The 8-component reaction

10 July 2009 - One-pot reactions

In multicomponent reactions several chemicals are brought together in a single reactor with formation of a single reaction product. Usually when you try this a complex mixture forms (A can react with B but also with C or D) requiring tedious separation. A successful multicomponent reaction therefore saves reaction steps, protecting/deprotecting and hence time and money. It also allows you to put together so-called chemical libraries really quickly. The current record holder, a 7-component reaction (7CR) has now been dethroned by an 8CR created by Elders/Orru et al. at the Vrije Universiteit Amsterdam (DOI).

The clever trick is that the 8CR is basically a tandem 3CR/3CR/4CR reaction with the first two also created by the Amsterdam group. The third one is a classic Ugi reaction. Imidazoline A is synthesised from a ketone , a primary amine and an alpha-acidic isocyano amide (DOI).


In B the starting amine is secondary (DOI) and with a lot of electron pushing the isonitrile group appears to be replaced by a nitrile.



In the second stage of the reaction A and B are combined with another amine and an aldehyde for the Ugi.


The final yield is modest and the reaction product a mixture of 4 diastereomers but the methodology nevertheless presents an intriguing starting point for library building. If only those isonitriles wouldn't smell so awful!.

Elders, N., van der Born, D., Hendrickx, L., Timmer, B., Krause, A., Janssen, E., de Kanter, F., Ruijter, E., & Orru, R. (2009). The Efficient One-Pot Reaction of up to Eight Components by the Union of Multicomponent Reactions Angewandte Chemie International Edition DOI: 10.1002/anie.200902683