This three-component reaction between a carboxylic acid, a carbonyl compound such as a ketone or aldehyde, and an isocyanide, offers direct access to α-hydroxy carboxamides.
Mechanism of the Passerini Reaction
The Passerini Reaction proceeds rapidly if the reaction is performed in aprotic solvents at room temperature. High yields are obtained with high concentrations of the starting materials in the reaction mixture.
From these findings, it is assumed that the Passerini Reaction does not follow an ionic pathway. Hydrogen bonding is believed to play a crucial role in the formation of the presumed cyclic transition state for this reaction.
Passerini three-component reaction under catalytic aerobic conditions allows the conversion of alcohols instead of aldehydes. The reaction of alcohols, isocyanides, and carboxylic acids in toluene in the presence of a catalytic amount of cupric chloride, NaNO2, and TEMPO afforded, under an oxygen atmosphere, the P-3CR adducts in good yields.
J. Brioche, G. Masson, J. Zhu, Org. Lett., 2010, 12, 1432-1435.
A new method for a highly effective addition of isocyanides to aldehydes proceeded smoothly in the presence of a silanol to give the corresponding α-siloxyamides in high yields. A wide range of aldehydes and isocyanides are applicable in this reaction.
T. Soeta, Y. Kojima, Y. Ukaji, K. Inomata, Org. Lett., 2010, 12, 4280-4283.
A three-component addition of isocyanides to phenol derivatives and aldehydes in methanol forms O-arylated compounds in a new Passerini-type reaction. The key step is an irreversible Smiles rearrangement of intermediate phenoxyimidate adducts.
L. El Kaim, M. Gizolme, L. Grimaud, Org. Lett., 2006, 8, 5021-5023.