Ugi reaction

The Ugi reaction is a multi-component reaction was first described by Ugi, Ivar of organic chemistry in which a ketone or an aldehyde, an amine, an isonitrile, and a carboxylic acid bis- amide form a. The Ugi reaction is similar to the already 40 years previously discovered in Italy Passerini reaction ( a three-component synthesis) of aldehydes or ketones with carboxylic acids and isonitriles. Often, the Ugi reaction is also called Ugi four component reaction.

The Ugi reaction is exothermic, typically the reaction is complete a few minutes after the addition of the isonitrile. High concentrations ( 0.5 to 2.0 M) of the reactants resulting in the highest yields. Polar aprotic solvents such as DMF have been proven so far. However, there is also evidence of good results in water.

In combinatorial chemistry, the Ugi reaction is widely used in both high atom economy. A total synthesis of Crixivan involves the Ugi synthesis.

Reaction mechanism

The Ugi reaction starts with the reaction between the carbonyl compound and the amine to the imine 1 condensation of the imine with the isocyanide and the carboxylic acid gives intermediate 2 It is not yet possible to show whether the trimolecular reaction concerted or in several stages. Shift of the acyl group gives the desired bis- amide 3

It has been shown that the yield can be increased by previously isolating the imine 1. This variant of the Ugi reaction is a three-component synthesis.