15.30:
β-Dicarbonyl Compounds via Crossed Claisen Condensations
Claisen condensation between two different esters is termed crossed Claisen condensation.
If both esters contain α hydrogens, then four different types of ꞵ-ketoesters are formed. Of these, two are self-condensation products and the other two are crossed-condensation products.
A successful crossed Claisen condensation requires at least one ester molecule with no α hydrogen or the use of LDA base.
For instance, aryl esters have no α hydrogen and, therefore, cannot form enolates. They give crossed Claisen condensation products with other enolate-forming ester molecules.
Formate esters, in addition to containing no α hydrogen, are highly reactive compared to other esters, making them suitable for crossed Claisen condensation.
If a less reactive, no α-hydrogen-containing ester is used, an excess of it is required for a feasible reaction.
If α-hydrogen-containing esters are used, then a strong base like LDA facilitates a directed crossed Claisen condensation by generating an irreversible ester enolate, followed by its reaction with another ester molecule.
15.30:
β-Dicarbonyl Compounds via Crossed Claisen Condensations
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.
