1. Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines.
- Author
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Chen JJ, Fang JH, Du XY, Zhang JY, Bian JQ, Wang FL, Luan C, Liu WL, Liu JR, Dong XY, Li ZL, Gu QS, Dong Z, and Liu XY
- Subjects
- Amides chemistry, Ligands, Pharmaceutical Preparations chemistry, Alkylation, Amines chemistry, Catalysis, Copper chemistry
- Abstract
Chiral amines are commonly used in the pharmaceutical and agrochemical industries
1 . The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods1,2 . 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 version3-5 . 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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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