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Copper-catalyzed C(sp)–H aryl amination enables modular synthesis of quinolines and 2-quinolinones

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Abstract

Herein, we disclose a novel copper-catalyzed C(sp)–H aryl amination of terminal alkynes with anthranils, enabling the rapid generation of highly reactive secondary N-aryl ynamines for the modular synthesis of structurally diverse C2-substituted quinolines and 2-quinolinones. The in-situ formed carbonyl-ynamines are prone to tautomerize to carbonyl-ketenimines, which can efficiently react with a series of nucleophiles, including amines, alcohols, phenols, thiols, thiophenols, active-methylene compounds, and even water to produce various quinoline derivatives with the generation of H2O as a sole and green byproduct. This method also unlocks a practical route to create various quinoline-fused heterocycles and can be successfully applied to the late-stage modification of complex molecules and the concise synthesis of bioactive targets. Mechanistic studies reveal a copper-catalyzed inner-sphere nitrene transfer process by using anthranils as novel aryl nitrene precursors.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22271065, 22271314), and the Guangzhou Basic and Applied Research (202201010396).

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Authors and Affiliations

  1. School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China

    Yang Gao, Haixia Li, Simin Yang, Yanping Huo, Qian Chen, Xianwei Li & Zhe Wang

  2. Jieyang Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Jieyang, 515200, China

    Yang Gao

  3. Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education & Hubei Key Laboratory of Catalysis and Materials Science, School of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, 430074, China

    Xiao-Qiang Hu

Authors
  1. Yang Gao
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  2. Haixia Li
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  3. Simin Yang
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  6. Xianwei Li
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  8. Xiao-Qiang Hu
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Correspondence to Yang Gao or Xiao-Qiang Hu.

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Supporting information The supporting information is available online at chem.scichina.com and link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Gao, Y., Li, H., Yang, S. et al. Copper-catalyzed C(sp)–H aryl amination enables modular synthesis of quinolines and 2-quinolinones. Sci. China Chem. 67, 595–603 (2024). https://doi.org/10.1007/s11426-023-1739-y

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