Wittig or Horner-Wadsworth-Emmons

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

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. 

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 ". ... 

Important and widely used variants of the Wittig reaction are based on carbanionic organophosphorus reagents, and are known as the Wadsworth-Emmons reaction, Wittig-Horner reaction or Horner-Wadsworth-Emmons reaction. As first reported by Horner, carbanionic phosphine oxides can be used today carbanions from alkyl phosphonates 13 are most often used. The latter are easily prepared by application of the Arbuzov reaction. The reactive carbanionic species—e.g. 14 —is generated by treatment of the appropriate phosphonate with base, e.g. with sodium hydride ... 

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. 

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]. 

Reaction with aldehydes or ketones (such as benzaldehyde) in the presence of base gave the olefination product 556 (in 84% yield).502 These variations have come to be called the Horner-Wadsworth-Emmons modiflcation of the Wittig reaction, or Horner-Wadsworth-Emmons olefination.503 It is sometimes called Horner-Emmons olefination. 

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]. 

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

Several other anionic/pericyclic domino processes use a Horner-Wadsworth-Emmons (HWE) or a Wittig olefmation as the first step. 

Horner-Wadsworth-Emmons or Horner-Wittig-Emmons 2-iodoxybenzoic acid... 

Phosphonate esters can be deprotonated with sodium hydride or alkoxide anions to give enolate-type anions that react well with aldehydes or ketones to give -alkenes. Alkene-forming reactions with phosphonates are called Horner-Wadsworth-Emmons (or Horner-Emmons, Wadsworth-Emmons, or even Horner-Wittig) reactions. This example is a reaction that was used by some Japanese chemists in the synthesis of polyzonimine, a natural insect repellent produced by millipedes. 

An important addition to the Wittig tran -olefination procedure is the introduction of phosphonate-stabilized carbanions as olefin-forming reagents, referred to as the Horner-Wadsworth-Emmons or HWE reaction. The HWE olefination offers several advantages over the Wittig reaction using stabilized ylides ... 

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. 

Rehwinkel, H., Skupsch, J., and Vorbrtiggen, H., E- or Z-selective Homer-Wittig reactions of suhsti-tuted bicyclo[3.3.0]octane-3-ones with chiral phosphonoacetates. Tetrahedron Lett., 29, 1775, 1988. Tiillis, J.S., Vares, L., Kann, N., Norrby, P.-O., and Rein, T., Reagent control of geometric selectivity and enantiotopic group preference in asymmetric Horner-Wadsworth-Emmons reactions with meso-dialdehydes, J. Org. Chem., 63, 8284, 1998. 

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. 

Some of the disadvantages of the Wittig reaction can be overcome by use of the Horner-Wadsworth-Emmons reaction or, in brief, the Horner-Emmons reaction [6,14-16]. The modification of the Wittig process makes use of a phosphonate-stabilized carbanion instead of a phosphorus ylide it is discussed in Section E. 

Fluprostenol was marketed in form of its racemate by ICI as a contraceptive in the veterinary sector. The synthetic route developed for this product proceeds via the Corey lactone, whereby the side-chains are built up using Horner-Wadsworth-Emmons or Wittig reactions. Travoprost, the enantio-merically pure isopropyl ester of fluprostenol, is a potent anti-glaucoma drug, for which Chirotech Technology Ltd. has published an interesting synthesis (Fig. 5.102). [229]... 

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). 

Closely related to the Wittig reaction is the Horner-Wadsworth-Emmons reaction, where a stabilized phosphonate carbanion reacts with an aldehyde or ketone to yield an olefin. 

Purpose. The conditions under which the Wittig reaction is carried out are investigated. The Wittig reaction involves the reaction of a phosphorus ylide (Experiments [19A] and [19C]) with an aldehyde or ketone, and is used extensively in organic synthesis to synthesize aUcenes. The use of the Horner-Wadsworth-Emmons modified Wittig reaction between an aldehyde and a phosphonate ester is investigated (Experiments [19B] and [19D]) using phase-transfer catalysis. 

The use of the phosphonate ester (Homer-Wadsworth-Emmons reaction) allows much easier separation of the product alkene, since the sodium phosphate byproduct is water soluble the byproduct of fhe Wiffig reaction, tri-phenylphosphine oxide, is not water soluble. In the Horner-Wadsworth-Emmons modification, a conjugated, or electron-withdrawing, substituent (such as a phenyl or carbonyl group) on the nucleophilic carbon is used to assist in the stabilization of the carbanion. This modification (Experiment [19B]) maybe used as an alternative to Experiment [19A] for the preparation of (E)-stilbene. The "instant-ylide" Wittig reaction yields predominantly the E isomer of... 

---