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Rh(II)-catalyzed intermolecular carboamination of pyridines via double Csp2–H bond activations

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Abstract

We disclose the development of the Rh-catalyzed amine-directed remote 5,6-carboamination protocol of pyridines via dual Csp2–H functionalizations. A variety of readily available 2-aminopyridines and 1,2,3-triazoles are allowed for coupling cyclization to access polyfunctionalized azaindoles. Mechanistic studies including DFT calculations unveil that relay carbenoid-electrophilic addition to pyridines and the sequential pyridyl Csp2–H amination are involved in this transformation. The post-synthetic utility of this methodology is showcased by versatile and site-selective modification of azaindoles.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22271100, 21973113), the Key-Area Research and Development Program of Guangdong Province (2020-B010188001), the Guangdong Basic and Applied Basic Research Foundation (2023A1515010070), and the China Postdoctoral Science Foundation (2021M701243).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, China

    Zhongfeng Luo, Fengjuan Chen, Huanfeng Jiang & Wei Zeng

  2. School of Materials Science and Engineering, PCFM Lab, Sun Yat-sen University, Guangzhou, 510275, China

    Jingxing Jiang, Xiaoyu Zhou & Zhuofeng Ke

  3. Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China

    Lifang Zou & Junshan Liu

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  1. Zhongfeng Luo
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  2. Jingxing Jiang
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  3. Lifang Zou
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  4. Xiaoyu Zhou
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  5. Junshan Liu
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  6. Zhuofeng Ke
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  7. Fengjuan Chen
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  8. Huanfeng Jiang
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  9. Wei Zeng
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Corresponding authors

Correspondence to Junshan Liu, Zhuofeng Ke, Fengjuan Chen or Wei Zeng.

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Conflict of interest The authors declare no conflict of interest.

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Supporting information The supporting information is available online at https://chem.scichina.com and https://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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Luo, Z., Jiang, J., Zou, L. et al. Rh(II)-catalyzed intermolecular carboamination of pyridines via double Csp2–H bond activations. Sci. China Chem. 67, 374–382 (2024). https://doi.org/10.1007/s11426-023-1785-1

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  • DOI: https://doi.org/10.1007/s11426-023-1785-1

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