Wittig-Horner-type reactions

Phosphorylated ketenes react with aromatic ortho -hydroxy aldehydes to form coumarins by the Wittig -Horner - type reaction. 

Difluoroalkenes1 (cf., 11, 180). The anion (LDA) of this reagent effects difluoromethylenation of aldehydes or ketones by a Wittig-Horner type reaction. 

The MBH reactions of diethyl vinylphosphonate dates back to 1990, and they present similar reactivities to alkyl acrylates. It was found that diethyl vinylphosphonate can be coupled with various aliphatic aldehydes in the presence of DABCO to give moderate to high yields of the corresponding a-hydroxyalkyl phosphonates 85. However, this approach was not effective for aqueous formaldehyde and polyoxymethylene, and the corresponding a-hydroxymethyl phosphonates 87 can only be obtained through a Wittig Horner-type reaction from tetraethyl methylenediphosphonate 86 and formaldehyde (30% aq.) in the presence of a weak base K2CO3 (6-8 m) (Scheme 1.42). 

The use of a phosphine oxide in a Wittig Horner type reaction is exemplified in Scheme 40 to give norvitamin analogues. ... 

Phospha-Wittig-Horner type reactions are a common occurrence in the literature, and what follows is a listing of some of the most salient papers in the period considered by this review (2011-12). 

A second example of step-growth polycondensations with formation of the ole-finic double-bond are Wittig- and Wittig-Horner-type condensations. The Wittig-type polycondensations involve AA/BB-type reactions of aromatic bisal-dehydes with bisphosphonium ylides [99,100] with formation of PPV derivatives (75) and lead to products of only moderate molecular weight (DP 10-20). 

An intramolecular cycloaddition also occurred with 3-ylidenepiperazine-2,5-diones such as 124 or 125, obtained by Wittig-Horner-Emmons reaction from phosphonate 121 and aldehydes 122 or 123, respectively. The products of the Diels-Alder reaction are the bridged bicyclo[2.2.2]diazaoctane rings 126 and 127 that have been found in biologically active secondary metabolite such as VM55599 and brevianamide A. The different type of structures employed in this case requires a chemoselective reaction in order to produce the expected products as single diastereoisomers after 20 days (Scheme 18) <2001JOC3984>. 

Tetrahydroselenopyran-4-one 100 readily reacts with Wittig-Horner-type reagents (Equation 43) <2002MCL107>. Reactions of this type provide convenient routes to precursors of selenium-containing organic conducting materials (see Section 7.11.8.2). 

Some drawbacks of the precursor routes mentioned above have been overcome by the use of polycondensation- and C-C-bond-coupling reactions. To produce soluble PPV-, poly(thiophene)-, or poly(pyrrol) derivatives for spin coating preparation, various types of transition metal catalyzed reactions, such as the Heck-, Suzuki-, and Sonogashira-reaction, Wittig- and Wittig-Horner-type coupling reactions, or the McMurry- and Knoevenagel-condensation have been utilized. 

HORNER - WADSWORTH - EMMONS Olelination Wittig type reaction of ptwsptionale stabilized carbanions with aldehydes or ketones to form olefins... 

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... 

Syntheses follow a kind of bio-mimetic approach [283, 284] in building up the chain during a sequence of Wittig-type reactions or Horner-Wadsworth-Emmons olefination, adding two carbons to the chain at a time with either methyl- or ethyl-branches. As the final products need to be highly pure (E)-stereoisomers, reaction steps and purification need to be carefully controlled. 

Wittig-Horner olefination. This reaction can be effected with LiCl (I equiv.) and either diisopropylethylamine or DBU (1 equiv.) in CH,CN at room temperature. This variation is particularly useful in reactions with aldehydes or phosphonates that can undergo epimerization or aldol-type reactions under standard conditions (NaH or K,CO,). Yields are usually >80%. The reaction also shows a high (E)-selectivity. Presumably a chelated lithium enolate of the phosphonate is the reactive species. 

The Horner-Wittig-type reaction allowed an efficient synthesis of dimeric 717 and trimeric 718 TTF systems starting from the monoaldehyde 716 (Scheme 106) <20040L1569>. 

Chromans. - 2,4-Diethoxychromans (78) (mainly cis) represent a new type of chroman and have been prepared in high yield from a phenol (but not a deactivated phenol) and malonaldehyde bis(diethyl acetal) in the presence of SnCU they are converted into the benzopyrylium salts (79), in excellent yield, by treatment with perchloric acid. A Wittig-Horner reaction of the chiral phosphoryl ( S)-sulphoxide (81) and the ketone (80) gave the chiral sulphoxide (82), which was cyclized by aqueous alkali to a mixture which contained 22% diastereoisomeric excess of (25 )-chroman (i )-sulphoxide. This was converted, in three steps, into the aldehyde (83), which is a useful synthon for a-tocopherol. ... 

Catalytic behaviors of solid base catalysts for fine chemicals synthesis as well as the fundamental reactions are described. The reactions included are double bond isomerization of olefins, addition of hydrogen and amines to conjugated dienes, dehydration, dehydrogenation, reduction, alkylation, aldol addition and condensation, Wittig-Horner and Knoevenagel reactions, dehydrocyclodimerization, and ring transformation. The characteristic features of different types of solid base catalysts, zeolites, metal oxides, solid superbases and non metal-oxides, are summarized. 

The preparation of the PPV skeleton can be generally classified into two main strategies (i) olefinations methods to prepare the vinylene double bond and (ii) transition-metal-catalyzed single bond formation between the arene and vinylene components. The former includes Wittig-, Wittig-Horner- and Knoevenagel-type condensations, whereas the latter approach was demonstrated via Heck, Stille, Suzuki Miyaura and McMurry coupling reactions (Scheme 7.5). 

Wittig reactions (Equation 3) in non-polar media can be initiated by solid-liquid phase transfer of potassium carbonate or t-butoxide with 18-crown-6. Typical salt-free product distributions (Z-disubstituted alkene predominant) are observed with non-stabilized ylidcs in THF, but they are surprisingly reversed in dichloro-methane solution. -Alkenes usually predominate in both solvents when stabilized ylides are involved. Two-phase Wittig-Horner syntheses of ajS-unsaturated sulphides etc. (Equation 5) are also crown-catalysed, as is the Darzens-type process (Equation 14). ... 

By far the main interest in the reaction of halo [ C] acetates with phosphorus nucleophiles is for the preparation of phosphoryl-stabilized carbanions for use in Wittig and related reactions. The presence of the additional electron-withdrawing ester group provides additional stabilization, significantly modifying the reactivity of the ylide species and the stereochemical course of its reactions. The two phosphorus reagents discussed here include the triphenylphosphonium salt type 158. precursors of Wittig methylenetriphe-nylphosphoranes, and the trialkylphosphonoacetate type 159. applied in the Horner-Wadsworth-Emmons family of reactions . ... 

Bis[(diphenylphosphinoyl)methyl] sulfide was converted to (diphenyl-phosphinoyl)methyl vinyl sulfides and to divinyl sulfides in Horner-Wittig type reactions with one or two equivalent(s) of oxo-compounds (ketones or aldehydes) (Schemes 60 and 61). The three-component reaction of lithium alkylselenolates/alkylthiolates, the diphenylphosphine oxide derivative of a bis(propargyl)ether and an aldehyde afforded 3-oxabicyclo[4.2.0]octa-1(8),5-dienes (Scheme 62). ... 

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