Ugi reaction

The Ugi reaction is a first time from Ivar Ugi described multicomponent reaction of organic chemistry. In this reaction, a bis- amide results from the reaction of a ketone or aldehyde , an amine , an isonitrile and a carboxylic acid . The Ugi reaction is similar to the Passerini reaction (a three-component synthesis) of aldehydes or ketones with carboxylic acids and isonitriles, which was discovered 40 years earlier in Italy . The Ugi reaction is also often referred to as the Ugi four-component reaction.

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

In Combinatorial Chemistry the Ugi reaction is widely used in both high atom economy . A total synthesis for Crixivan includes the Ugi synthesis.

Reaction mechanism

The Ugi reaction begins with the condensation of the amine and the carbonyl compound to form imine 1 . The intermediate 2 is formed from 1 , the isocyanide and the carboxylic acid through nucleophilic addition . It has not yet been possible to show whether the trimolecular reaction proceeds in concert or in several stages. Shifting the acyl group gives the desired bis-amide 3 .

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

Review article

I. Ugi, S. Lohberger, R. Karl: The Passerini and Ugi Reactions . In: BM Trost, Ian Fleming, Clayton H. Heathcock (Eds.): Comprehensive Organic Synthesis . Vol. 2. Pergamon, Oxford 1991, ISBN 0-08-040593-2 , pp. 1083-1109 .
I. Ugi, B. Werner, A. Dömling: The Chemistry of Isocyanides, their MultiComponent Reactions and their Libraries . In: Molecules . tape 8 , no. 1 , January 31, 2003, p. 53–66 , doi : 10.3390 / 80100053 ( mdpi.org [PDF; 87 kB ]).
L. Banfi, R. Riva: The Passerini Reaction . Organic Reactions , Vol. 65, 2005, LE Overman Ed. Wiley, ISBN 0-471-68260-8 .

Individual evidence

^ Ivar Ugi: The α-Addition of Immonium Ions and Anions to Isonitriles Accompanied by Secondary Reactions . In: Angewandte Chemie International Edition in English . tape 1 , no. 1 , 1962, pp. 8-21 .
↑ Michael C. Pirrung, Koushik Das Sarma: Multicomponent Reactions Are Accelerated in Water . In: Journal of the American Chemical Society . tape 126 , no. 2 , January 2004, p. 444-445 , doi : 10.1021 / ja038583a .
↑ K. Rossen, PJ Pye, LM DiMichele, RP Volante, PJ Reider: An efficient asymmetric hydrogenation approach to the synthesis of the Crixivan® piperazine intermediate . In: Tetrahedron Letters . tape 39 , no. 38 , September 17, 1998, pp. 6823-6826 , doi : 10.1016 / S0040-4039 (98) 01484-1 .

[Ugi1962-1] Ivar Ugi: The α-Addition of Immonium Ions and Anions to Isonitriles Accompanied by Secondary Reactions . In: Angewandte Chemie International Edition in English . tape 1 , no. 1 , 1962, pp. 8-21 .

[Wasser2004-2] Michael C. Pirrung, Koushik Das Sarma: Multicomponent Reactions Are Accelerated in Water . In: Journal of the American Chemical Society . tape 126 , no. 2 , January 2004, p. 444-445 , doi : 10.1021 / ja038583a .

[Rossen1998-3] K. Rossen, PJ Pye, LM DiMichele, RP Volante, PJ Reider: An efficient asymmetric hydrogenation approach to the synthesis of the Crixivan® piperazine intermediate . In: Tetrahedron Letters . tape 39 , no. 38 , September 17, 1998, pp. 6823-6826 , doi : 10.1016 / S0040-4039 (98) 01484-1 .