Phosphine oxide carbanions

Review.1 This review covers use of phosphonium ylides, phosphoryl carbani-ons, and phosphine oxide carbanions in synthesis with particular emphasis on (Z)-and (E)-selectivities (558 references). 

The structure of lithium coordinated P-carbonyl-phosphonate and -phosphine oxide carbanions has been reviewed.6 6... 

Reports of the use in synthesis of the Wittig reaction, and the related methods involving phosphonate and phosphine oxide carbanions and iminophosphoranes, have, if anything, increased and many of these include useful innovations. New results and speculation on the mechanism of the Wittig reaction continue to be published by groups with well established reputations in the area. 

Examples of phosphine oxide carbanions acting as ligands in organometallic compounds include gold and silver complexes, e.g. (143) and (144). ... 

Warren showed that olefination of ketones and aldehydes, or even esters, with phosphine oxide carbanions allows some control of stereochemistry in the alkene products. Reaction with an aldehyde or ketone generates diastereomeric P-hydroxyphosphine oxide products, which can be isolated and then chromatographically separated. Reaction of 573 with n-butyllithium was followed by addition of 3,4-methylenedioxy-benzaldehyde (574, known as piperonal) to give a 9 1 mixture of 575/576, the syn and anti alcohol, respectively.514 7i,e pyre syn alcohol 575 was isolated in 75% yield by chromatography on silica gel. 

The synthesis of 5-ylidenepyrrol-2(5H)-ones (266) from the reaction of maleimides with stabilised phosphoranes under vigorous conditions has been reported.Attempts to use similar reactions of unstabilised phosphoranes, phosphonate-, or phosphine oxide carbanions led to intractable products or recovered starting materials. The procedure developed in these studies has been applied to the synthesis of pukeleimide A (269) using the formation of the ylidenepyrrolone (268) from the maleimide (267) as a key step. ... 

When the ylide is replaced with a phosphine oxide carbanion, the reaction is referred to as the Horner reaction L. Horner et al, Ber. 91, 61 (1958) idem et ah, ibid. 92,2499 (1959). 

The formation of alkene 2 from phosphine oxide carbanion and aldehydes is referred to as the Homer reaction. When using phosphonate carbanion, the reaction is known as the Homer-Wadsworth-Emmons (HWE) 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). 

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 ... 

Well known carbanionic sigmatropic rearrangements, applied to mixed P and S compounds, regio- and/or stereoselectively lead to new (a-sulfanylalkyl) or P-sulfanylaryl) phosphonates, phosphine oxides, or phosphorodiamidates. In these difunctional compounds, chirality can be either introduced on the phosphorus, on the a-carbon, or on the sulfur atom. 

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 intermediate product 162, formed from the nudeophilic addition of 1,2-alle-nic phosphonate or 1,2-allenic phosphine oxide with allylic alcohol, would also undergo a Claisen rearrangement to form 2-oxo-5-alkenyl phosphonate or phosphine oxide 163 [85], The rearrangement is accelerated by the carbanionic nature of the intermediate 162. For the conjugate addition step, the reaction temperature is crucial since the reaction at 0 °C afforded mainly /i,y-unsaturated product whereas a,/8-unsaturated products were formed at 20 °C. 

A convenient route to trivinylphosphine has been developed by thiol elimination from tris[2-(phenylthio)ethyl]phosphine oxide.56 The reaction mechanism involves a phosphoryl-stabilized carbanion, from which benzene thiolate anion is eliminated. 

At this point it should be noted, that olefination involving reaction of PO-stabilized carbanions like those from phosphonates, phosphinates, phosphine oxides, phos-phonamides or thiophosphonates (Horner reaction 47), Horner-Wadsworth-Emmons reaction48 ) with carbonyl compounds almost exclusively yields ( )-olefins. This olefination is essentially restricted to PO-activated compounds carrying stabilizing groups on the carbanionic C-atom. However, these compounds are more reactive than the corresponding resonance-stabilized ylides. Therefore, this olefination method... 

Unlike the carbanions derived from phosphonate esters, the carbanions of dimethyl methylphosphonate18 and, in some instances phosphine oxides (Homer-Wittig reaction), do not react directly with aldehydes and ketones to give the corresponding alkene.2,3 Rather, the reaction yields an intermediate P-hydroxy derivative that can be isolated and purified to high diastereoisomeric purity. Subsequent reaction then gives the desired alkene with control of stereochemistry (see Schemes 3, 5 and Protocols 7, 8). 

The nature of the substituents on a stabilized phosphonate carbanion is known to influence the stereochemical outcome of their reactions with aldehydes. For example, a bis(2,2,2-trifluoroethyl) substituent reverses the normal preference for (E) alkenes in a sequence referred to as the Still modification of the HWE reaction (see Protocol ll).24 This substituent is thought to favour formation of the (Z)-isomeric alkene by greatly enhancing the rate of the elimination of the phosphine oxide to give the alkene, which then suppresses equilibration to the thermodynamic product. 

Ph), or phosphonic amides (97 R = NMe2 or MC HgO) with sodium in dioxane, or with magnesium activated by anthracene in THF, affords the bis(2-hydroxyaryl)phosphinic acid derivative (or phosphine oxide) (98) following a carbanionic rearrangement. 

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. 

The 1,4-addition reaction of stabilized allylic carbanions with conjugated enones is normally complicated by the ambident reactivity of the carbanion. Clean 7-selective conjugate addition to cyclic enones, however, has been observed with lithiated allylic sulfoxides, phosphine oxides and phosphonates... 

Denmark, S.E., and Marlin, J.E., Carbanion-accelerated Claisen rearrangements. Part 7. Phosphine oxide and phosphonate anion stabilizing groups, J. Org. Chem., 56, 1003, 1991. 

The alkaline hydrolysis of phosphonium salts gives phosphine oxides and hydrocarbons resulting from the most stable carbanions in each case. O Benzyl tris(2-pyridyl)phosphonium bromide (17) undergoes rapid alkaline hydrolysis at room temperature to give good yields of benzylbis(2-pyridyl) phosphine oxide and pyridine. ... 

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