Wittig reaction Wadsworth-Emmons modification

THE HORNER-EMMONS OR WADSWORTH-EMMONS MODIFICATION OF THE WITTIG REACTION... 

Step 1 (3-keto phosphonates often are used for olefmation of ketones (Horner-Wadsworth-Emmons modification of the Wittig reaction). Steps 2 + 3 The cuprate-mediated 1,4-addition and subsequent Lemieux-Johnson oxidation of a vinyl group are excellent procedures for the introduction of the p-formyl group. 

The past year has seen continued interest in the structural nature of phosphorus ylides with the aim of gaining greater insight into their stabilities, electronic distributions and conformations, which ultimately affect the reactivities of these species. However, there have been fewer mechanistic studies of the Wittig reaction itself although several studies into the closely related aza-Wittig and Horner-Wadsworth-Emmons modifications have appeared. 

Tomizawa, K., Watt, D.S., and Lenz, G.R., Use of P-chloropropionaldehyde as an acrolein equivalent in the Wadsworth-Emmons modification of the Wittig reaction. Synthesis, 887, 1985. 

The Horner-Wadsworth-Emmons modification of the Wittig reaction continues to find wide application in contemporary organic synthesis. Two reviews, looking at different aspects of the stereoselectivity of this procedure, have been published. One considers approaches to improve the Z-selectivity of the Horner-Wadsworth-Emmons reaction, and the other the use of heteroatoms to improve the stereoselectivity of the Horner-Wadsworth-Emmons reaction. A combined experimental and computational study of the selectivity of the Horner-Wadsworth-Emmons reaction of a series of phosphonoacetates (172) has... 

Similarly, 29 can be formed by the Homer-Wadsworth-Emmons modification of the Wittig reaction via the phosphonate 28 rather than the phosphorus ylide 27. In this case, the iodo compound mixture 26 is treated with trimethyl phosphite. Cyclization requires the use of lithium chloride/Hunig s base, ° and cyclization proceeds smoothly at room temperature in similar yield to the Wittig chemistry. Details of this process with isolation and characterization of the intermediates 26, 27, and 29 can be found in a recently published world patent application." Yields for the conversion of 24 into 27 are -77% overall cyclization yield from 27 to 29 is -85%. 

The use of trialkyl phosphites in the Michaelis-Arbuzov reaction has been so widespread during the decades following its discovery that it is almost impossible to select individual examples worthy of separate comment. Some examples of the preparation of benzylic phosphonic diesters may be noted these are of some interest since they are useful reactants in the Wadsworth-Emmons modification of the Wittig reaction, and are extensively used in the synthesis of alkenes It may also be noted that when the phosphite ester possesses different alkyl groups, some selectivity of reaction is possible. ... 

A widely used variation of the Wittig reaction is the Homer—Wadsworth—Emmons modification. 

Purpose To demonstrate the synthesis of a stilbene by the Horner-Wadsworth-Emmons modification of the Wittig reaction. 

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... 

For a discussion of the Wittig reaction and a list of references, including the mechanism and modifications, see Experiment [19]. The role of the phase-transfer catalyst in the Homer-Wadsworth-Emmons modification of the Wttig reaction is also discussed in some detail in that experiment. 

The Wadsworth-Emmons modification [56] of the Wittig reaction uses the phosphonate esters to form a,p-unsaturated esters in which the ( )-alkene is favored (Eq. 7.33) [57]. In situ alkylation is also possible (Eq. 7.34) [56]. The phosphonoesters are prepared by treating the a-bromoesters with triethyl phosphite (Arbuzov reaction) [58]. The diethyl phosphate by-product is water-soluble and easily removed. 

An important modification to the Wittig reaction is the use of stabilized phosphonate carbanions in olefin synthesis. This reaction, originally discovered by Homer but developed by Wadsworth and Emmons, is used extensively for transformation of a carbonyl... 

Horner-Wadsworth-Emmons (HWE) reaction There is a close relationship between the original Wittig alkenation and its phosphonate ester modification which is known as... 

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 ... 

The Wittig reaction along with its modification (Horner-Emmons-Wadsworth) has been employed to generate a variety of interesting structures. For example, conjugated polyenals have been synthesized as shown in nation (46) <88SC51>. 

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. 

The disadvantages of the Wittig reaction described in Section A led to the development of modified olefination methods based on phosphoryl-stabilized carbanions. The most important modification of the Wittig reaction in the field of carotenoid synthesis is olefination by means of phosphonate carbanions, as introduced by Homer [55] and by Wadsworth and Emmons [56]. 

Because the Wittig reaction is so useful for the preparation of alkenes, chemists have explored several variations of it. One of the most useful of these, known as the Homer-Emmons-Wadsworth modification, uses a phosphonate ester derived from an a-haloester or a ketone to generate the Wittig carbanion. 

The Horner-Emmons-Wadsworth Modification of the Wittig Reaction (Section 16.6)... 

A modification of the above reaction, known as the Wittig-Homer reaction or Homer-Wadsworth-Emmons reaction uses phosphonate esters. Thus, the reaction of ethyl bromoacetate with triphenylphosphite gives the phosphonate ester, which on treatment with base (NaH) and reaction with cyclohexanone... 

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