Condensations Darzens

The Darzens condensation is an aldol-like reaction in which the aldolate product closes to give an epoxy ketone. The reaction has been achieved with moderate 

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Early efforts to partially synthesize 20-keto and 17a-hydroxy-20-keto steroids led to ring D-expanded products isomeric with the desired compounds. Darzens condensation of 3/5-hydroxyandrost-5-en-17-one acetate (75) with ethyl a,a-dichloropropionate, followed by alkali treatment and decarboxylation, gives both the expected 3j5-hydroxypregn-5-en-20-one (78) and an isomer now known to be 17a-methyl-D-homo-17-ketone (79).36,37a alternative route for the introduction of the two carbon side chain, Ruzicka... 

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 -... 

Interestingly, phase-transfer catalysts including crown ethers have been used to promote enantioselective variations of Darzens condensation. Toke and coworkers showed that the novel 15-crown-5 catalyst derived from d-glucose 33 could promote the condensation between acetyl chloride 31 and benzaldehyde to give the epoxide in 49% yield and 71% A modified cinchoninium bromide was shown to act as an effective phase transfer catalyst for the transformation as well. ... 

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. 

Instead of a-halo esters, related reactants can be used e.g. the a-halo derivatives of ketones, nitriles, sulfones and A,A-disubstituted amides. The Darzens condensation is also of some importance as a synthetic method because a glycidic acid can be converted into the next higher homolog of the original aldehyde, or into a branched aldehyde (e.g. 5) if the original carbonyl substrate was a ketone ... 

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) ° ... 

A very interesting organocatalyzed one-pot Michael addition/aldol condensation/Darzens condensation has been reported for the asymmetric synthesis of epoxy-ketones <06JA5475>. An initial asymmetric Michael condensation between 16 and 17 is catalyzed by proline derivative 18. Intermediate 19 then undergoes an aldol condensation followed by a stereoselective Darzens condensation to provide epoxy-ketone 20 in moderate yield and with surprisingly good enantiomeric excess. 

The asymmetric Darzens condensation, which involves both carbon-carbon and carbon-oxygen bond constructions, was realized by use of the chiral azacrown ether 75als2,s ,ss and the quaternary ammonium salts derived from cinchona alka-loids159"621 under phase transfer catalyzed conditions. The a,p-epoxy ketone 80 (R=Ph) was obtained with reasonable enantioselectivity by the reaction of... 

The cyclic a-chloro ketone 81 which forms the (Z)-enolate only also underwent the asymmetric Darzens condensation with various aldehydes by use of the Merck catalyst 7 (R=4-CF3, X=Br) under analogous conditions to furnish the a,(3-epoxy ketones 82 with up to 86 % ee,160611 as shown in Scheme 25. It should be noted that this high enantioselectivity was attained by the reaction at room temperature. 

P. Bako, A. Szolloy, P. Bombicz, L. Toke, Asymmetric C-C Bond Forming Reactions by Chiral Crown Catalysts Darzens Condensation and Nitroalkane Addition to the Double Bond , Synlett 1997, 291-292. 

S. Arai, T. Shioiri, Catalytic Asymmetric Darzens Condensation under Phase-Transfer-Catalyzed Conditions , Tetrahedron Lett. 1998, 39, 2145-2148. 

Dartanol, 24 536 Dart impact strength, 20 429 Darzens-Claisen condensation, 14 570 Darzens condensation, 10 505 DAS antibody, 14 145, 147 DAS-hemisuccinate (DAS-HMS), 14 144 DASH-Sodium Study, 22 813 Data, growth of, 21 612-613. See also Decay data... 

A degree of stereoselective control of the course of a reaction, which is absent or different from that prevalent when the reaction is conducted in the absence of quaternary ammonium salts, may be achieved under standard phase-transfer catalysed reaction conditions. The reactions, which are influenced most by the phase-transfer catalyst, are those involving anionic intermediates whose preferred conformations or configurations can be controlled by the cationic species across the interface of the two-phase system. For example, in the base-catalysed Darzens condensation of aromatic aldehydes with a-chloroacetonitriles to produce oxiranes (Section 6.3), the intermediate anion may adopt either of the two conformations, (la) or (lb) which are stabilized by interaction across the interface by the cations (Scheme 12.1) [1-4]. 

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. ... 

Epoxidations and Darzens Condensations The asymmetric catalytic epoxida-tion of a,p-unsaturated ketones using cinchona alkaloid-derived catalysts was introduced in the 19708. However, high levels of enantioselectivity were achieved only 20 years later, when Lygo, Arai, 2-t94 others P ... 

Darzens condensation using crown ethers and cinchona alkaloids-derived catalysts, respectively, obtaining epoxides with moderate enantioselectivity. 

Darzens condensation, 374 Dazadrol, 257 Debrisoquin, 374 Decoquinate, 368 Dehydrogenation,... 

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

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 Darzens condensation of chloromethyl p-tolysulfone has also been successfully employed for the synthesis of a,p-epoxysulfone 21 (Scheme 11), which undergo nucleo-... 

B. Danena CmtlenaoHon -OlycHie Eaters The most frequently used method for synthesizing glycidic esters is Darzene condensation, which is based on a discovery in 1SU3 by Ertenmeyer404 that sodium-catalyzed condensation between benz-aldehyde and ethyl -chloroacetate yields tho ct,J -epoxy ester ethyl p-phenylglycidate (Eq. 145). 

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