Recent advances in green multi-component reactions for heterocyclic compound construction

Abstract

Multi-component reactions (MCRs) are processes in which three or more reactants are introduced into one pot to obtain the final product with high atom efficiency, and in recent years, these have become a key strategy for advancing more sustainable processes in modern synthetic communities and the pharmaceutical industry. Meanwhile, minimizing the use of solvents, catalysts, time, reagents, and waste is essential during green chemical synthesis to reduce cost and environmental impact. Heterocycles are ubiquitous and have thus prompted the development of numerous methods for their synthesis. Among various strategies, MCRs represent one of the most promising routes for the synthesis of heterocyclic moieties such as quinolines, quinazolines, pyrimidines and imidazoles, which are widely recognized in nature and clinical evaluation. To promote greener syntheses, a significant body of literature detailing the synthesis of these biologically important compounds via environmentally friendly MCRs has emerged. This review focused on the recent advances in the green approach to preparing heterocyclic compounds via MCRs. These green approaches included photoredox catalysis, electrochemical activation, catalyst-free methods, and the use of water as the sole green solvent, reported between 2018 and 2024, highlighting their strengths and limitations. The synthesis of different types of heterocycles via green MCRs was covered. The substrate scope, reaction conditions, yields and mechanisms were also examined and discussed.