dong，Zhe1; Liu，Xin Yuan1

2023-06-08

10.1038/s41586-023-05950-8

Nature   Impact Factor & Quartile

0028-0836

1476-4687

Chiral amines are commonly used in the pharmaceutical and agrochemical industries. The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods. Although the N-alkylation of aliphatic amines with alkyl halides has been widely adopted for over 100 years, catalyst poisoning and unfettered reactivity have been preventing the development of a catalyst-controlled enantioselective version. Here we report the use of chiral tridentate anionic ligands to enable the copper-catalysed chemoselective and enantioconvergent N-alkylation of aliphatic amines with α-carbonyl alkyl chlorides. This method can directly convert feedstock chemicals, including ammonia and pharmaceutically relevant amines, into unnatural chiral α-amino amides under mild and robust conditions. Excellent enantioselectivity and functional-group tolerance were observed. The power of the method is demonstrated in a number of complex settings, including late-stage functionalization and in the expedited synthesis of diverse amine drug molecules. The current method indicates that multidentate anionic ligands are a general solution for overcoming transition-metal-catalyst poisoning.

SCI ; IC ; CCR

English

NI Journal Papers ; ESI Highly Cited Papers ; NI论文

First ; Corresponding

National Key R&D Program of China["2021YFF0701604","2021YFF0701704"] ; National Natural Science Foundation of China["22025103","92256301","21831002"] ; Guangdong Innovative Program[2019BT02Y335] ; Guangdong Innovative and Entrepreneurial Research Team Program[2021ZT09C278] ; Guangdong Provincial Key Laboratory of Catalysis[2020B121201002] ; Shenzhen Science and Technology Program["KQTD20210811090112004","JCYJ20200109141001789"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000999106200001

NATURE PORTFOLIO

BIOLOGY & BIOCHEMISTRY;CLINICAL MEDICINE;MULTIDISCIPLINARY;PLANT & ANIMAL SCIENCE;ENVIRONMENT/ECOLOGY;SOCIAL SCIENCES, GENERAL;MICROBIOLOGY;ECONOMICS BUSINESS;IMMUNOLOGY;MATERIALS SCIENCE;COMPUTER SCIENCE;SPACE SCIENCE;MOLECULAR BIOLOGY & GENETICS;CHEMISTRY;NEUROSCIENCE & BEHAVIOR;PHYSICS;GEOSCIENCES;ENGINEERING

2-s2.0-85159140752

Scopus

1.Shenzhen Grubbs Institute and Department of Chemistry,Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,China
2.Academy for Advanced Interdisciplinary Studies and Department of Chemistry,Southern University of Science and Technology,Shenzhen,China

Chen，Ji Jun,Fang，Jia Heng,Du，Xuan Yi,et al. Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines[J]. Nature,2023,618(7964):294-300.

Chen，Ji Jun.,Fang，Jia Heng.,Du，Xuan Yi.,Zhang，Jia Yong.,Bian，Jun Qian.,...&Liu，Xin Yuan.(2023).Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines.Nature,618(7964),294-300.

Chen，Ji Jun,et al."Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines".Nature 618.7964(2023):294-300.