Crossed Claisen condensations are base-promoted reactions between two different ester molecules producing β-dicarbonyl compounds. The reaction involving esters, with both containing α hydrogen, results in a mixture of four different products that are difficult to isolate. This reduces the synthetic utility of the reaction.

This problem is resolved by using one of the esters without any α hydrogen, such as aryl esters.

Additionally, highly reactive molecules like formate esters serve as effective electrophilic partners in cross Claisen condensation.

Similarly, less reactive esters with no α protons make the reaction feasible when present in excess quantity.

Another approach to obtain an efficient cross Claisen condensation is the use of a strong, sterically hindered base—LDA. It irreversibly deprotonates one of the esters to enolate, while the other ester acts as an electrophile.

A variation of crossed Claisen condensation is the reaction of ketones with esters, wherein the enolate of ketone attacks the carbonyl center of the ester producing ꞵ-dicarbonyl compounds.