Iridium-Catalyzed Direct and Site-Selective C–H Heteroarylation, Alkenylation, and Alkylation of Indoles

Indoles and coumarins represent prominent structural motifs in a wide range of biologically active molecules. Combining these two privileged scaffolds offers immense potential for innovation in drug discovery. Herein, we unveil a regioselective iridium-catalyzed approach for the direct C-H heteroarylation, alkenylation, and alkylation of indoles using iodonium ylides through a metal carbene-induced C-H insertion mechanism, accessing a series of novel 4-hydroxy-3-indolyl-coumarins and analogues. The method demonstrates a wide substrate scope, good tolerance for functional groups, scalability with low catalyst loading (as low as 0.2 mol %), and mild reaction conditions. Notably, Compound <b>3v</b> significantly enhanced GABA_ARs-α1β3γ2L activity, suggesting potential as a lead for antiepileptic and sedative drug discovery. Moreover, preliminary screening assays indicate that some other compounds exhibit moderate inhibitory effects against the pancreatic cancer cell line.