Friday, June 09, 2006

Variation of the Claisen Condensation

Researchers at Kwansei Gakuin University developed a better way of synthesizing β-keto esters from esters and acid chlorides as well as from esters and carboxylic acids. It is based on the Ti-self-Claisen condensation performed in a previous study. The new method is a Ti-crossed-Claisen condensation with a high yield of the desired product and a low yield of the undesired self-condensed reaction. In the previous study, the catalyst used was TiCl4-Bu3N. In this study, a co-catalyst, N-methylimidazole, was used to prevent self-condensing in the ester/acid chloride reaction. During the reaction, the acid chloride condenses with the N-methylimidazole to form an electrophilic acylammonium intermediate. An example of the reaction is shown below:

In the reactions between esters and carboxylic acids, the researchers developed a new procedure using mixed anhydrides to react with the ester and create an intermediate. The mixed anhyrides are formed in situ between sodium carboxylates and Cl3CCOCl. An example is shown below:


In order to show that these new methods are easier and work better than previous procedures, the researchers synthesized cis-Jasmone and (R)-Muscone. The resulting yields were 46% and 53% respectively. This reaction is a useful new method particularly because products of Ti-crossed-Claisen condensation reactions are useful reagents for organic syntheses, especially those that involve asymmetric transformations.

More information is available here.