Sustainable Synthesis of Pseudopeptides via Isocyanide-Based Multicomponent Reactions in Water

The impressive success in the synthesis of novel products via sustainable and green methods is a crucial purpose in organic synthesis. Water as a "green solvent"plays a vital role in accelerating some organic reactions, displaying unique reactivity and selectivity from conventional organic solvents. The isocyanide-based multicomponent reactions (I-MCRs) as sustainable and versatile reactions have received significant consideration in the synthesis of pseudopeptidic frames, especially in drug discovery. This is because of the unique nature of isocyanides that play as a special active reactant. I-MCRs in water as a solvent and reagent for the synthesis of pseudopeptidic compounds have become an interesting research direction, enabling simultaneous growth of both I-MCRs and green solvents toward ideal organic synthesis. The reaction rate of I-MCRs was accelerated in water as a solvent due to the lower activation volumes and condensation of several reactants into a single reactive intermediate and product. Furthermore, I-MCRs executed possibly in water are mild, easily controlled, and environmentally friendly, which conform well to "Green Chemistry"principles. On the other hand, these powerful organic syntheses in water and aqueous media are perpetuated by acceleration and reduction in the number of workups, purification, and extraction steps. The main subject of this review is I-MCRs that are performed in the water toward the sustainable synthesis of pseudopeptide structures. It deserves to be pointed out that whereas significant progress has been recently made on the MCRs in water and aqueous media for organic transformations, there is no exclusive account to focus on and publish about the eco-friendly I-MCRs for pseudopeptides. Nevertheless, we hope this themed assemblage will be attractive and useful for organic and pharmaceutical chemists and encourage more reaction development in this fascinating engaging field. © 2022 American Chemical Society.