Review on the Ugi Multicomponent Reaction Mechanism and the Use of Fluorescent Derivatives as Functional Chromophores

In the present mini-review we discuss the findings, controversies, and gaps observed for the Ugi four-component reaction. The Ugi multicomponent reaction, performed by mixing an aldehyde, an amine, a carboxylic acid, and an isocyanide, is among the most important isocyanide-based multicomponent reactions (MCRs), allowing multiple bond formations (C-C and C-N) in a single synthetic step. The possibility of two reaction pathways and the little understood solvent effect over this transformation renders this reaction as one of the hardest challenges to overcome. The little knowledge of the mechanism of the Ugi MCR hinders the development of new and efficient chiral catalytic systems to further the application of the derivatives obtained by enantioselective versions. The asymmetric transformation is in this context a bigger challenge, and little is known about the mechanism of these few available versions. The new trend of functional chromophore synthesis by MCRs is also highlighted, and the few examples already disclosed in the literature exemplify the huge opportunity for investigation and creative ideas using the Ugi four-component reaction.