Many published reviews summarize the Ugi 4CR from different viewpoints, but the aim of the presented review on Ugi 4CR together with Passerini three-component reaction (Passerini 3CR) is to introduce a successful mode for the study on MCRs, in which the research on a MCR may involve four aspects including mechanism, substrate, catalyst, and application. The quantum calculation on the energy variation of Ugi 4CR reveals that the addition of isocyanide to imine controls the reaction rate of Ugi 4CR, and imine is generated via the reaction between the amine and ketone at the first step in Ugi 4CR. As a result, the investigation on the substrates of Ugi 4CR focuses on the formation of imine and the resources of carboxylic acid and ketone. Moreover, some catalysts are employed to induce the diastereoisomer ratio because a chiral center is involved in the product of Ugi 4CR. In addition, Lewis acid is used to activate the inert reagents or to drive the further reactions based on Ugi 4CR products.
The application of Ugi 4CR is not the major concern in this review because many previous reviews have focused on this topic. Only some recently published results are documented herein. For example, Ugi 4CR can be used to construct macromolecules with complicated topological structure, to introduce medicinal molecule into nanoparticles, and to synthesize biological-related molecules. Finally, a successful model for the research on MCR can be summarized from the study on Ugi 4CR. Understanding mechanism is the basis for investigating MCR, followed by expanding the suitable substrates and exploring the chiral catalysts. As a result, the MCR can be widely applied to synthesize various molecules.