Editorial: Isocyanide-Based Multicomponent Reactions

Abstract

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

Novel magnetic propylsulfonic acid-anchored isocyanurate-based periodic mesoporous organosilica (Iron oxide@PMO-ICS-PrSO3H) as a highly efficient and reusable nanoreactor for the sustainable synthesis of imidazopyrimidine derivatives

“…On the other hand, development of simple synthetic procedures for the synthesis of complex and diversityoriented organic molecules from readily available substrates is an important challenge in organic and medicinal chemistry. This can be achieved through multicomponent reactions (MCRs) strategy as a powerful process for the synthesis of molecules useful for pharmaceuticals, biological studies, secret communication and electronic including heterocyclic scaffolds [57][58][59][60][61][62] as well as fabrication of new task-specific materials such as drug delivery systems, nanocomposites, polymers, supramolecular systems and molecular machines [63][64][65][66][67][68] . In MCRs, three or more reactants simultaneously combine together in one reaction vessel to form a final product with high bond forming index such as imidazopyrimidine derivatives [69][70][71][72][73][74][75][76][77] .…”

Design, synthesis and biological evaluation of 1,5-disubstituted α-amino tetrazole derivatives as non-covalent inflammasome-caspase-1 complex inhibitors with potential application against immune and inflammatory disorders

“…Multicomponent reaction chemistry allows for the simultaneous introduction of several side chains via different building blocks which potentially can mimic P2–P4 sites. Multicomponent reactions we are experienced in are isocyanide-based MCRs [ 47 ]. Specifically, tetrazole yielding MCRs recently attracted considerable attention due to their scaffold diversity, ease of access and drug-like properties [ 48 ].…”

A trustworthy mechanochemical route to isocyanides

“…With such a breakthrough, isonitriles gained wide popularity in organic synthesis due to their extreme versatility [5][6][7]. Espe-cially, they are often used in heterocycles formation [8,9], multicomponent strategies [10,11], polymers production [12,13], and metal complexation [14,15]. The molecular structure is composed of an N-C planar triple bond where the nitrogen atom assumes a positive charge due to the fourth bond with a carbon chain, which could be aliphatic or aromatic.…”

“…With such a breakthrough, isonitriles gained wide popularity in organic synthesis due to their extreme versatility [ 5 – 7 ]. Especially, they are often used in heterocycles formation [ 8 – 9 ], multicomponent strategies [ 10 – 11 ], polymers production [ 12 – 13 ], and metal complexation [ 14 – 15 ].…”