Mixed Claisen reaction

The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones (Section 23.5). Mixed Claisen reactions are successful only when one of the two ester components has no a hydrogens and thus can t form an enolate ion. For example, ethyl benzoate and ethyl formate can t form enolate ions and thus can t serve as donors. They can, however, act as the electrophilic acceptor components in reactions with other ester anions to give mixed /3-keto ester products. 

Diethyl oxalate, (CCqEt, often gives high yields in mixed Claisen reactions. What product would you expect to obtain from a mixed Claisen reaction of ethyl acetate with diethyl oxalate ... 

Strategy A mixed Claisen reaction is effective when only one of the two partners has an acidic cy hydrogen atom. In the present case, ethyl acetate can be converted into its enolate ion, but cliethyl oxalate cannot. Thus, ethyl acetate acts as the donor and diethyl oxalate as the acceptor. 

In the mixed Claisen reaction of cyclopentanone with ethyl formate, a much higher yield of the desired product is obtained by first mixing the two carbonyl components and then adding base, rather than by first mixing base with cyclopentanone and then adding ethyl formate. Explain. 

To be synthetically useful, a mixed Claisen reaction (crossed Claisen reaction) needs one ester with no a-hydrogens, so that it cannot become... 

Cleavage of P-diketones, the products of a mixed Claisen reaction between an ester electrophile and a ketone nucleophile (see Box 10.13), behave similarly towards base, and a reverse Claisen reac-... 

As shown in Worked Example 23.4, dimethyl oxalate is a very effective reagent in mixed Claisen reactions. 

Practice ProWem 25.4 DieOyfl oxalato, (C02Et)., can give high yields in mixed Claisen reactions... 

Since the disconnection in the example above leads to two identical pieces, this results in a simple synthesis and an ideal retrosynthesis (the more nearly equal the resulting pieces, the better the disconnection). The regioselectivity of a mixed Claisen reaction can be controlled in a stepwise synthesis that employs LDA, as done in a mixed aldol reaction. 

In Summary Claisen condensations are endothermic and therefore would not take place without a stoichiometric amount of base strong enough to deprotonate the resulting 3-ketoester. Mixed Claisen condensations between two esters are nonselective, unless they are intramolecular (Dieckmann condensation) or one of the components is devoid of a-hydrogens. Ketones also participate in selective mixed Claisen reactions because they are more acidic than esters. 

Write the structure of the product of a mixed Claisen reaction using ethyl propanoate and diethyl carbonate. 

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