Wednesday, January 18, 2006

ChemRefer answers Ugi phenol question

I contacted ChemRefer about their unsatisfactory answer concerning the problem of phenols in a Ugi synthesis and they promptly came back to me with a beauty:

Phenol Ugi-Smiles Systems: Strategies for the Multicomponent N-Arylation of Primary Amines with Isocyanides, Aldehydes, and Phenols
Laurent El Kaïm, Dr. *, Laurence Grimaud, Dr. *, Julie Oble
Volume 44, Issue 48 , Pages 7961 - 7964 Published Online: 15 Nov 2005

It turns out that phenols can react like acids in a Ugi reactions but their reactivity is dependent upon electron-withdrawing groups on the aromatic ring. In the case of our target aldehyde, our phenolic system is a catechol so I would not expect the reaction with the phenol to be fast compared to the carboxylic acid. However, one difference in our case is that the phenol would be attacking intramolecularly, though I have not yet made the model to see if the meta position of the phenol group can even reach to cyclize.

I would still ask everyone in our group to continue reading up on the Ugi reaction and post if you find anything relevant. But my overall impression after reading this article is that there is enough of a chance for the unprotected aldehyde to work that we should give it a shot.

By the way this article also points out that aldehydes are much more reactive than ketones so we may also be able to get away with unprotected ketones in our starting materials.


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