Homer-Emmons modification Wittig reaction

SCHEME 6.68 The Homer-Emmons modification of the Wittig reaction is a generally useful alternative to the standard Wittig reaction. 

The Homer-Emmons modification is a variation of a Wittig reaction in which a phosphonate-stabilized carbanion in used instead... 

The Homer-Emmons modification uses a phosphonate-stabilized carbanion in a Wittig reaction. This reagent is an anion that is more nucleophilic than the usual Wittig ylide. The byproduct (R0)2P02 is water-soluble and easily separated from the product. These phosphonate-stabilized carbanions are compatible with carbonyl groups (especially esters) in the reagent. 

Widmer-Stoermer synthesis, 244 Willgerodt reaction, 65-66 Kindler modification, 65 Williamson synthesis. 35-37 Wittig reaction, Homer-Emmons modification, 74 Wittig synthesis, 17,20-21 Wolff rearrangement, 94 Wolff-Kishner method, 5,7 Wurtz-Fitiig reaction, 5 Wuitz reaction, 5... 

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... 

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 second chirality source used in the synthesis of aminocyclopropane carboxylic acids was D-glyceraldehyde acetonide, which after Wittig-Homer-Emmons reaction provided the alkenes 61. Treatment with diazomethane and subsequent irradiation at low temperatures alforded the cyclopropanes 62, which were converted into several other derivatives by modification of the side chain (Scheme 11). Notably, the best results were obtained by irradiating in the presence of benzophenone as triplet sensitizer [33, 34]. Following a similar synthetic procedure allocoronamic acid 65 was prepared, which is one of the amino acids that can be processed by plant tissues and promises the possibility to control the enzymatic processes underlying plant growth and fruit ripening [35]. 

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 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]. 

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

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. 

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. 

Also for the Wittig reaction, the product may be formed as a mixture of Z- and ii-isomers, but each of these may be improved by applying appropriate reaction conditions. Studies on modifications on the Homer-Wadsworth-Emmons reaction done by StiU and Gennari [38] and Ando [39] have resulted in improved Z-selective reactions. As of today, these reactions are limited to phosphonate esters. 

A very useful modification of the Wittig reaction involves the reaction of phosphonate-stabilized carbanions with aldehydes or ketones, which is known as the Homer-Wadsworth-Emmons (HWE) reaction [7, 151,152], This reaction was originally described by Homer et al. [153, 154] and further defined by Wadsworth and Emmons [155]. Phosphonate-stabilized carbanions are more nucleophilic and more basic than phosphonium ylides. They are prepared by the addition of suitable bases to the corresponding alkylphosphonates, which are readily accessible through the Michaelis-Arbuzov reaction of trialkyl phosphites with alkyl halides (usually a-halo carbonyl compounds) [143]. In contrast to the Wittig reaction, the HWE reaction yields phosphate salt byproducts that are water-soluble and hence are readily separated from the desired alkene products by simple extraction. 

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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