Claisen and Dieckmann Condensations

Acylation of Carboxylic Esters by Carboxylic Esters. The Claisen and Dieckmann Condensations Alkoxycarbonylalkyl-de-alkoxy-substitution... 

The Claisen and Dieckmann condensations are reactions in which an ester enolate acts as a nucleophile toward an ester. The Dieckmann condensation is simply the intramolecular variant of the Claisen condensation. In these reactions, the alkoxy part of the ester is substituted with an enolate to give a jS-ketoester. A stoichiometric amount of base is required for this reaction, because the product is a very good acid, and it quenches the base catalyst. In fact, this quenching reaction is what drives the overall reaction to completion. The Claisen condensation is especially useful when one of the esters is nonenolizable (e.g., diethyl oxalate, ethyl formate, or diethyl carbonate). 

The 3-keto esters formed in the Claisen and Dieckmann condensations can act as synthons for a variety of groups. If the a-carbon bears a proton then this is acidic and can be replaced by another electrophile. Alkylation and acylation are important synthetic reactions and can be carried out sequentially or, since the cyclizing reactions are basic, consecutively in one pot. Examples are illustrated in Scheme 31. 

Addition of enolate anions derived from aldehydes or ketones (aldol reactions) and esters (Claisen and Dieckmann condensations) to the carbonyl groups of other aldehydes, ketones, or esters. 

Recall from Section 18.4C that hydrolysis of an ester in aqueous sodium hydroxide (saponification) followed by acidification of the reaction mixture with aqueous HCl converts an ester to a carboxylic acid. Also recall from Section 17.9 that j8-ketoacids and j8-dicarboxylic adds (substituted malonic acids) readily undergo decarboxylation (lose CO2) when heated. Both the Claisen and Dieckmann condensations yield esters of j8-ketoacids. The following equations illustrate the results of a Claisen condensation followed by hydrolysis of the ester, acidification, and decarboxylation. 

Note that aldol, Claisen, and Dieckmann condensations all give primary products with oxygens in a 1,3 relationship. The Michael reaction with enolate anions gives products with oxygens in a 1,5 relationship. These relationships are a consequence of the polarization of the reagents. In aldol, Claisen, and Dieckmann condensations, the carbonyl carbon is positive and the a-position is negative. 

The product of Claisen and Dieckmann condensation reactions can be treated with aqueous base (saponification) followed by acidification to convert the j8-ketoester group into a )8-ketoacid that is then heated to cause decarboxylation to give a ketone product and CO2. 

The Ti- and Zr- Claisen and Dieckmann condensations exhibit powerful reactivity to realize C-C bond formations between various carboxylic esters under mild reaction conditions. This characteristic merit would promise a large ring closing with higher concentrations and speed. 

Claisen and Dieckmann condensations are reversible. The driving force is the deprotonation of the alpha hydrogen in the product between the two carbonyls. This deprotonation prevents the reaction from reversing, pulling the product out of the equilbrium. 

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