title: Isocyanide-Based Multicomponent Reactions for the Synthesis of Heterocycles.
abstract: Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and bioconjugation. Traditional isocyanide-based MCRs utilize an external nucleophile attacking the reactive nitrilium ion, the key intermediate formed in the reaction of the imine and the isocyanide. However, when reactants with multiple nucleophilic groups (bisfunctional reactants) are used in the MCR, the nitrilium intermediate can be trapped by an intramolecular nucleophilic attack to form various heterocycles. The implications of nitrilium trapping along with widely applied conventional isocyanide-based MCRs in drug design are discussed in this review.
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. varadia@mskcc.org.
authors.forename: András
authors.initials: A
authors.lastname: Váradi
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. palmertr@grinnell.edu.
authors.forename: Travis C
authors.initials: TC
authors.lastname: Palmer
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. rebecca.dardashti@mail.huji.ac.il.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Notis Dardashti
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. majumdas@mskcc.org.
authors.forename: Susruta
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003486:Cyanides / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D003486:Cyanides; D006571:Heterocyclic Compounds; D007097:Imines
keywords: Ugi reaction; heterocycles; nitrilium trapping