Oxidative cross-dehydrogenative coupling (CDC) via C(sp2)–H bond functionalization: tert-butyl peroxybenzoate (TBPB)-promoted regioselective direct C-3 acylation/benzoylation of 2H-indazoles with aldehydes/benzyl alcohols/styrenes

Abstract

An efficient, cost-effective, transition-metal-free, oxidative C_(sp²)–H/C_(sp²)–H cross-dehydrogenative coupling via a C_(sp²)–H bond functionalization protocol for the regioselective direct C-3 acylation/benzoylation of substituted 2H-Indazoles 1a–m with substituted aldehydes 2a–q/benzyl alcohols 5a–e/styrenes 6a–e is reported. The operationally simple protocol proceeds in the presence of tert-butyl peroxybenzoate (TBPB) as an oxidant in chlorobenzene (PhCl) as a solvent at 110 °C for 24 h under an inert atmosphere, which furnished a diverse variety of substituted 3-(acyl/benzoyl)-2H-indazoles 3a–q/4a–l in up to 87% yields. The reaction involves a free-radical mechanism and proceeds via the addition of an in situ generated acyl radical (from aldehydes/benzyl alcohols/styrenes) on 2H-indazoles. The functional group tolerance, broad substrate scope, control/competitive experiments and gram-scale synthesis and its application to the synthesis of anti-inflammatory agent 11 and novel indazole-fused diazepine 13 further signify the versatile nature of the developed methodology.