Lewis acid-catalyzed formation of Ugi four-component reaction product from Passerini three-component reaction system without an added amine

In the presence of a Lewis acid the phenol-Passerini three-component reaction (phenol-P-3CR) system is found to deliver a product of the phenol-Ugi four-component reaction (phenol-U-4CR). It is the first demonstration of an isocyanide as an amine equivalent in isocyanide-based multicomponent reactions (IMCRs). In general, by using Ti(O-i-Pr)4 in MeOH both phenol-U-4CR and U-4CR products are synthesized from an aromatic aldehyde, a phenolic or carboxylic acid, and an isocyanide. Moreover, by using MeCN as the solvent, the phenol-P-3CR products can be obtained in good yields without contamination of the phenol-U-4CR products.