Condensation Darzens glycidic ester

Darzens glycidic ester condensation generally involves the condensation of an aldehyde or ketone 2 with the enolate of an a-halo ester 1 which leads to an a,P-epoxy ester (a glycidic ester) (3). Thus the reaction adds two carbons to the electrophile however, the reaction has been primarily developed as a one-carbon homologation method. That is, subsequent to the condensation, the ester is saponified and decarboxylation ensues to give the corresponding aldehyde or ketone 5.2 

Several years ago, there was much debate concerning the mechanism of the Darzens condensation.2.3 The debate concerned whether the reaction employed an enolate or a carbene intermediate. In recent years, significant evidence that supports the enolate mechanism has been obtained, wherein the stabilized carbanion (11) of the halide (10) is condensed with the electrophile (12) to give diastereomeric aldolate products (13,14), which subsequently cyclize via an internal Sn2 reaction to give the corresponding oxirane (15 or 16). The intermediate aldolates have been isolated for both a-fluoro- and a-chloroesters 10. 

Furthermore, in analogy to the aldol reaction, a-chloro-a,3-unsaturated esters have been observed—likely the result of 3-elimination of water from the intermediate halohydrin. For example, when benzaldehyde is condensed with the enolate of 17, chloride 19 was obtained.  

The ratio of products 15 and 16 is dependent on the structures, base, and the solvent. The kinetics of the reaction is likewise dependant on the structures and conditions of the reaction. Thus addition or cyclization can be the rate-determining step. In a particularly noteworthy study by Zimmerman and Ahramjian, it was reported that when both diastereomers of 20 were treated individually with potassium r-butoxide only as-epoxy propionate 21 was isolated. It is postulated that the cyclization is the rate-limiting step. Thus, for these substrates, the retro-aldolization/aldolization step reversible.  

An explanation for the stereoselectivity of the reaction involves optimal overlap of the 7t-orbital of the carbonyl with the developing electron rich p-orbital on C2 during the Sj,j2 displacement of the chloride by the alkoxide (24). Thus, orbital overlap imposes conformational constraints in the transition state that leads to nonbonding interactions disfavoring transition state 15P 

Tbe Darzens Glycidic Ester Condensation. When an a-halo ester is treated with base and the resulting enolate anion condensed with a carbonyl derivative, the product is an alkoxide. This nucleophilic species can displace the halogen intramolecularly to produce an epoxide, which forms the basis of a classical reaction known as the Darzens glycidic ester condensation. 13S Reaction of ethyl a-chloroacetate and sodium ethoxide, in the presence of benzaldehyde. generated the usual alkoxide (221). Intramolecular displacement 

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Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Rosen, T. Darzens Glycidic Ester Condensation In Comprehensive Organic Synthesis Trost, B. M. Fleming, I., Eds. Pergamon Oxford, 1991, vol. 2, pp 409-439. (Review). 

Myers, B. J. Darzens Glycidic Ester Condensation In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 15—21. (Review). 

Darzens Condensation (Darzens-Claisen Reaction, Darzens Glycidic Ester Condensation)... 

Dalton s law of partial pressures, 12 Darzens glycidic ester condensation, 906J, 907... 

Glycidic esters are prepared by the reaction of an aldehyde or ketone with an a-haloester in the presence of base (sodium ethoxide, sodamide, finely divided sodium or potassium t-butoxide) (the Darzens glycidic ester condensation). 

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