Passerini's reaction
Isonitriles and multicomponent reactions

The reaction involving a carboxylic acid, a carbonyl compound and an isonitrile to lead to the formation of an α-acyloxycarboxamide was discovered in 1921 by Mario Passerini (figure 12) [18] [19]. It is the first multicomponent reaction involving isonitriles [20].

The mechanism of this reaction has given rise to much discussion [21] and is still subject to controversy [22] [23] [24] [25] [26] [27]. One important observation is that the Passerini reaction is accelerated in low-polar aprotic solvents (CH₂Cl₂, Et₂O, AcOEt, THF), which is not in agreement with a three-step ionic mechanism including protonation of the carbonyl, formation of the nitrilium...