Brønsted acidity of substrates influences the outcome of passerini three-component reactions.

Passerini three-component reactions of aldehydes, isocyanides, and strong carboxylic acids (i.e., pK(a) < 2) yield alpha-acyloxycarboxamides and/or alpha-acylaminocarboxamides, the characteristic products of Ugi four-component reactions. We propose that alpha-acylaminocarboxamide formation with these substrates is a consequence of in situ Brønsted acid-catalyzed reaction of the isocyanide and aldehyde to yield an imine that participates in an Ugi-type reaction. The apparent transfer of the isocyanide alpha-carbon to protic solvents as a formyl group during imine formation is indicative of new isocyanide reactivity.