Ester condensation Dieckmann cyclization

Cyclohexanone-2-carboxylic esters. The reagent acts as a condensation catalyst for twofold Michael additon of a donor to an acrylate ester and Dieckmann cyclization of the 1 2 adducts. However, NaOMe has the same capability therefore, Na2pe(CO)4 is not unique. 

Dieckmann cyclization (Section 21 2) An intra molecular analog of the Claisen condensation Cy die p keto esters in which the ring is five to seven membered may be formed by using this reaction... 

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, the reaction works best on 1.6-diesters and 1,7-diesters. Intramolecular Claisen cyclization of a 1,6-diester gives a five-membered cyclic /3-keto ester, and cyclization of a 1,7-diester gives a six-membered cyclic /3-keto ester. 

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. 

Dieckmann cyclization reaction (Section 23.9) An intramolecular Claisen condensation reaction to give a cyclic /3-keto ester. 

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. 

An interesting variation of the Dieckmann cyclization involves vinylogous activation of a methyl group in a 2-butenyl ester. Reaction of an a-halo ester with the enethiol formed by treatment of an acetoacetic ester, which may be substituted at the a-position, with hydrogen sulfide produces (92) in satisfactory yield. Treatment of these compounds with sodium in benzene produced the 4-hydroxythiophene-2-acetic acids (94) (40JCS1385). The product undoubtedly involved the intermediate (93), in which the activated methyl goup has condensed with the ethoxycarbonyl group in typical Claisen fashion. 

Fluorinated esters have synthetic utility m Claisen condensations [24, 25] (equation 21) and Dieckmann cyclizations [26]. 

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... 

The Claisen ester condensation (Sections 22-12 through 22-14) (Cyclizations are the Dieckmann condensation.)... 

Fluorinated esters have synthetic utility in Claiscn condensations, c.g. formation of 26,28,29 and Dieckmann cyclizations.30... 

An example is the synthesis of ethyl a-ethoxalylpropionate (R = CH,) in 70% yield. Ethyl oxalate and ethyl succinate form ethyl a-ethoxalyl-succinate (83%). In a mixed ester condensation, the use of a more reactive ester, such as the phenyl or biphenyl ester, helps to prevent side reactions. Simple heterocyclic esters, namely, ethyl nicotinate and ethyl 8-quinolinecarboxylate, undergo the mixed ester condensation in good yields. The internal condensation of ethyl adipate to give 2-carbethoxycyclopentanone (Dieckmann reaction) is an example of cyclization (81%). ... 

The Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a /3-keto ester product. Mixed Claisen condensations between two different esters are successful only when one of the two partners has no acidic a hydrogens (ethyl benzoate and ethyl formate, for instance) and thus can function only as the acceptor partner. Intramolecular Claisen condensations, called Dieckmann cyclization reactions, provide excellent syntheses of five- and six-membered cyclic /3-keto esters starting from 1,6- and 1,7-diesters. 

Bixchler Napiralski, Dieckmann cyclization [15], Suzuki reaction [48], Wittig reaction, ozonolysis, condensation, esterification, nucleophilic substitution [49], Henry reaction, 1.3-dipolar cyclo-addition, electrophilic addition [50], oxidation chloride -> aldehyde [50], sulfide —> sulfone [51], alcohol —> ketone, Arbuzov reaction (phosphine-phosphorox-ide) [52], reduction hydration [45], ester -> alcohol [49, 53]... 

Dieckmann cyclization [1,912, after citation of ref. 6]. In extending his work with Leonard,6 Schimelpfenigf,a used the reagent to effect Dieckmann condensation of esters of p-phcnylenedicarboxvlic acids to form ketones of paracyclophanes ... 

An important variation of the ester condensation is due to Dieckmann.765 It consists of a cyclization when two ester groups are attached to the same chain. For example, ethyl 2-oxocyclopentanecarboxylate is obtained from diethyl adipate in this way 752... 

A second synthesis has been described of slaframine (11), the amine which causes excessive salivation in livestock foraging on red clover infected with Rhizoctomia leguminicola. Condensation of L(-l-)-glutamic acid with acrylonitrile, followed by esterification, gave ethyl iV-()5-ethoxycarbonylethyl)-5-oxopyrrolidine-2-car-boxylate (12), which on Dieckmann cyclization, hydrolysis, and decarboxylation afforded the racemic 3-oxopyrrolidine acid (13). Platinum-catalysed hydrogenation of the hydrochloride of (13) in methanol solution gave the alcohol-ester... 

The preparation of thionan-5-one (143), in very poor yield, has been reported by the Dieckmann cyclization of 3-carboxyethylpropyl-4-carboxyethylbutyl sulfide <62JA2814>. The nine-membered aryl-fused rings (160) and (161) have been prepared by intramolecular condensation reactions between methyl ketones and methyl esters, using sodium hydride in boiling toluene (Scheme 14) <87CB1151>. 

Aldehyde, Ketone, and Ester Enolates 867 Enolate Regiochemistry 872 The Aldol Condensation 873 Mixed Aldol Condensations 878 Chalcones From the Mulberry Tree to Cancer Chemotherapy 880 The Claisen Condensation 882 Intramolecular Claisen Condensation The Dieckmann Cyclization 884 Mixed Claisen Condensations 885 Acylation of Ketones with Esters 886 Alkylation of Enolates 887 The Acetoacetic Ester Synthesis 889 The Malonic Ester Synthesis 891 Alkylation of Chiral Enolates 893 Enolization and Enol Content 895 a Halogenation of Aldehydes and Ketones 900... 

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