Rh(III) Catalyzed C2 Annulation of Indoles With 1,4‐Quinones: Rapid Access to Imidazo[1,5‐ a ]Indole and Benzo[5,6][1,3]Oxazino[3,4‐ a ]Indole Scaffolds

Rh(III)-catalyzed regioselective C─H functionalization of N-acetyl-1H-indole-1-carboxamides with 1,4 quinones serving as both C1 and C3 synthons has been established. By tuning reaction conditions, two distinct C─H functionalization modes were enabled. The N-acetyl amide group(directing group (DG)) exhibits mercurial behavior; the amide nitrogen functions as a nucleophilic site in the [4 + 1] annulation, while the amide carbonyl carbon serves as an electrophilic site in the [3 + 3] cyclization. By contrast, 1,4-quinones display the reverse reactivity pattern. This duality facilitates two divergent modifications through DG-retained-coupled and DG-partially eliminated-coupled pathways, which deliver the valuable penta-spiro/fused heterocycles. In the presence of NaOAc, alkenylation followed by aromatization enables intramolecular nucleophilic addition of installed FG onto the carbonyl group of DG, delivering the FG-DG [3 + 3] cyclized product. The catalytic mechanism, further studied through experimental studies, covers the characterization of the rhodacycle intermediate. This protocol feature tunable regioselectivity, broad substrate scope, good to high yields, compatibility with diverse functional groups, and versatile synthetic modifications, thus offering a robust approach to valuable bioactive imidazo- and benzoxazino-fused indole analogues.