A multicomponent reaction towards N-(Cyanomethyl)amides

Multicomponent reactions (MCRs)[1] have emerged as useful tools in diversity-oriented synthesis (DOS).[2] Although a number of substituents can be varied over a broad range, MCRs often access products of one specific scaffold, limiting the overall chemical diversity. To overcome this, MCRs have been combined with other types of reactions such as Diels–Alder reactions,[3] click chemistry,[4] and cyclization strategies[5] to generate structural diversity and a high degree of complexity in a minimal number of reaction steps. Our group contributed in this field by trapping 1-azadienes,[ 6] generated by the three-component reaction (3-CR) between phosphonates, nitriles and aldehydes,[7] with various reactants resulting in novel 4-CRs for a variety of heterocyclic scaffolds.[8]