Wittig reaction Homer-Wadsworth-Emmons

Addition reactions such as addition of enolates to carbonyl compounds, photochemical cydoaddition, radical addition and elimination reactions such as dehydration can be carried out in microflow reactors. Addition-elimination reactions such as Wittig reaction, Homer-Wadsworth-Emmons reaction, Baylis-Hillman reaction. 

In addition to the Wittig- und Homer-Wadsworth-Emmons reactions, we know a third alkene-forming reaction between carbonyl and phosphororganic compounds, i.e. the Wittig-Homer reaction. In Section 11.2, you will learn that in the course of this reaction a. syn-elim-ination of Ph2P(=0)0 takes places, i.e. another / elimination of I let1/I let2. 

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

Acylphosphonates are suilable carbonyl substrates for Wittig and Homer-Wadsworth-Emmons reactions, but with certain limitations. 5° These limitations are the result of competing side reactions involving proton iransfer or acylation. Homer-Wadsworth-Emmons reactions fail with... 

The Homer-Wadsworth-Emmons reaction is also a useful option for producing olefins in the solid phase. Supported stabilized phosphonoactates, as they are more acidic than phosphonium salts, can readily give the corresponding ylides with weak bases such as DBU, DIPEA, EtaN. One still has to make sure that these reaction conditions are chemoselective. Both types of reactions, Wittig and Homer-Wadsworth-Emmons, have been successfully used in cyclative and/or functionalizing cleavage. 

SeeNicolaou,K.C. Hartner,M.W. Gunzner,J.L. Nadin, A. LieWgi Ann. Chem. 1997,1283-1301, fOT a review of the Wittig and Homer-Wadsworth-Emmons reactions. 

The temporary presence of a carbon-carbon double bond can be advantageous for creating branches in a molecular skeleton by bond formation. This functionality can be obtained not only by olefin metathesis, but also by any carbonyl olefination reaction (Wittig [24], Homer-Wadsworth-Emmons [25], Peterson, or Julia-Lythgoe [9]) (Scheme 3.14). 

A convenient procedure to effect the Wittig and Homer-Wadsworth-Emmons reactions employing guanidine TBD and MTBD as base promoters was developed. Mild reaction conditions highly efficiently facflitated isolation of the final products (Figurel.5) [38]. Further developments oftheWittigreactionhavebeenreported [39,40]. 

Wittig Reaction Horner Reaction Homer-Wadsworth-Emmons Reaction... 

Trialkyl phosphono[ CJacetates ((EtOlzPl0) CH2 COOR) The use of trialkyl phospho-no[ C] acetates 159 in olefination reactions (Homer-Wadsworth-Emmons or HWE reactions) is generally superior to the use of the related Wittig reagents. The carbanions, generated by a suitable base, are more nucleophilic than the latter, so that they react even with ketones. Furthermore, they often show an improved stereoselectivity. They provide 100% -configured acrylates when they react with linear aldehydes, and ( )-alkenes... 

The Witting reaction has been investigated in aqueous conditions.305 Wittig olefination reactions with stabilized ylides (known as the Wittig-Homer or Homer-Wadsworth-Emmons reaction) are sometimes performed in an organic/water biphase system.306 Very often, a phase-transfer catalyst is used. Recently, the use of water alone as solvent... 

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... 

The (Homer-)Wadsworth-Emmons reaction generally is superior to the Wittig reaction, and has found application in many cases for the synthesis of a,/l-unsaturated esters, a,/l-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 Homer-Wadsworth-Emmons reaction represents a methodologically more important and more commonly used supplement to the Wittig reaction (cf. Section 11.1.3) than the Wittig-Homer reaction (Section 11.2). 

Alternatives to the standard Wittig reaction have been developed, including the Homer-Wadsworth-Emmons (HWE) reaction which involves the reaction of a phosphonate stabilized carbanion with a carbonyl compound (Scheme 2). These carbanions are generally more reactive than the traditional phosphoranes and they will often react with ketones that are unreactive to stabilized phosphoranes.2 3,8... 

The use of anions derived from a phosphine oxide (132) or a diethyl phosphonate (133) to form al-kenes was originally described by Homer.Although these papers laid the foundations for the use of phosphoryl-stabiliz carbanions for alkene synthesis, it was not until Wadsworth and Emmons published a more detailed account of the general applicability of the reaction that phosphonates bet e widely used. Since the work of Wadsworth and Emmons was significant and crucial to the acceptance of this methodology, the reaction of a phosphonate caibanion with a carbonyl derivative to form an alkene is referred to as a Homer-Wadsworth-Emmons reaction (abbreviated HWE). The phosphine oxide variation of the Wittig alkenation is called the Homer reaction. 

Whereas the Wittig reaction gives exclusively ( )-isomers, the Homer-Wadsworth-Emmons procedure gives predominantly (Z)-isomers. This result is contrary to expectation because phosphonate carbanions usually give better (/j-spccilicity than phosphoranes. " ... 

Among the different methods for the synthesis of alkenes, none matches the versatility of carbonyl olefination.290 It has been extensively studied since the discovery of the Wittig reaction,291292 and a wide variety of approaches to transform carbonyl compounds into alkenes have been developed. Besides the classical Julia reaction,94 the most generally applicable methods for direct olefination of carbonyl compounds include the Wittig,291,293,294 Homer-Wittig,295,293,296 Homer-Wadsworth-Emmons,297,298,293 Peterson,299 301 Johnson,302 and Julia-Kocienski303,304 reactions. All of these methods involve the addition of a... 

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