15.29 : ジカルボン酸エステルの分子内クライゼン縮合: ディークマン環化

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.