Abstract
Indoles are privileged structural motifs in N-heterocyclic chemistry, while developing a general and facile platform capable of directly transforming commodity chemicals into multi-functionalized indoles persists as an unmet challenge. Herein, we present a photo-driven bifunctional iron-catalyzed strategy for one-pot synthesis of indoles from readily available arylamines and alkanes/carboxylic acids. By leveraging a synergistic combination of iron-based photocatalysis via ligand-to-metal charge transfer pathway and Lewis acid catalysis, the method enables efficient C(sp3)–H activation or decarboxylation followed by sigmatropic rearrangement cyclization under mild conditions. The protocol demonstrates broad substrate scope (152 examples), excellent functional group tolerance, and high yields (up to 95%), facilitating the direct construction of diverse indole scaffolds without pre-functionalization. Notably, the methodology can be successfully applied to the concise and scale-up total synthesis of several pharmacologically relevant indole derivatives, including Iprindole, Mebhydrolin, Melatonin, and A-FABP inhibitor, underscoring its practicality and potential for industrial application in pharmaceutical manufacturing.
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All data that support the findings of this study are provided within the paper and its supplementary information files, and are also available from the corresponding author upon request.
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Acknowledgements
We acknowledge the assistance of Dr. Huihui Wan and Dr. Yuming Sun in the DUT Instrumental Analysis Center for their great help in HRMS analysis. We acknowledge the support of the Natural Science Foundation of Liaoning Province (2024-MSLH-080 for Y.J.), the National College Student Innovation Training Program (20251014110304 for J.G., 20241014110019 for Y.J.), the Fundamental Research Funds for the Central Universities (DUT24BK042 for Y.J.), and the Young Teachers Incentive Project from the School of Chemistry @DUT (for Y.J.).
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Y.J. led this project. L.W. and Y.J. conceived and designed the experiments. L.W., S.L., H.Z., R.X., F.Q., W.H., Z.G., and J.G. performed and analyzed the experiments. L.W., S.L., and Y.J. wrote and revised the manuscript. All authors discussed the results and contributed to the manuscript.
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Wang, L., Liu, S., Zi, H. et al. Photo-driven bifunctional iron-catalyzed one-pot assembling of indoles from arylamines and alkanes/carboxylic acids. Nat Commun (2026). https://doi.org/10.1038/s41467-025-68208-z
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DOI: https://doi.org/10.1038/s41467-025-68208-z
