Regioselective α-alkylation of benzo-fused cyclic amines via organic photoredox catalysis

Abstract

Addressing the synthetic challenge of regioselectively constructing benzo-fused 2-alkyl cyclic amines, this work presents an organophotoredox catalytic method for direct α-alkylation of tetrahydroquinolines, indolines, and related scaffolds with electronically unbiased styrenes. Employing a novel azafluoranthene-derived organic photosensitizer under visible-light irradiation, this transition-metal-free strategy enables efficient hydroaminoalkylation in mild conditions. The protocol exhibits exceptional substrate scope: diverse N-aryl and N-alkyl substituted benzo-fused amines (5–7 membered rings) couple with a series of olefins in up to 96% yield, while maintaining exclusive α-regioselectivity despite competitive C–H sites with near-identical bond dissociation energies. Gram-scale synthesis and concise routes to bioactive alkaloids (e.g., Galipeine, Cuspareine) underscore practical utility and adherence to green chemistry principles through high atom and step economy, and avoidance of precious metals.