Metal–Organic Framework (MOF)-Based Catalytic Systems for Multicomponent Reactions in Sustainable Heterocycle Synthesis: Recent Advances, Mechanistic Insights, and Future Perspectives

Metal–organic frameworks (MOFs) have emerged as versatile heterogeneous catalytic platforms for multicomponent reactions (MCRs), enabling the one-pot synthesis of structurally diverse heterocyclic compounds. Their high specific surface areas, tunable pore environments, well-defined coordination structures, and chemically modifiable active sites provide opportunities to regulate substrate adsorption, activation, diffusion, and product formation. Recent studies have employed MOF-based catalytic systems for the synthesis of pyridines, pyrimidines, pyrans, tetrazoles, pyranopyrazoles, imidazoles, quinolines, triazoles, and spirocyclic heterocycles. This review summarizes recent developments in MOF-based MCRs, with emphasis on catalyst structure, catalytic function, substrate scope, reaction conditions, recyclability, and proposed mechanistic pathways. Attention is given to the relationships among metal nodes, organic linkers, pore architecture, surface functionalization, active-site accessibility, and catalytic performance. The review also examines green-chemistry considerations, including one-pot synthesis, solvent minimization, catalyst recovery, reaction efficiency, and energy requirements. Importantly, the overall sustainability of these systems depends not only on reaction-level performance but also on MOF synthesis, activation, material cost, solvent consumption, metal leaching, catalyst lifetime, and process-scale considerations. Accordingly, quantitative metrics such as process mass intensity, E-factor, reaction mass efficiency, energy consumption, techno-economic assessment, and life-cycle assessment are discussed as important tools for future evaluation. However, the overall sustainability of these systems depends not only on reaction performance but also on MOF synthesis, activation, solvent consumption, energy requirements, material cost, metal leaching, catalyst lifetime, resource utilization, sustainable manufacturing and end-of-life considerations.