Sustainable Synthetic Routes for the Construction of Functionalized Heterocyclic Scaffolds

The preparation of functionalized heterocyclic structures using sustainable approaches has gained great importance within contemporary synthetic organic chemistry. This review focuses on recent progress in sustainable synthetic approaches to obtain various heterocycles, paying special attention to microwave-assisted chemistry, ultrasound, electroactivation, photoredox catalysis, mechanochemistry, and biocatalysis. It is evident from the discussed literature that non-classical activation approaches invariably exceed traditional thermal activation in terms of reaction times, energy and waste production. Quantitative green parameters such as atom economy, E-factors, process mass intensity, and reaction mass efficiency prove that solvent-free or aqueous medium-based multicomponent reactions provide the most sustainable synthetic approach. The employment of heterogeneous catalysts, including magnetic nanoparticles and ionic liquids, contributes to greater recyclability and lower impact on the environment. Comparing microwave-assisted procedures with other approaches, it becomes clear that these processes significantly decrease reaction times from hours to minutes while maintaining high yields. Electrochemical and photochemical approaches, on the contrary, provide unique selectivity that cannot be achieved using thermal activation. Sustainable synthetic approaches should further develop in terms of process intensification, flow chemistry, and predictive green metrics.