Successive Cleavage and Reconstruction of Lignin β-O-4 Models and Polymer to Access Quinoxalines

Abstract

The construction of N-heterocyclic compounds from lignin remains a great challenge due to the complex lignin structure and the involvement of multiple steps, including the cleavage of lignin C-O linkages and the formation of heterocyclic aromatic rings. Herein, the first example of KOH mediated sustainable synthesis of quinoxaline derivatives from lignin β-O-4 model compounds in a one-pot fashion under transition-metal-free conditions has been achieved. Mechanistic studies suggested that this transformation includes highly coupled cascade steps of cleavage of C-O bonds, dehydrative condensation, sp³ C-H bond oxidative activation, and intramolecular dehydrative coupling reaction. With this protocol, a wide range of functionalized quinoxalines, including an important drug compound AG1295, were synthesized from lignin β-O-4 model compounds and β-O-4 polymer, showcasing the application potential of lignin in pharmaceutical synthesis.

Keywords: N-heterocyclic compounds; biomass; lignin; quinoxalines; transition-metal-free.