Esters mixed Claisen condensation

Mixed Claisen condensations are analogous to mixed aldol condensations and involve carbon-carbon bond formation between the a carbon atom of one ester and the carbonyl carbon of another... 

The following equation shows an example of a mixed Claisen condensation m which a benzoate ester is used as the nonenohzable component... 

Give the structure of the product obtained when ethyl phenyl acetat C6H CH2C02CH2CH3) is treated with each of the following esters under conditions of the mixed Claisen condensation... 

In a reaction related to the mixed Claisen condensation nonenolizable esters are used as acylatmg agents for ketone enolates Ketones (via their enolates) are converted to p keto esters by reaction with diethyl carbonate... 

Mixed Claisen condensations (Section 21.3) Diethyl carbonate, diethyl oxalate, ethyl formate, and benzoate esters cannot form ester enolates but can act as acylating agents toward other ester enolates. 

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. 

Mixed Claisen-like reactions can also be carried out between an ester and a ketone, resulting in the synthesis of a jS-diketone. The reaction works best when the ester component has no a hydrogens and thus can t act as the nucleophilic donor. For example, ethyl formate gives high yields in mixed Claisen condensations with ketones. 

The Claisen reaction is a carbonyl condensation that occurs between two ester molecules and gives a /3-keto ester product. Mixed Claisen condensations... 

In a Claisen condensation the carbanion-enolate of an ester adds to the C=0 group of its parent ester. The addition is followed by loss of the OR group of the ester to give a -ketoester. In a mixed Claisen condensation the carbanion-enolate adds to the C=0 group of a molecule other than its parent. 

In these Claisen condensations OCjH, is displaced from the COOCjH, group by the a-carbanion formed from another ester molecule. Mixed Claisen condensations are feasible only if one of the esters has no a H. 

Claisen condensations can be carried out between two different esters but, because there are four possible products, mixtures often result. Less difficulty is encountered if one of the esters has no a hydrogen and reacts readily with a carbanion according to Equations 18-11 and 18-12. The reaction then has considerable resemblance to the mixed aldol additions discussed in Section 17-3C. Among the useful esters without a hydrogens, and with the requisite electrophilic reactivity, are those of benzenecarboxyiic, methanoic, ethanedioic, and carbonic acids. Several practical examples of mixed Claisen condensations are shown in Equations 18-14 through 18-16 (all of the products exist to the extent of 10% or so as the enol forms) ... 

Mixed Claisen condensations of two different esters can succeed if one component has no a hydrogens. 

Mixed Claisen condensations between a ketone and an ester with no a hydrogens are also successful. 

In the case of mixed Claisen condensations, a mixture of products is commonly avoided by using an acceptor ester that has no a-hydrogen. Examples of such reactants are ethyl formate... 

As with ketone enolate anions (see 16-34), the use of amide bases under kinetic control conditions (strong base with a weak conjugate acid, aprotic solvents, low temperatures), allows the mixed Claisen condensation to proceed. Self-condensation of the lithium enolate with the parent ester is a problem when LDA is used as a base, ° but this is minimized with LICA (lithium isopropylcyclohexyl amide).Note that solvent-free Claisen condensation reactions have been reported. ° ... 

The Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a /3-keto ester product. Mixed Claisen condensations between two different esters are successful only when one of the two partners has no acidic a hydrogens (ethyl benzoate and ethyl formate, for instance) and thus can function only as the acceptor partner. Intramolecular Claisen condensations, called Dieckmann cyclization reactions, provide excellent syntheses of five- and six-membered cyclic /3-keto esters starting from 1,6- and 1,7-diesters. 

Mixed Claisen condensations are feasible when one partner does not have acidic a-hydrogens, as in EtO-CHO (a formylating agent), PhC02Et, Et02CCO2Et, and (Et0)2C=0 (an ethoxycarbonylating agent). Eormate esters are the most reactive since they are part aldehyde. ... 

C.H. Heathcock and co-workers devised a highly convergent asymmetric total synthesis of (-)-secodaphniphylline, where the key step was a mixed Claisen condensation. In the final stage of the total synthesis, the two major fragments were coupled using the mixed Claisen condensation] the lithium enolate of (-)-methyl homosecodaphniphyllate was reacted with the 2,8-dioxabicyclo[3.2.1]octane acid chloride. The resulting crude mixture of (3-keto esters was subjected to the Krapcho decarboxylation procedure to afford the natural product in 43% yield for two steps. 

The use of preformed enolates continues to provide a valuable route for performing mixed Claisen condensations. Reaction of a 2-indolylacetic ester with 2 mol of LDA and treatment of the product with an a-trisubstituted acid chloride gave the corresponding keto ester as a diastereomeric mixture in 74% yield (equation 1) ... 

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