Claisen reaction mixed/crossed

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

However, if one of the ester partners has enolizable a-hydrogens and the other does not (e.g., aromatic esters or carbonates), the mixed reaction (or crossed Claisen) can be synthetically useful. If ketones or nitriles are used as the donor in this condensation reaction, a P-diketone or a p-ketonitrile is obtained, respectively. 

Reaction between Two Different Aldehydes. In the most general case, this will produce a mixture of four products (eight, if the alkenes are counted). However, if one aldehyde does not have an a hydrogen, only two aldols are possible, and in many cases the crossed product is the main one. The crossed-aldol reaction is often called the Claisen-Schmidt reaction. The crossed aldol is readily accomplished using amide bases in aprotic solvent. The first aldehyde is treated with LDA in THF at —78°C, for example, to form the enolate anion. Subsequent treatment with a second aldehyde leads to the mixed aldol product. The crossed aldol of two aldehydes has been done using potassium ferf-butoxide and Ti(OBu)4. ... 

When carboxylic esters containing an a hydrogen are treated with a strong base, such as sodium ethoxide, a condensation occurs to give a p-keto ester via an ester enolate anion. ° This reaction is called the Claisen condensation. When it is carried out with a mixture of two different esters, each of which possesses an a hydrogen (this reaction is called a mixed Claisen or a crossed Claisen condensation), a mixture of all four products is generally obtained and the reaction is seldom useful synthetically. However, if only one of the esters has an... 

This methodology was also applied to the crossed Claisen reaction between carboxylic acids and methyl hexanoate. The carboxylic acids are initially converted to mixed anhydrides by reacting their in situ formed sodium carboxylates with chlorofor-mates these intermediates then react with NMI as shown previously to form electrophilic acyl ammonium species (eq 46). This strategy was applied to the synthesis of natural perfumes such as (/ )-muscone and cw-jasmone. ... 

When a mixture of two dissimilar esters (R -CH2 C02Et and R2-CH2 C02Et) is treated with sodium as the ethoxide, a mixed / -keto ester (R -CH2 C0 CH(R2)-C02Et or R2-CH2 CH(R1) C02Et) may be formed. However the disadvantage which is common to all mixed reactions, i.e. the formation of both symmetrical and crossed products, reduces its preparative value. Exceptions are provided in those cases where one of the esters contains no a-hydrogens. An important example is provided by the use of esters of oxalic acid in such mixed Claisen ester condensations (e.g. Section 5.14.3, p. 735, and Expt 8.37). 

Crossed Claisen condensations can be chemoselective even when the nonenolizable ester is not a better electrophile than the enolizable ester. This can be accomplished by a suitable choice of reaction conditions. The nonenolizable ester is mixed with the base and the enoliz-able ester is added slowly to that mixture. The enolate of the enolizable ester then reacts mostly with the nonenolizable ester for statistical reasons it reacts much less with the noneno-lized form of the enolizable ester, which is present only in rather small concentration. Carbonic acid esters and benzoic acid esters are nonenolizable esters of the kind just described. 

The reaction described for ethyl butanoate is a self-condensation, but as with the aldol condensation, Claisen condensation of two different esters can result in a mixture of products under thermodynamic control conditions. The reaction of two different esters is called the crossed-Claisen (or a mixed Claisen) condensation. A generalized reaction involving RC02Et and RlC02Et can lead to at least four different condensation... 

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