Claisen ester condensation crossed

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). 

Key Mechanism 22-12 The Claisen Ester Condensation 1071 22-13 The Dieckmann Condensation A Claisen Cyclization 1074 22-14 Crossed Claisen Condensations 1074 22-15 Syntheses Using /3-Dicarbonyl Compounds 1077 22-16 The Malonic Ester Synthesis 1079 22-17 The Acetoacetic Ester Synthesis 1082 22-18 Conjugate Additions The Michael Reaction 1085 Mechanism 22-13 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

Crossed Claisen ester condensations between two different esters... 

We shall now give a few examples of crossed Claisen ester condensations between ordinary esters and the compounds we have just discussed. First, a reaction between a simple linear ester and diethyl oxalate performed under equilibrating conditions with ethoxide as the base. 

A crossed Claisen ester condensation between very enolizable ethyl phenylacetate and unenoliz-able but electrophilic diethyl carbonate works very well indeed under equilibrating conditions. 

It is exactly this protocol that resolved the lack of selectivity control in the crossed Claisen ester condensation of dissimilar esters, as is shown below for coupling of the esters of acetic and propionic acids ... 

Direct disconnection of compound C suggests a crossed Claisen ester condensation but, if we —.ove one methyl group first, a great simplification results as we can use a self-condensation. 

Second, methyl ester 61 is subjected to crossed ester condensation with methyl formate and triphenyl methyl sodium 64 as base.5,6 Ester 61 is deprotonated and the resulting anion 65 adds to methyl formate. The anion formed is stabilized by loss of methanolate yielding the desired product as its conjugated base. As a Claisen type ester condensation, all steps but the last are reversible since the resulting aldehydo ester 67 is more acidic than methanol therefore the last deprotonation step occurs irreversibly. The use of LDA19 as a base is also possible for this transformation. 

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... 

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