Crossed Claisen reactions

Crossed Claisen reactions with two different esters, each of which has a-H atoms, are seldom useful synthetically as there are, of course, four possible products. Crossed Claisen reactions are, however, often useful when one of the two esters has no a-H atoms, e.g. HCOzEt, ArC02Et, (C02Et)2, etc., as this can act only as a carbanion acceptor. Such species are in fact good acceptors, and the side reaction of the self-condensation of the other, e.g. RCH2C02Et, ester is not normally a problem. Intramolecular Claisen reactions, where both C02Et groups are part of the same molecule [e.g. (123)], are referred to as Dieckmann cyclisations. These work best, under simple conditions, for the formation of the anions of 5-, 6- or 7-membered cyclic / -ketoesters... 

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

For die same reason it is generally not feasible to cany out a crossed-Claisen reaction between die enolate of one ester and a second ester which has a protons. This is due to the fact diat if nucleophilic addition to die carbonyl group is not fast, proton exchange can occur, giving a mixture of etiolates and thus a mixture... 

A Claisen reaction between two different carbonyl compounds is called a crossed Claisen reaction. 

A crossed Claisen reaction is synthetically useful in two different instances. 

When one ester has no a hydrogens, a crossed Claisen reaction often leads to one product. Common esters with no a H atoms include ethyl formate (HC02Et) and ethyl benzoate (CjH5C02Et). For example, the reaction of ethyl benzoate (as the electrophile) with ethyl acetate (which forms the enolate) in the presence of base forms predominately one p-keto ester. 

The reaction of a ketone and an ester in the presence of base also forms the product of a crossed Claisen reaction. The enolate is always formed from the ketone component, and the reaction works best when the ester has no a hydrogens. The product of this crossed Claisen reaction is a P-dicarbonyl compound, but not a p-keto ester. 

B Other Useful Variations of the Crossed Claisen Reaction... 

What four compounds are formed from the crossed Claisen reaction of CH3CH2CH2CH2C02Et and CH3CH2C02Et ... 

What starting materials are needed to synthesize each compound by a crossed Claisen reaction ... 

Crossed Claisen reaction to form a p-dicarbonyl compound... 

Crossed Claisen reaction (Section 24.6) A Claisen reaction in which the two reacting esters are different. 

For a method of allowing certain crossed-Claisen reactions to proceed with good yields, see Tanabe, Y. Bull. Chem. Soc. Jpn. 1989, 62, 1917. 

Using LDA allows one to direct crossed aldol and crossed Claisen reactions. For example, consider how to perform the following reaction. 

Crossed Claisen reactions can be used to give high yields of a desired product from two different esters if one ester has no a-hydrogens (cannot form an enolate anion) and is used in excess. 

Avobenzone is a conjugated compound that absorbs ultraviolet light with wavelengths in the 320-400 nm region, so it is a common ingredient in commercial sunscreens. Write out two different crossed Claisen reactions that form avobenzone. 

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. ... 

A titanium catalyst is used to control a crossed Claisen reaction in the Tanabe synthesis (Eq. 8.41) [58]. 

In a crossed Claisen reaction between an ester and a ketone, the enolate is formed from the ketone, and the product is a P-dicarbonyl compound. 

A P-dicarbonyl compound like avobenzone is prepared by a crossed Claisen reaction between a ketone and an ester. 

Crossed Claisen reactions can be achieved when one component cannot be enolized— confusingly, this name is used whether the nucleophilic component is an ester or a ketone (Figure 17.35). The product of the reaction in the second example was used in a morphine synthesis and is isolated in the enol form shown. 

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