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

Abstract

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.

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

“…The Ugi-type multicomponent reactions between imines, carboxylic acids, and isocyanides, and Mannich-type reactions between iminium and carbonyl groups have found many applications in organic synthesis [108]. Che's group employed the methodology of oxidation of an amine with singlet oxygen to produce an imine, which was used as a substrate in the Ugi-type reaction.…”

Novel Methodologies for Chemical Activation in Organic Synthesis under Solvent-Free Reaction Conditions

“…Multicomponent reactions reflect also the state of the art in chemical control since generally C-C and C-X (X = heteroatom) bonds are formed in one single step. For recent interesting applications of mechanochemistry in multicomponent reactions see references [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ].…”

One‐Pot Construction of Bis‐Heterocycles through Isocyanide Based Multicomponent Reactions

“…[17a,29] The commonly accepted pathway for U-4CR is shown in Scheme 1A, which follows i) formation of an imine from the rapid reaction of aldehyde and amine, ii) carboxylic acid-driven protonation of imine iii) Simultaneous nucleophilic attack of isocyanide on iminium cation and carboxylate anion on isocyanide, and iv) finally, intramolecular acyl group shift (Mumm rearrangement) to yield U-4CR product. [30] Transformation of an energetic isocyanide carbon into the stable amide carbonyl carbon atom is the main driving force for this reaction to occur under mild conditions. The reaction is highly atom-efficient since the entire process that generates four chemical bonds involves the elimination of only one water molecule.…”

“…For further readings on Ugi -MCRs, the reader is directed towards more comprehensive reviews. [30][31][32]…”