Microwave-Assisted Copper-Mediated One-Pot Sequential Synthesis of Quinolino[3,4-b]quinoxalines

Abstract

An efficient microwave-assisted one-pot protocol has been developed for the synthesis of 6-aryl/heteroarylquinolino[3,4-‍b]quinoxaline derivatives. The method involves a CuI-mediated tandem annulation of 2-(2-bromophenyl)quinoxalines with aryl and heteroaryl aldehydes, using TMSN₃ as the nitrogen source. The transformation proceeds rapidly under microwave irradiation, delivering the desired products in moderate-to-excellent yields (up to 91%) with broad substrate scope. Further, benzyl alcohols (with TBHP) also serve as viable precursors under identical conditions to afford 6-aryl/heteroaryl-quinolino[3,4-b]quinoxaline derivatives. Notably, the protocol eliminates the requirement for a stoichiometric amount of reducing agent used in the earlier protocol. It can be extended to gram-scale synthesis with a remarkably reduced reaction time. Mechanistic investigations, supported by control experiments, ESI-HRMS analysis, and DFT calculations, provide insight into the reaction pathway. This approach offers a rapid, practical, and scalable route to quinolino[3,4-b]quinoxaline frameworks of potential medicinal relevance.