Wittig reaction Horner-Wadsworth-Emmons reaction

For the synthesis of alkenes, the Wittig and Horner-Wadsworth-Emmons reactions have become important tools. Triphenylphosphine that is used in the Wittig reaction can be immobilized either on the polymer or can be used in solution for solid-phase chemistry (Scheme 3.18). The Horner-Wadsworth-Emmons reaction for example is used for the synthesis of aldehyde building blocks [261]. 

P-nucleophiles (— precursors for Wittig or Horner-Wadsworth-Emmons reaction)... 

Oxaphosphetane Fragmentation, Last Step of Wittig and Horner-Wadsworth-Emmons Reactions... 

Scheme 1. Schematic representation of the Wittig and Horner-Wadsworth-Emmons reactions. LG = leaving group.

Others they made by Wittig or Horner-Wadsworth-Emmons reactions such as the methoxyketone 45 from the phosphonate ester 44. The 78% yield is of pure E-enone 45. 

Introduction The extended enolate problem Kinetic and thermodynamic control Wittig and Horner-Wadsworth-Emmons Reactions Extended Aza-Enolates Extended Lithium Enolates of Aldehydes Summary a-Alkylation of Extended Enolates Reaction in the y-Position Extended Enolates from Unsaturated Ketones Diels-Alder Reactions Extended Enolates from Birch Reductions The Baylis-Hillman Reaction The Synthesis of Mniopetal F... 

Formation of C-N bond has raised of interest in the scientific community in the last 10 years. In this context, the formation of enamides is a valuable protocol. In addition to conventional approaches that include condensation of amides and aldehydes, addition of amides to alkynes, acylation of imines, Curtius rearrangement of a,jS-unsaturated acyl azides, amide Peterson olefination, and Wittig and Horner-Wadsworth-Emmons reactions, several transition metal-catalyzed methods have been developed that allow the synthesis of enamides.Inspired by the analogous arylation of amines catalyzed by palladium or copper complexes (Buchwald-Hartwig reaction), a new approach for the synthesis of enamides has been published recently, which allows to prepare enamides from readily available starting materials (amides and vinyl halides) proceeding under very mild conditions. Thus, we decided to test the Porco-Buchwald amidation of vinyl halides in our synthesis [144-146]. 

In 1990, Gorgues and coworkers [60,61] reported the earliest studies of extended TTFs by acetylene scaffolding 61, in order to decrease on-site Coulomb repulsion. The symmetrically substituted acetylenic analog 61 was prepared from a very reactive aldehyde (58) [62] by Wittig or Horner-Wadsworth-Emmons reactions (Scheme 8.8). The CV of 61 exhibited reversible one two-electron redox pan-corresponding to 61/61 . This behavior is different from the TTFVs series of 2, which is linked by an ethylene spacer, due to lack of electronic communication through the acetylenic bond in 61 ". ... 

The (Horner-)Wadsworth-Emmons reaction generally is superior to the Wittig reaction, and has found application in many cases for the synthesis of a ,/3-unsaturated esters, a ,/3-unsaturated ketones and other conjugated systems. Yields are often better then with the original Wittig procedure. However the Wadsworth-Emmons method is not suitable for the preparation of alkenes with simple, non-stabilizing alkyl substituents. 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

Although the Horner-Wadsworth-Emmons reaction is not an ylide reaction, it represents methodologically such an important supplement to the Wittig reaction discussed in Figure 9.3 that we include its discussion here. 

Horner-Wadsworth-Emmons Reactions of Phosphonate Anions. - As with the Horner modification of the Wittig reaction, the principal focus of papers that mention the Horner-Wadsworth-Emmons reaction relate to synthetic applications. The use of pressure to induce the synthesis of P-amino esters, p-thioesters and P-thionitriles via tandem Horner-Wadsworth-Emmons and Michael reactions has been reported. The reagent (l-tritylimidazol-4-yl)methylphosphonate (99) has been prepared and, when treated with aldehydes and ketones, affords (E)-vinylimidazoles in high yields. ... 

Related reactions Horner-Wadsworth-Emmons olefination, Homer-Wadsworth-Emmons olefination - Still-Gennari modification, Julia-Lithgoe olefination, Takai-Utimoto olefination, Tebbe oiefination, Wittig reaction, Wittig reaction - Schiosser modification ... 

Wittig/Horner-Wadsworth-Emmons reactions sometimes lead to low yields when the reactant bearing the stabilized carbanion is bound to the support via an ester Hnkage [499]. The presence of OH ions during the reaction or work-up may be responsible for cleavage of the product from the polymer. 

Standard Wittig/Horner-Wadsworth-Emmons reaction conditions (Table 8, entries 25, 26) [477] The method presented here yields predominantly (E)-alkenes. 

Other y-bromoesters such as 31 can be made by radical bromination13 with NBS (this too is a y reaction ) and used in similar Horner-Wadsworth-Emmons reactions. It does not matter if some reaction occurs at the y position of 29 or 33 as the Wittig elimination cannot occur on such an intermediate and it reverses. The products of these aldol reactions are dienes 30 and 34 and are usually made for use in Diels-Alder reactions. We shall return to this subject later in this chapter. 

You saw in the last section that the preparation of allylic sulfides by displacement of, say, a halide from an allylic system is likely to give the more stable allylic sulfide whichever allylic halide is used and that the corresponding allylic sulfoxides are made by oxidation of the sulfide. The same is true of phosphorus compounds 73 used in chapter 15 to make dienes of fixed configuration. If R = OR, 73 is an allylic phosphonate for the Horner-Wadsworth-Emmons reaction but if R = Ph, 73 is a phosphine oxide for the Wittig-Horner reaction. 

The unstable silyl ether in 232 was replaced by a more stable acetoxy ketone 233 which was not isolated. A Horner-Wadsworth-Emmons reaction was used for the Wittig-style olefination (chapter 15). A nitrile 234 replaced the carbonyl group in 230 as it was found easier to reduce nitriles in conjugative fashion. 

Where applicable, the Horner-Wadsworth-Emmons reaction is generally superior to the Wittig reaction with resonance-stabilized phosphonium ylides and it is employed widely in the preparation of a,(3-unsaturated esters and other conjugated systems. It often gives better yields than the Wittig reaction, the phosphonate esters are readily available and it has the practical advantage that the phosphate... 

The Horner-Wadsworth-Emmons reaction (or HWE reaction) is the reaction of stabilized phosphonate carbanions with aldehydes (or ketones) to produce predominantly -alkenes. In 1958, Horner published a modified Wittig reaction using phosphonate-stabilized carbanions [32]. Wadsworth and Emmons further defined the reaction [33]. Compared to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic and more basic. Likewise, phosphonate-stabilized carbanions can be alkylated, unlike phosphonium ylides. The dialkylphosphate salt by-product is easily removed by aqueous extradion. A reliable and versatile synthesis of a stilbene derivative, 2,2-aryl-substituted cinnamic acid esters, using the Wittig reaction was reported [34—36] (Figure 1.3). 

The Wittig synthesis of alkenes and variations of it, such as the Horner-Wadsworth-Emmons reaction, are now regarded as among the classic reactions of organic chemistry. Such reactions are of enormous importance because they produce alkenes of predictable structure under mild conditions. In performing some of the experiments in this chapter, you may be executing a functional group transformation that earned its discoverer a Nobel Prize in Chemistry (Sec. 18.2). 

Horner-Wadsworth-Emmons reaction. See also Wittig reaction defined, 295,298... 

HORNER - WADSWORTH - EMMONS Olelination Wittig type reaction of ptwsptionale stabilized carbanions with aldehydes or ketones to form olefins... 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

Syntheses follow a kind of bio-mimetic approach [283, 284] in building up the chain during a sequence of Wittig-type reactions or Horner-Wadsworth-Emmons olefination, adding two carbons to the chain at a time with either methyl- or ethyl-branches. As the final products need to be highly pure (E)-stereoisomers, reaction steps and purification need to be carefully controlled. 

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