6.5: Intramolecular Claisen Condensations - The Dieckmann Cyclization
- Page ID
- 469403
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The Dieckmann Cyclization
Diesters can undergo an intramolecular reaction, called the Dieckmann condensation, to produce cyclic beta-keto esters. This reaction works best with 1,6-diesters, which produce five-membered rings, and 1,7-diesters which produce six membered rings.
Examples
Mechanism
The mechanism of the Dieckmann condensation is the same as a Claisen condensation. An alkoxide base removes an alpha-hydrogen from one of the esters to form an ester enolate. The enolate then adds to the carbonyl carbon of the other ester to form a tetrahedral alkoxide intermediate. The alkoxide reforms the carbonyl bond which causes the elimination of the –OR leaving group and forms a cyclic beta-keto ester. The high acidity of the beta-keto ester allows it to be deprotonated by the reactions base to form a second enolate. Like the Claisen condensation, this deprotonation step drives the equilibrium towards the products and is required for the reaction to occur. A full equivalent of base is necessary during this reaction.
1) Enolate formation
2) Nucleophilic attack
3) Removal of leaving group
4) Deprotonation
5) Protonation
Further Reactions of the Dieckmann Cyclization Product
The cyclic beta-keto ester product of a Dieckmann cyclization can be modified by reaction similar to those used in the acetoacetic ester synthesis (Section 22-7). The acidic alpha-hydrogens of the beta-keto ester allow it to easily be deprotonated and alkylated in an alpha-substitution reaction. Having a carbonyl group in the beta position allows the ester to be removed through decarboxylation. The combination of these three reactions (1) Dieckmann cyclization, (2) alpha alkylation, and (3) decarboxylation provides an efficient method for preparing 2-substituted cyclopentanones and cyclohexanones.