Regiocontrolled One-Step Indole Synthesis from Carbonyl Compounds via Organobismuth Chemistry

Abstract

Indoles are privileged scaffolds in natural products, pharmaceuticals, and synthetic intermediates, and their concise, regioselective synthesis remains an enduring challenge. Here, we report a one-step indole synthesis enabled by 2-aminophenyl-tBuBisTrip (aryl–BisTrip) (2), a bismuth(V) reagent that effects rapid α-arylation of lithium enolates followed by spontaneous annulation. The method is effective for a wide range of cyclic and acyclic ketones, including challenging cyclopentanones and heterocyclic substrates, as well as 1,2- and 1,3-dicarbonyl compounds and enolates derived from silyl enol ethers. Notably, the platform enables direct indole annulation of enones, a substrate class that has remained problematic via Fischer or transition-metal-catalyzed methods. The utility of the transformation is further illustrated by late-stage indole installation on complex bioactive molecules and by a desymmetrization sequence that translates asymmetric deprotonation into chiral indole synthesis. Together, these results establish a general main-group-enabled approach for regiocontrolled indole construction from simple carbonyl precursors.