Editorial on the Research Topic
Isocyanide-Based Multicomponent ReactionsMulticomponent reactions are an inspiring class of transformations in organic chemistry (Zarganes-Tzitzikas et al., 2015). These reactions, which incorporate three or more reactants into a single reaction product, offer advantages over traditional bimolecular reactions. Multicomponent reactions accelerate exploration of chemical space by reducing the number of synthetic and purification operations required to make a given target. The accompanying atom economy of multicomponent reactions further improve the sustainability of the chemical enterprise. The mechanisms of multicomponent reactions also challenge our understanding of subtle reactivity principles. Besides green chemistry attributes and mechanistic beauty, a key feature of multicomponent reactions that has not yet been fully embraced is the easy engineering of functional materials (Afshari and Shaabani, 2018). Functions can range from affinity ligands for immunoglobulin purification (Kruljec and Bratkovič, 2017) to imaging compounds in biological systems (Lin et al., 2017) to proteome-wide mapping of protein-protein interactions (Kambe et al., 2014) to molecular machines (García-González et al., 2018) to molecular keys for applications in advanced encryption standard cryptography with molecular steganography (Boukis et al., 2018). According to the basic principle form follows function, forms can be assembled in a unique fashion via multicomponent reactions from building blocks connected to certain properties. Such properties can be chirality, ligands for metals, fluorescence, extended π-systems with tunable HOMO-LUMO distances, or hydrogen bond donor-acceptor configurations. An emerging and rapidly growing field in this respect is the use of multicomponent reactions in polymer science and engineering (Llevot et al., 2017).Among the most well-known and diverse class of multicomponent reactions are those in which an isocyanide (a.k.a., isonitrile) reagent is incorporated in the product. Isocyanide-based multicomponent reactions were some of the very first multicomponent reactions discovered in organic chemistry. Mario Passerini reported the reaction of an aryl isocyanide with ketones and carboxylic acids, the first isocyanide-based three-component reaction, nearly a century ago (Passerini, 1921). Ivar Ugi disclosed the first isocyanide-based four component reaction almost 40 years later (Ugi and Steinbrückner, 1960). Ugi's insights about the mechanisms of these multicomponent reactions have stimulated discoveries of numerous reaction variants. Ugi also recognized the potential for multicomponent reactions to enable combinatorial library synthesis and to serve as platforms for diversity-oriented synthesis. These pillars have sustained more than a half century of research into isocyanide-based multicomponent reactions. As we reflect upon the state-of-the-art in the field, these themes remain pervasive as synthetic organic chemists apply