Photo-driven bifunctional iron-catalyzed one-pot assembling of indoles from arylamines and alkanes/carboxylic acids.

Wang, Lifang; Liu, Shuyang; Zi, Hui; Xu, Ran; Qu, Fangyi; He, Wenlong; Gan, Ziyu; Gao, Jian et al. · Nat Commun · 2026

basic_science · Level V

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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(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.