Functionalized Silica-Catalyzed Multicomponent Reactions for Sustainable Heterocycle Synthesis: Structure–Activity Relationships, Mechanistic Insights, Green Metrics, and Future Perspectives

Catalysis has been recognized as a key science in contemporary chemistry, owing to the significant potential of nanocatalysts and organic–inorganic hybrid materials, due to their high surface area and tunability properties, as well as the possibility of conducting green syntheses. Multicomponent reactions (MCRs) constitute an efficient one-pot sustainable manufacturing approach for the synthesis of a variety of heterocycles in reduced number of steps, reagents and hazardous waste. Si-based hybrid nanocatalysts and functionalized silica materials have been shown to be effective catalysts with a high catalytic activity, selectivity, and recyclability, whose mechanisms have been studied extensively and related to substrate activation and reaction acceleration. In this review, recent developments in heterogeneous Si-based hybrid nanocatalysts and functionalized silica supported materials for the MCR preparation of pyridines, pyrimidines, imidazoles, quinolines, quinoxalines, thiazoles, chromenes, pyrans, and pyrazoles are highlighted. The review particularly focuses on acid/base-functionalized silica, immobilized metals, ionic-liquid/silica hybrids, magnetic silica, and hierarchical silica. The mechanisms of these catalysts are also considered in this work, particularly substrate activation, acid–base cooperation, and adsorption and stabilization of the reactive intermediates. Sustainable catalysis strategies include ones that are solvent-free and ones that use water as a solvent, catalyst recovery and recycling, energy-efficient processes, and strategies that have a high atom economy and reaction mass efficiency and low E-factor. These advances illustrate the feasibility of functionalized silica-based MCRs as environmentally friendly materials for heterocycle production.