Dieckmann condensation mechanisms

PROBLEM 19.67 Provide structures for compounds A-D. PROBLEM 19.63 Here is a reverse Dieckmann condensation. Mechanisms are not required. 

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

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

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. 

Bicyclic keto esters can easily be prepared by a process called a,a -annulation.29 Thus, treatment of the enamine of cyclopentanone (64) with ethyl a-(bromomethyl)acrylate (98) affords, after work-up, the bicyclic keto ester (99) in 80% yield (equation IS).2911 The mechanism probably involves an initial Michael addition and elimination (or a simple Sn2 or Sn2 alkylation) followed by an intramolecular Michael addition of the less-substituted enamine on the acrylate unit. The use of the enamine of 4,4-bis(ethoxycarbonyl)cyclohexanone (100 equation 26) with (98) gives a 45% yield of the adaman-tanedione diester (101) (yield based on 100 70% when based on 98) via a,a -annulation followed by Dieckmann condensation.29 Enamines of heterocyclic ketones can also serve as the initial nucleophiles, e.g. (102) and (103) give (105) via (104), formed in situ, in 70% yield (Scheme 11 ).29>... 

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

Intramolecular Claisen condensations, called Dieckmann condensations, are ringclosing reactions that yield 2-cyclopentanone carboxylic esters (Figure 10.52) or 2-cyclohexanone carboxylic esters. The mechanism of the Dieckmann condensation is, of course, identical to the mechanism of the Claisen condensation (Figure 10.51). To ensure that the Dieckmann condensation goes to completion, the presence of a stoichiometric amount of base is required. As before, the neutral /3-ketoester (B in Figure... 

Key Mechanism 22-12 The Claisen Ester Condensation 1071 22-13 The Dieckmann Condensation A Claisen Cyclization 1074 22-14 Crossed Claisen Condensations 1074 22-15 Syntheses Using /3-Dicarbonyl Compounds 1077 22-16 The Malonic Ester Synthesis 1079 22-17 The Acetoacetic Ester Synthesis 1082 22-18 Conjugate Additions The Michael Reaction 1085 Mechanism 22-13 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

Propose mechanisms for the two Dieckmann condensations just shown. 

Problem 17.32 Ethyl pimelate, C2H3OOC(CH2)3COOC2H5, reacts with C2H50 Na+ (Dieckmann condensation) to form a cyclic keto ester, C9Hl403. Supply a mechanism for its formation and compare the yields in ethanol and ether as solvents. ... 

To most organic chemists the term Claisen condensation implies the self-condensation of esters in the presence of sodium ethoxide to give 0-ketoesters. A Dieckmann condensation is a special Claisen condensation in which an ester of a dibasic acid undergoes intramolecular condensation to produce a cyclic jS-ketoester. From the point of view of mechanism, however, this idea of a Claisen condensation is perhaps unnecessarily limited, for there are a number of extremely closely related reactions which involve compounds other than esters, and bases other than sodium ethoxide. In all these transformations, the essential feature of the reaction is the addition of a carbanion to a carbonyl group, followed by the loss of a negative ion from the seat of reaction. 

The mechanism of the Dieckmaim condensation is the same as the mechanism of the Claisen condensation. The only difference between the two reactions is that the attacking enolate and the carbonyl group undergoing nucleophilic attack are in different molecules in the Claisen condensation, but are in the same molecule in the Dieckmaim condensation. The Dieckmann condensation, like the Claisen condensation, is driven... 

Keto esters are capable of undergoing cyclization reactions similar to the Dieckmann condensation. Write a mechanism for the following reaction. 

The mechanism of a Dieckmann condensation is identical to the mechanism we described for the Claisen condensation. An anion formed at the a-carbon of one ester in Step 1 adds to the carbonyl of the other ester group in Step 2 to form a tetrahedral carbonyl addition intermediate. This intermediate ejects ethoxide ion in Step 3 to regenerate the carbonyl group. Cyclization is followed by formation of the conjugate base of the j8-ketoester in Step 4, just as in the Claisen condensation. The j8-ketoester is isolated after acidification with aqueous acid. 

There are few mechanistic studies for the Dieckmann condensation. " The reaction can simply be described as an intramolecular Claisen condensation and hence entirely reversible. The summation of the consensus for its mechanism is as follows the reaction is initiated by anion formation through the abstraction of the most acidic proton on the a-carbon to one of the di-... 

Tanabe et al. proposed mechanism for the dehydration-type Ti-Dieckmann condensation and thiophene formation is shown below. 

The Thorpe-Ziegler cyclization is characterized by a relatively straightforward mechanism. As demonstrated below, deprotonation of dinitrile 1 results in the formation of the anionic species 2. Intramolecular cyclization in a manner similar to the well-known Dieckmann condensation yields 3. Workup under aqueous conditions then produces imine 4, which immediately tautomerizes to the conjugated enamine 5. 

Notice once again that the product is just a P-keto ester. This reaction has its own name (the Dieckmann condensation). But it is really just an intramolecular Claisen condensation. Therefore, the steps of this mechanism are identical to the steps of a regular Claisen condensation. Propose a mechanism for the Dieckmann condensation. Try to do it without looking back at your previous work. You will need a separate piece of paper to record your answer. 

EtOjCCHjCHjCOOEt does not undergo a simple Dieckmann condensation, but instead dimerizes to give 17.70. Explain, writing a full mechanism ... 

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 then carries out a nucleophilic acyl substitution on the second ester group at the other end of the molecule. A cyclic /3-keto ester product results. 

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