Using phosphonate carbanions

Wittig reaction, using dichloromethyl-enetriphenylphosphorane, 45,33 using phosphonate carbanions, 46, 46... 

Scheme 2.17. Carbonyl Oleflnation Using Phosphonate Carbanions...

The Homer synthesis of olefins using phosphonate carbanions has been reviewed. Several careful investigations of the mechanism of the Homer reaction have identified the effects of changing phosphonate, solvent, tern-... 

Intramolecular olefination reactions are possible using phosphonate carbanions because they are relatively stable. This type of cyclization is also possible with Wittig reagents, but it is more facile with phosphonate carbanions. One example is Weinreb s treatment of phosphonate 571 with potassium carbonate and a crown ether to give a 84% yield of 572 in a synthesis of phyllanthine.50... 

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. ... 

Tlie interest in the preparation and use of dithiolium salts in connection with the synthesis of TTF derivatives led to the development of a new uses of heteroaromatic cations in organic synthesis. Based on that, a new carbonyl olefination for the synthesis of numerous heterofulvalenes was developed (77S861). For example, 2-dimethoxyphosphinyl-l,3-benzodithiole was deprotonated with butyllithium in THF at -78°C and the resulting phosphonate carbanion reacted with 9-alkyl-acridones to give the dithia-azafulvalenes of type 45 (78BCJ2674) (Scheme 15). 

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 ... 

Olefination Reactions Involving Phosphonate Anions. An important complement to the Wittig reaction involves the reaction of phosphonate carbanions with carbonyl compounds 253 The alkylphosphonic acid esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are generated by treating alkylphosphonate esters with a base such as sodium hydride, n-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.254... 

Intramolecular condensation of phosphonate carbanions with carbonyl groups carried out under conditions of high dilution have been utilized in macrocycle syntheses. Entries 7 and 8 show macrocyclizations involving the Wadsworth-Emmons reaction. Entries 9 to 11 illustrate the construction of new double bonds in the course of a multistage synthesis. The LiCl/amine conditions are used in Entries 9 and 10. 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

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... 

Phosphonate carbanions are more nucleophilic than phosphonium ylides. Thus, they can be used in condensations with ketones as well as with aldehydes under mild conditions. 

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 carbanion 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. 

F2 is the simplest reagent that can be used as source of electrophilic fluorine. Special equipment is required, and fluorination is not selective. When a 10% mixture of fluorine in nitrogen is passed through a solution of stabilized phosphonate carbanions in MeCN, a mixture of the non-, mono-, and difluorinated derivatives is obtained. After purification, the monofluorophosphonate can be isolated in yields not exceeding 50%. ... 

The use of F-TEDA-BF4 for the fluorination of stabilized phosphonate carbanions is limited by its poor solubility in THF. However, potassium salts of sulfonyl-substituted phosphonates react with F-TEDA-BF4 in a THF-DMF mixture to afford the desired monofluorosulfonylphosphonates in 47-61% yield. - The best result on fluorination of the sodium enolate of diethyl l-(ethoxy-carbonyl)methylphosphonate was obtained using F-TEDA-BF4 in a THF-DMF solvent mixture at room temperature, though product yields were quite poor (17%). ... 

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