In the Darzens condensation

Also in 1978, Wynberg and Hummelen used the benzyl quininium chloride 185a as a chiral phase-transfer catalyst in the Darzens condensation [191]. In the... 

In the Reformatsky reaction, an ester with an a-halogeno substituent is treated with zinc, and so forms a masked carbanion, which in turn can react with a carbonyl compound to form a 3-hydroxyester. In the Darzens condensation, an a-halogenoester, on treatment with a base, reacts with a carbonyl compound to form an a,P-epoxyester. 

It is valuable when trying to illustrate the geometry of the formation of a three-membered ring, as in the Darzens condensation. 

For another example of overlap control, in the Darzens condensation, see Vol. 2, Chap. 1.13. 

Table 2 Temperature Dependence of Cis Jrans Isomer Ratio in the Darzens Condensation ...

Under phase-transfer conditions a quatemized cinchona alkaloid is used in the Darzens condensation. ... 

The epoxy esters formed in the Darzens condensation have been used in the synthesis of ketones and aldehydes. The acids formed by saponification of the esters... 

Epoxidations. In contrast to dimethylsuUbnlum methylide, EDSA usually does not react with aldehydes or ketones in a 1,2-sense to generate epoxides. However, under certain conditions, electron-deficient carbonyls do undergo this reaction. Thus EDSA can be considered an alternative (albeit of limited scope) to a-haloacetic acid esters in the Darzens condensation (eq 3). ... 

PROBLEM 19.65 Account for the formation of both stereoisomers in the Darzens condensation shown below ... 

Another calixarene-based phase-transfer catalyst was designed by Srivastava and Srivastava [20]. In that study, two different quaternary ammonium salts of calix [4]arene (Calix[4]arene 2a and 2b) were employed as a catalyst in the Darzens condensation to synthesize a,p-epoxy carbonyl compounds (see Fig. 27.5). It was found that these phase-transfer catalysts exhibited significant catalytic activity, especially when the calix[4]arene with long aUcyl chain ( -butyl) was chosen (see Table 27.3). 

This, the Darzens reaction, is useful in other circumstances (frames 280-1) but a nuisance here. We must use some means to make the ketone act as the nucleophile in the initial condensation. One effectiye way is to conyert it into an enamine. Draw a mechanism for this reaction. 

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. 

In recent years, several modifications of the Darzens condensation have been reported. Similar to the aldol reaction, the majority of the work reported has been directed toward diastereo- and enantioselective processes. In fact, when the aldol reaction is highly stereoselective, or when the aldol product can be isolated, useful quantities of the required glycidic ester can be obtained. Recent reports have demonstrated that diastereomeric enolate components can provide stereoselectivity in the reaction examples include the camphor-derived substrate 26, in situ generated a-bromo-A -... 

The Darzens condensation reaction has been used with a wide variety of enolate equivalents that have been covered elsewhere. A recent application of this important reaction was appljed toward the asymmetric synthesis of aziridine phosphonates by Davis and coworkers.In this application, a THF solution of sulfinimine 34 (0.37 mmol, >98% ee) and iodophosphonate 35 (0.74 mmol) was treated with LiHMDS (0.74 mmol) at -78 °C to give aziridine 36 in 75% yield. Treatment of 36 with MeMgBr removed the sulfinyl group to provide aziridine 37 in 72% yield. 

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) ° ... 

Reactions of carbanions, anions of weak organic acids (e.g., indole or carbazole), and dihalocarbenes may be carried out in liquid-liquid systems, in which concentrated aqueous sodium hydroxide is the aqueous phase. The term phase transfer catalysis is mechanistically incorrect these are often referred to as catalytic two-phase systems. Numerous reactions of carbanions including alkylation, nitroarylation, addition, the Darzens condensation, cyclopropanation, and also a variety of reactions of dihalocarbenes are conveniently carried out in this way. 

Later Takahashi et al.19 have reported an alternative synthesis of the cyanooxirane (40a,b) by carrying out the reaction between decyl bromide and potassium cyanide in the presence of quaternary ammonium catalysts. Compounds prepared by this method are similar to those obtained by the Darzens condensation with benzaldehyde in a two-phase system.78... 

The stereochemistry of the Darzene condensation has received considerable attention in the literature. Early papers devoted to this aepeot of the reaction were those of Berson,1 Wasserman and oo-workere,1807-1808 and Stevens.,Ma From the work of these authors... 

Mechanism. The mechanism of the Darzens condensation has ran thoroughly discussed in a roviow by Ballester,47 who considers a -umber of older proposals and cogently discards each of them in turn. hhough his arguments will not be reproduced here in their entirety, ".e preferred mechanism for the general case appears to be as shown in j i- (162). 

An open-transition-state model is proposed for the Darzens condensation of ketones with (—)-8-phenyhnenthyl a-chloroacetate the diastereoselectivity observed is explained in terms of a 71-aryI interaction between the enolate and phenyl moieties.78... 

Whilst simple alkylations of enolates and Michael additions have been successfully catalyzed by phase-transfer catalysts, aldol-type processes have proved more problematic. This difficulty is due largely o the reversible nature of the aldol reaction, resulting in the formation of a thermodynamically more stable aldol product rather than the kinetically favored product. However, by trapping the initial aldol product as soon as it is formed, asymmetric aldol-type reactions can be carried out under phase-transfer catalysis. This is the basis of the Darzens condensation (Scheme 8.2), in which the phase-transfer catalyst first induces the deprotonation of an a-halo... 

Very recently, Belokon and North have extended the use of square planar metal-salen complexes as asymmetric phase-transfer catalysts to the Darzens condensation. These authors first studied the uncatalyzed addition of amides 43a-c to aldehydes under heterogeneous (solid base in organic solvent) reaction conditions, as shown in Scheme 8.19 [47]. It was found that the relative configuration of the epoxyamides 44a,b could be controlled by choice of the appropriate leaving group within substrate 43a-c, base and solvent. Thus, the use of chloro-amide 43a with sodium hydroxide in DCM gave predominantly or exclusively the trans-epoxide 44a this was consistent with the reaction proceeding via a thermodynamically controlled aldol condensation... 

Colonna et al. reported that up to 62% ee can be achieved when the Darzens condensation of aromatic aldehydes with phenacyl chlorides is carried out in the presence of bovine serum albumin R. Annunziata, S. Banfi, S. Colonna, Tetrahedron Lett. 1985, 26, 2471-2474. 

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