Phosphines Wittig reaction

The phosphorus ylides of the Wittig reaction can be replaced by trimethylsilylmethyl-carbanions (Peterson reaction). These silylated carbanions add to carbonyl groups and can easily be eliminated with base to give olefins. The only by-products are volatile silanols. They are more easily removed than the phosphine oxides or phosphates of the more conventional Wittig or Homer reactions (D.J. Peterson, 1968). 

Another very important reaction initially involving nucleophilic attack on an aldehyde carbonyl is the Wittig reaction. An yUd adds to the carbonyl forming a betaine intermediate which then decomposes to produce an olefin and a tertiary phosphine oxide. 

A useful apphcation of phosphines for replacing a carbonyl function with a carbon—carbon double bond is the Wittig reaction (91). A tertiary phosphine, usually triphenylphosphine, treated with the appropriate alkyl halide which must include at least one a-hydrogen, yields the quaternary salt [1779A9-3] which is then dehydrohalogenated to form the Wittig reagent, methylenetriphenylphosphorane [19943-09-5] an yhde. 

Much better known are the fluonnatedphosphoranes, which have been widely used m the Wittig reaction for the preparation of fluoroolefms Difluoromethylena tion reactions have been effected by using a variety of conditions Treatment of dibromodifluoromethane with two equivalents of tns(dimethylammo)phosphine m carefully dried tnglyme yields a solution of bromodifluoromethylphosphonium broomide, which very effectively converts ketones to difluoromethylene derivatives A more sensitive reagent is prepared by the addihon of two equivalents of the phosphine to the reaction mixture of fluorohalomethane and a carbonyl compound [39, 40] (equation 40) (Table 14)... 

The reaction of an alkylidene phosphorane 1 (i.e. a phosphorus ylide) with an aldehyde or ketone 2 to yield an alkene 3 (i.e. an olefin) and a phosphine oxide 4, is called the Wittig reaction or Wittig olefination reaction. ... 

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 ... 

In the Wittig reaction an aldehyde or ketone is treated with a phosphorus ylid (also called a phosphorane) to give an alkene. Phosphorus ylids are usually prepared by treatment of a phosphonium salt with a base, and phosphonium salts are usually prepared from the phosphine and an alkyl halide (10-44) ... 

The overall sequence of three steps may be called the Wittig reaction, or only the final step. Phosphonium salts are also prepared by addition of phosphines to Michael alkenes (hke 15-8) and in other ways. The phosphonium salts are most often converted to the ylids by treatment with a strong base such as butyllithium, sodium amide, sodium hydride, or a sodium alkoxide, though weaker bases can be used if... 

The reaction takes place probably by a kind of inverse Wittig reaction , corresponding to the thermal dissociation of an oxaphosphetene resulting from a [2+2] cycloaddition between the phosphine oxide and the activated acetylenic compounds (Scheme 2) [11,12]. 

More recently, P-cored derivative (116) was prepared from a straightforward combination of a Heck coupling, to afford an intermediate functionalised stil-bene phosphine oxide (114),a Horner-Wittig reaction yielding the phosphine oxide (115), and finally trichlorosilane reduction (Scheme 31) [89]. Using similar strategies, both the valence isoelectronic N- (117) and C- (118) cored dendrimers have been prepared (Scheme 31). 

Wittig reactions are versatile and useful for preparing alkenes, under mild conditions, where the position of the double bond is known unambiguously. The reaction involves the facile formation of a phosphonium salt from an alkyl halide and a phosphine. In the presence of base this loses HX to form an ylide (Scheme 1.15). This highly polar ylide reacts with a carbonyl compound to give an alkene and a stoichiometric amount of a phosphine oxide, usually triphenylphosphine oxide. 

There are related reactions involving phosphonate esters or phosphines oxides. These reactions differ from the Wittig reaction in that they involve anions formed by deprotonation. In the case of the phosphonate esters, a second EWG substituent is usually present. 

Carbanions derived from phosphine oxides also add to carbonyl compounds. The adducts are stable but undergo elimination to form alkene on heating with a base such as sodium hydride. This reaction is known as the Horner-Wittig reaction.268... 

The chloromethyl derivatives of 1 and 2 can be converted to the corresponding phosphonium salts by treatment with triphenyl-phosphine.19 A subsequent phase transfer catalysed Wittig reaction of these salts with formaldehyde introduced pendant vinyl groups. 

The use of water-soluble reagents and catalysts allows reactions to be performed in aqueous buffered solutions. PEG-supported triarylphos-phine has been used in a Wittig reaction under mildly basic aqueous conditions (Eq. 8.115). The PEG-supported phosphine oxide byproduct can be easily recovered and reduced by alane to regenerate the starting reagent for reuse.312 The aqueous Wittig reaction has also been used in... 

Aminoethylidenehydrazones 161 react with triphenyl phosphine to give the azinoiminophosphorane intermediates 162 which cyclize via an aza-Wittig reaction with benzaldehydes to give the corresponding 1,2,4-triazoles 163a-j (Scheme 14 and Table 32) <2002JHC845>. 

Replacement of the triphenyl group by trialkyl groups increases the trans-selectivity, but increase in the bulk of the customary phenyl groups can increase cis-selectivity. Tris(o,o -difluorophenyl)phosphine (m.p. 125-127°) is recommended as a replacement for triphenylphosphine in dr-selective Wittig reactions, particularly of aromatic and a,(l-unsaturated aldehydes. 

The Wittig reaction consists in the replacement of carbonyl oxygen of aldehydes and ketones by a methylene group with the aid of phosphine-methylenes resulting in the formation of cis or trans olefines. The reaction proceeds through the nucleophilic addition of Wittig reagent (phosphine methylene) across the > C = O bond and formation of an intermediate cyclic. 

The lluorous biphasic technique has also been applied to the Wittig reaction, one of the most effective methodologies for the production of C=C double bonds [13] (Scheme 10.11). One of the major drawbacks of this reaction is the separation of the alkene from the phosphine oxide by-product. This is commonly achieved via recrystallization or column chromatography, but recently it has been shown... 

Formate esters behave as typical carbonyl compounds in reactions with a number of ylides, eliminating phosphine oxide and forming vinyl ethers, e.g. (33).35 Stabilized phosphoranes are able to condense with the carbonyl group of cyclic thioanhydrides (34).38 Quinoline derivatives, e.g. (35), are obtained from the condensation of dicar-boalkoxy-ylides with isocyanates.37 Benzoyl isothiocyanates and keto-phosphoranes give quantitative yields of (36), which are unreactive in Wittig reactions but can be readily oxidized by selenous acid.38 The products obtained from reactions (Scheme 9) with the triazolinedione (37) depend upon the stability of the ylide used.39... 

The attack of nucleophiles on unsaturated ligands or functional groups bonded to metallic centers, exemplified in Scheme 9 (reaction of metallic carbenes with phosphines or pyridines) or in Scheme 15 (Wittig reaction) can be extended to a wide variety of reagents. Two main groups of reactions can be considered (1) those in which the nucleophile is an ylide and (2) those in which the nucleophile is a phosphine (and less commonly other nucleophiles). Usually these reactions give metallated ylides (type III), that is, species in which the ylide substituents are metallic centers. 

The unique feature of the Horner-Wittig reaction is that the addition intermediate can be isolated and purified. This provides a means for control of the stereochemistry of the reaction. It is possible to separate the two diastereomeric adducts in order to prepare the pure alkenes. The elimination process is syn so that the stereochemistry of the alkene depends on the stereochemistry of the adduct. Usually, the anti adduct is the major product, so it is the Z-alkene which is favored. The syn adduct is most easily obtained by reduction of /i-keto phosphine oxides.160... 

Furans having a double bond at position 2 can be obtained by a phosphine-initiated cyclization of enyne ketones in the presence of an aldehyde. The reaction may involve the 1,6-addition of the phosphine toward the enyne, ring closure and Wittig reaction of the ylide with the aldehyde <99TL3753>. 

Supported carbodiimides can be produced via aza-Wittig reactions. The example in Scheme 11 shows the reaction of a benzylic azide with triphenyl-phosphine to give an aminophosphorane.31 This was then coupled with phenylisothiocyanate to give the corresponding carbodiimide. 

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