Photo-driven bifunctional iron-catalyzed one-pot assembling of indoles from arylamines and alkanes/carboxylic acids
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(sp<sup>3</sup>)-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.
Authors
- Yunhe Jin
- Hui Zi
- Wenlong He
- Ran Xu
- Shuyang Liu
- Lifang Wang
- Ziyu Gan
- Jian Gao
- Fangyi Qu
Institutions
- Dalian University of Technology (CN)
- Dalian University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-08
- DOI
- https://doi.org/10.1038/s41467-025-68208-z
- Citations
- 2
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 45.90
Funders
- Natural Science Foundation of Liaoning Province
- Fundamental Research Funds for the Central Universities