The Dieckmann Condensation

An intramolecular Claisen condensation is called a Dieckmann condensation. For example, when diethyl hexanedioate is heated with sodium ethoxide, subsequent acidification of the reaction mixture gives ethyl 2-oxocyclopentanecarboxylate  

The enolate ion attacks the carbonyl group at the other end of the chain. 

The ethoxide Ion removes the acidic hydrogen located between two carbonyl groups. This favorable equilibrium drives the reaction. 

Addition of aqueous acid rapidly protonates the anion, giving the final product. 

Chapter 19 Condensation and Conjugate Addition Reactions of Carbonyl Compounds 

---

Electrostatic potential map for the enolate initially formed in the Dieckmann condensation of diethyl adipate shows most negatively-charged regions (in red) and less negatively-charged regions (in blue). 

The Dieckmann condensation of diethyl adipate yields a keto-ester product. 

Next, calculate the energy for each step in your mechanism. Were your predictions correct Is the Dieckmann condensation a thermodynamically favorable process overall ... 

Carboxylic esters 1 that have an a-hydrogen can undergo a condensation reaction upon treatment with a strong base to yield a /3-keto ester 2. This reaction is called the Claisen ester condensation or acetoacetic ester condensation, the corresponding intramolecular reaction is called the Dieckmann condensation ... 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

A functional group is introduced to the polystyrene 10 by chloromethylation Blanc reaction) in order to allow for reaction with the substrate 11. The polymer-bound diester is then treated with base to initiate the Dieckmann condensation. 

Condensations Highly atom economical since small molecules of water or alcohol are liberated Atom economy increases as the molecular weights of the combining fragments increases For cyclization reactions such as the Dieckmann condensation and the synthesis of cyclic ethers from straight chain diols the atom economy increases with increasing ring size... 

Figure 5.9 Mass indices and environmental factors E for the Dieckmann condensation reactions depicted in Scheme 5.5, using the software EATOS Results for laboratory (L) (f 0.2 kg) and operation (O) (f l 500 kg) scale, as well as for a literature protocol (Lit.) (scale 0.01 2 kg ) are shown.

The intramolecular version of ester condensation is called the Dieckmann condensation.217 It is an important method for the formation of five- and six-membered rings and has occasionally been used for formation of larger rings. As ester condensation is reversible, product structure is governed by thermodynamic control, and in situations where more than one product can be formed, the product is derived from the most stable enolate. An example of this effect is the cyclization of the diester 25.218 Only 27 is formed, because 26 cannot be converted to a stable enolate. If 26, synthesized by another method, is subjected to the conditions of the cyclization, it is isomerized to 27 by the reversible condensation mechanism. 

This is the most convenient way to prepare quinuclidone hydrochloride. The second step illustrates the conversion of an N-alkyl-pyridinium salt to an N-alkylpiperidine. The third step illustrates the formation of a bicydic system by the Dieckmann condensation. 

The Dieckmann condensation is the intramolecular version of the Claisen condensation. 

The term condensation refers to the joining of two molecules with the splitting out of a smaller molecule. The Claisen condensation is used extensively in the synthesis of dicarbonyl compounds. In biochemistry it is used to build fatty acids in the body. The Dieckmann condensation, the crossed Claisen condensation, and others (with other carbanions) cire variations of the Claisen condensation. In this section we briefly look at these variations. 

The intramolecular version of ester condensation is called the Dieckmann condensation,119 It is an important method for the formation of five- and six-membered rings and has occassionally been used for formation of larger rings. Entries 3-6 in Scheme 2.13 are illustrative. 

Interestingly, the dienolate generated from di-/er/-butyl adipate underwent oxidative cycliza-tion with copper(II) chloride to afford di-/m-butyl cyclobutane-l,2-dicarboxylate (12) in 21 % yield, together with the competitive Dieckmann product (30%) as well as unreacted starting material (17%).20 The formation of the cyclobutane diester is presumably due to the steric hindrance of the /e/v-butyl groups, which impedes the Dieckmann condensation and thus favors, to some extent, an oxidative coupling reaction.20... 

When the two ester groups involved in the condensation are in the same molecule, the product is a cyclic p-keto ester and the reaction is called the Dieckmann condensation.1692... 

This interesting reaction is especially useful for the synthesis of medium- and large-ring compounds from dicarboxylic esters, and is effective for ring sizes that cannot be made by the Dieckmann condensation or decarboxylation (Section 18-1 OB). Radical anions formed by addition of sodium to the ester... 

The complex WOCI4—Cp2TiMe2 was used for the metathesis of ethyl oleate (51) to give diethyl 9-octadecenedioate (52). Civetone (53) was synthesized by the Dieckmann condensation of this diester, followed by decarboxylation [20], Homometathesis of terminal alkenes is useful, because it yields symmetric internal alkenes and ethylene, which can be removed easily. Metathesis of 10-undecenoate (54) proceeds smoothly to give the diester 55 [20],... 

The base-catalyzed intramolecular condensation of a diester. The Dieckmann Condensation works well to produce 5- or 6-membered cyclic i-keto esters, and is usually effected with sodium alkoxide in alcoholic solvent. 

In the absence of MesSiCI, the Dieckmann condensation in Figure Si3.14 proceeds faster than the corresponding acyloin condensation. 

Fig. 13.58. Mechanism of a Dieckmann condensation. The Dieckmann condensation is an intramolecular Claisen condensation.

---