John McMurry, Professor Emeritus

23.9 • Intramolecular Claisen Condensations: The Dieckmann Cyclization

Intramolecular Claisen condensations can be carried out with diesters, just as intramolecular aldol condensations can be carried out with diketones (Section 23.6). Called the Dieckmann cyclization, this reaction works best on 1,6-diesters and 1,7-diesters. Intramolecular Claisen cyclization of a 1,6-diester gives a five-membered cyclic β-keto ester, and cyclization of a 1,7-diester gives a six-membered cyclic β-keto ester.

The first reaction converts diethylhexanedioate (1,6-diester) to ethyl-2-oxocyclopentanecarboxylate (eighty-two percent) and ethanol. Second reaction converts diethylheptanedioate (1,7-diester) to ethyl-2-oxo-cyclohexanecarboxylate and ethanol. The reagents are sodium hydroxide, ethanol and hydronium ion.

The mechanism of the Dieckmann cyclization, shown in Figure 23.6, is the same as that of the Claisen condensation. One of the two ester groups is converted into an enolate ion, which carries out a nucleophilic acyl substitution on the second ester group at the other end of the molecule. A cyclic β-keto ester product results.

Figure 23.6 MECHANISM

Mechanism of the Dieckmann cyclization of a 1,7-diester to yield a cyclic β-keto ester product.

A Dieckmann cyclization of a 1,7-diester. The reaction steps comprise deprotonation by base, nucleophilic attack, alkoxide loss, deprotonation to enolate, and final protonation to cyclic beta keto ester product.

The cyclic β-keto ester produced in a Dieckmann cyclization can be further alkylated and decarboxylated by a series of reactions analogous to those used in the acetoacetic ester synthesis (Section 22.7). Alkylation and subsequent decarboxylation of ethyl 2-oxocyclohexanecarboxylate, for instance, yields a 2-alkylcyclohexanone. The overall sequence of (1) Dieckmann cyclization, (2) β-keto ester alkylation, and (3) decarboxylation is a powerful method for preparing 2-substituted cyclopentanones and cyclohexanones.

Ethyl 2-oxocyclohexanecarboxylate reacts with allyl bromide in the presence of sodium ethoxide, forming 2-allylcyclohexanone. Further heating with hydronium ion, yields 2-allylcyclohexanone (eighty-three percent), C O 2, and ethanol.

Problem 23-14

What product would you expect from the following reaction?

Diethyl-4-methylheptanedioate reacts with sodium ethoxide (first step) and hydronium (second step) to give unknown products, depicted by a question mark.

Problem 23-15

Dieckmann cyclization of diethyl 3-methylheptanedioate gives a mixture of two β-keto ester products. What are their structures, and why is a mixture formed?

23.9 Intramolecular Claisen Condensations: The Dieckmann Cyclization