Ugi Reaction

The Ugi four-component condensation (U-4CC) between an aldehyde, an amine, a carboxylic acid and an isocyanide allows the rapid preparation of α-aminoacyl amide derivatives. The Ugi Reaction products can exemplify a wide variety of substitution patterns, and constitute peptidomimetics that have potential pharmaceutical applications. This reaction is thus very important for generating compound libraries for screening purposes.

---

Mechanism of the Ugi Reaction

The mechanism is believed to involve a prior formation of an imine by condensation of the amine with the aldehyde, followed by addition of the carboxylic acid oxygen and the imino carbon across the isocyanide carbon; the resulting acylated isoamide rearranges by acyl transfer to generate the final product.

Recent Literature

Phenol Ugi-Smiles Systems: Strategies for the Multicomponent N-Arylation of Primary Amines with Isocyanides, Aldehydes, and Phenols
L. El Kaim, L. Grimaud, J. Oble, Angew. Chem. Int. Ed., 2005, 44, 7961-7964.

Acid-Free, Aminoborane-Mediated Ugi-Type Reaction Leading to General Utilization of Secondary Amines
Y. Tanaka, T. Hasui, M. Suginome, Org. Lett., 2007, 9, 4407-4410.

2-Bromo-6-isocyanopyridine as a Universal Convertible Isocyanide for Multicomponent Chemistry
G. van der Heiden, J. A. W. Jong, E. Ruijter, R. V. A. Orru, Org. Lett., 2016, 18, 984-987.

Use of a Design of Experiments approach for the optimisation of a microwave assisted Ugi reaction
H. Tye, M. Whittaker, Org. Biomol. Chem., 2004, 2, 813-815.

A straightforward approach towards thiazoles and endothiopeptides via Ugi reaction
U. Kazmaier, S. Ackermann, Org. Biomol. Chem., 2005, 3, 3184-3187.

A Modified U-4CR Reaction with 2-Nitrobenzylamine as an Ammonia Equivalent
K. Sung, F.-L. Chen, P.-C. Huang, Synlett, 2006, 2667-2669.

Facile Construction of Hydantoin Scaffolds via a Post-Ugi Cascade Reaction
Z.-G. Xu, Y. Ding, J.-P. Meng, D.-Y. Tang, Y. Li, J. Lei, C. Xu, Z.-Z. Chen, Synlett, 2018, 29, 2199-2202.