Development of a Ligand for Cu-Catalyzed Amination of Base-Sensitive (Hetero)aryl Chlorides
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nihms-2123426.pdf
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Accepted version
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1.95 MB
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Author(s)
Ai, Han-Jun
Mai, Binh Khanh
Liu, Cecilia
Liu, Peng
Buchwald, Stephen L
Date Issued
October 13, 2025
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
Development of a Ligand for Cu-Catalyzed Amination of Base-Sensitive (Hetero)aryl Chlorides
Han-Jun Ai, Binh Khanh Mai, Cecilia Liu, Peng Liu, and Stephen L. Buchwald. Journal of the American Chemical Society 2025 147 (42), 38275-38282.
Version
Author's final manuscript
Abstract
We report a new N1,N2-diarylbenzene-1,2-diamine ligand, L6, that supports a copper catalyst capable of coupling base-sensitive aryl chlorides and amines that were previously unsuccessful substrates for Cu-catalyzed C–N coupling. A detailed structure–activity relationship study, combined with density functional theory (DFT) calculations, was used to uncover two key structural features that contribute to the efficacy of the catalyst derived from L6. First, steric repulsion caused by a methyl substituent induces a conformational change that opens up additional space for ligand deprotonation and oxidative addition. Second, the trifluoromethyl groups create electrostatic interactions between the ligand and aryl chloride substrates that facilitate oxidative addition via through-space ligand–substrate interaction.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
10.1021/jacs.5c10910
