Transition-metal-free synthesis of pyrimidines from lignin β-O-4 segments via a one-pot multi-component reaction

Heteroatom-participated lignin depolymerization for heterocyclic aromatic compounds production is of great importance to expanding the product portfolio and meeting value-added biorefinery demand, but it is also particularly challenging. In this work, the synthesis of pyrimidines from lignin beta-O-4 model compounds, the most abundant segment in lignin, mediated by NaOH through a one-pot multi-component cascade reaction is reported. Mechanism study suggests that the transformation starts by NaOH-induced deprotonation of C alpha-H bond in beta-O-4 model compounds, and involves highly coupled sequential cleavage of C-O bonds, alcohol dehydrogenation, aldol condensation, and dehydrogenative aromatization. This strategy features transition-metal free catalysis, a sustainable universal approach, no need of external oxidant/reductant, and an efficient one-pot process, thus providing an unprecedented opportunity for N-containing aromatic heterocyclic compounds synthesis from biorenewable feedstock. With this protocol, an important marine alkaloid meridianin derivative can be synthesized, emphasizing the application feasibility in pharmaceutical synthesis. Lignin depolymerization to make heterocyclic aromatic compounds is of great importance to expanding the product portfolio derived from biomass, but it is also particularly challenging. In this work, the authors report pyrimidine synthesis from lignin beta-O-4 model compounds via a one-pot multicomponent cascade reaction.