Abstract
(Iso)quinolines are among the most common heterocycles in US Food and Drug Administration approved drugs, whereas benzoazepines are underrepresented in drug discovery libraries, primarily because of the lack of efficient preparation routes. Therefore, an efficient method of converting (iso)quinolines to benzoazepines by leveraging the chemistries unique to (iso)quinolines to access diverse benzoazepines should be valuable. Herein, we report a mechanochemical skeletal editing protocol for use in carbon-atom insertion into (iso)quinolines to afford the corresponding benzoazepines. This reaction proceeds readily under ambient conditions without the need for metal additives, bulk solvent, or complicated pre-activation processes. Using this user-friendly protocol, we investigate substrate scope, and reaction mechanism. Moreover, benzoazepines undergo light-induced cycloaddition to yield cyclobutene-fused indolines, which can be converted to indoles by selectively removing carbon atoms. The utility of this skeletal transform is further demonstrated through the skeletal editing of pharmaceutically relevant (iso)quinolines.
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Acknowledgements
We thank Wei Sun for his assistance with the NMR experiments. We also thank Tianyang Yu for his support with data analysis.
Funding
H.W. discloses support for the research of this work from the National Natural Science Foundation of China (22271231), and the Natural Science Basic Research Plan in Shaanxi Province of China (2024SF-YBXM-419). Z. Z. discloses support for the research of this work from Shaanxi Fundamental Science Research Project for Chemistry and Biology (22JHO005).
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Jing, C., Huang, F., Liang, X. et al. Mechanochemical Single-Carbon Insertion into (Iso)quinolines. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73831-5
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DOI: https://doi.org/10.1038/s41467-026-73831-5
