23.7 The Claisen Condensation Reaction Reaction of an ester having an  hydrogen with 1 equivalent of a base to yield a -keto ester

Mechanism of the Claisen Condensation Similar to aldol condensation: nucleophilic acyl substitution of an ester enolate ion on the carbonyl group of a second ester molecule

Features of the Claisen Condensation If the starting ester has more than one acidic a hydrogen, the product -keto ester has a doubly activated proton that can be abstracted by base Requires a full equivalent of base rather than a catalytic amount The deprotonation drives the reaction to the product

Worked Ex 23.3 What product would you obtain from Claisen condensation of ethyl propanoate?

Prob 23.11 Show the products you would expect to obtain by Claisen condensation of the following esters: (CH3)2CHCH2CO2Et Ethyl penylacetate Ethyl cyclohexylacetate

Prob 23.12 As shown in the mechanism, the Claisen rxn is reversible. That is, the β–keto ester can be cleaved by base into 2 fragments. Using curved arrows to indicate electron flow, show the mechanism by which this cleavage occurs.

23.8 Mixed Claisen Condensations Successful when one of the two esters acts as the electrophilic acceptor in reactions with other ester anions to give mixed -keto esters

Esters and Ketones Reactions between esters and ketones, resulting in -diketones Best when the ester component has no  hydrogens and can't act as the nucleophilic donor

Worked Ex 23.4 Diethyl oxalate (CO2Et) often gives high yields in mixed Claisen rxns. What product would you expect to obtain from a mixed Claisen rxn of ethyl acetate with diethyl oxalate?

Prob 23.13 What product would you expect from the following mixed Claisen-like reaction?

23.9 Intramolecular Claisen Condensations: The Dieckmann Cyclization Best with 1,6-diesters (product: 5-membered -ketoester) and 1,7-diesters (product: 6-membered -ketoester)

Mechanism of the Dieckmann Cyclization

Alkylation of Dieckmann Product The cyclic -keto ester can be further alkylated and decarboxylated as in the acetoacetic ester synthesis

Prob 23.14 What product would you expect from the following rxn: