Ketones Darzens glycidic ester condensation

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... 

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). 

The Darzens glycidic ester condensation involves the condensation of an aldehyde or ketone with an a-halo ester, in the presence of a base, to afford an a,3 epoxy ester (a glycidic ester ). The first synthesis of a glycidic ester was reported by Erlenmeyer in 1892 and is illustrative of the general reaction, as shown in equation (1). The reaction was subsequently developed and generalized by Darzens. Glycidic esters, in addition to undergoing transformations normally associated with epoxides, afford upon hydro-... 

The Darzens Glycidic Ester Condensation. When an aldehyde (or ketone) is allowed to react with the carbanion formed by proton abstraction from a halogenbearing carbon a to the carbonyl of an ester, RCO2R (this Chapter), an oxirane (epoxide) results. These compounds, containing an oxirane (epoxide) a,p to the carbon of the carbonyl of the ester, are known as glycidic esters. An accepted... 

Aldehydes and ketones condense with a-halo esters in the presence of bases to give ot,p-epoxy esters, called glycidic esters. This is called the Darzens condensation. The reaction consists of an initial Knoevenagel-type reaction (16-41), followed by an internal Sn2 reaction (10-13) ° ... 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

Darzen s reaction org chem Condensation of aldehydes and ketones with a-haloesters to produce glycidic esters. dar-zonz re.ak-shon ... 

Darzens reaction of (-)-8-phenylmethyl a-chloroacetate (and a-bromoacetate) with various ketones (Scheme 2) yields ctT-glycidic esters (28) with high geometric and diastereofacial selectivity which can be explained in terms of both open-chain or non-chelated antiperiplanar transition state models for the initial aldol-type reaction the ketone approaches the Si-f ce of the Z-enolate such that the phenyl ring of the chiral auxiliary and the enolate portion are face-to-face. Aza-Darzens condensation reaction of iV-benzylideneaniline has also been studied. Kinetically controlled base-promoted lithiation of 3,3-diphenylpropiomesitylene results in Z enolate ratios in the range 94 6 (lithium diisopropylamide) to 50 50 (BuLi), depending on the choice of solvent and temperature. ... 

Darzens condensation The coupling of an a-bromocarboxylate ester with an aldehyde or ketone under basic conditions to give a glycidic ester, i.e. an ester with an a, P-epoxide group. 

Synthesis of glycidic esters. The Darzens reaction1 fails with compounds such as acetaldehyde which give only self-condensation products. Borch2 has described a new procedure which is generally applicable. The a-bromo ester anion (2) is smoothly generated by reaction with lithium bis(trimethylsilyl)amide in THF at —78°. Addition of the aldehyde or ketone at —78° followed by workup affords the corresponding... 

Darzens condensation. Formation of a- and (i-epoxy esters (glycidic esters) by the condensation of aldehydes or ketones with esters of a-haloacids the corresponding thermally unstable glycidic acids yield aldehydes or ketones on decarboxylation. 

Early attempts to utilize acetaldehyde and monosubstituted acetaldehyde derivatives in the Darzens reaction were unsuccessful, presumably due to competitive base-catalyzed self-condensations of the aldehydes. It was subsequently reported Aat generation of the requisite bromo ester enolates with LHMDS at -78 °C provides a species which reacts with a variety of aldehydes and ketones to afford glycidic esters in good to excellent isolated yields (equation 25). ... 

Hydroxy-ester enolates are oxidized by iodine at — 78°C to give the least hindered oxiran. Thus, by generating the /3-hydroxy-ester from a ketone and acetate enolates, the overall conversion represents a stereoselective Darzens condensation. Glycidic esters can also be obtained from the corresponding nitriles via iminoether derivatives prepared by alkoxide-catalysed addition of alcohols to the nitrile group. 

When an aldehyde or a ketone is condensed with ethyl a-chloroacetate in the presence of sodium ethoxide, the product is an a,j8-epoxy ester called a glycidic ester. The synthesis is called the Darzens condensation. 

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