15.29:
Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization
Diesters undergo intramolecular Claisen condensation to produce cyclic β-ketoesters. This process is called Dieckmann cyclization and requires one equivalent of a strong base to push the reaction to completion.
1,6- and 1,7-diesters are the preferred substrates for cyclization as they produce stable five- and six-membered rings, respectively.
In the diester substrate, one of the α carbons undergoes deprotonation and functions as the nucleophile that attacks the ester electrophile on the other end of the chain.
The nucleophilic enolate site is generated when a base abstracts the α proton adjacent to one of the ester groups.
An intramolecular attack on the carbonyl carbon of the other ester group forms a cyclic intermediate. Next, the carbonyl bond reforms with simultaneous loss of the alkoxide ion to give the cyclic β-ketoester.
The acidic hydrogen in the cyclic ketoester is deprotonated to give an enolate ion which on acidification gives the neutral β-ketoester.
15.29:
Intramolecular Claisen Condensation of Dicarboxylic Esters: Dieckmann Cyclization
Dieckmann cyclization is an intramolecular Claisen condensation of diesters. The reaction occurs in the presence of a base and generates a cyclic β-ketoester as the final product. Commonly, 1, 6 and 1, 7-diesters are preferred substrates for the reaction since the generated five, and six-membered cyclic β-keto esters are particularly more stable.
In the reaction, α carbon connected to one end of the ester ends serves as an enolate nucleophile after losing its proton to the base. The carbonyl carbon of the ester group at the other end of the same molecule functions as the electrophilic site. The enolate, through an intramolecular nucleophilic attack on the carbonyl carbon, cyclizes the molecule to form a stable ring intermediate. The intermediate reacts with the base and generates another enolate ion, which is neutralized to form the final β-ketoester. The second deprotonation step is the driving force for the reaction to go to completion.
The formed product can undergo alkylation and decarboxylation to produce substituted cyclic ketones.
