Horner-Wadsworth-Emmons condition

The starting material for iloprost is the enantiomerically pure Corey lactone, which is treated with the lithium salt of ethyl acetate. After oxidation, treatment with l,5-diazabicyclo[4.3.0]non-5-ene (DBN) leads to an exceptionally interesting rearrangement. Presumed cleavage of the cyclic ether generates an enolate, which adds to the cyclopentenone in a Michael reaction. Decarbethoxylation is achieved with l,5-diazabicyclo[2.2.2]octane (DABCO), and the w-chain is constructed under Horner-Wadsworth-Emmons conditions. The subsequent reduction leads to a mixture of allyl alcohols, which can be purified by chromatography, and the alcohol from the less polar product then be released by trans-esterification. Both alcohol functions are then protected as THP-ethers. The... 

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... 

Pyridylidenehydantoins such as 139, obtained from pyridinecarbaldehydes by Horner-Wadsworth-Emmons reactions, are cyclized under acidic conditions to tricycles of the type 140 (Scheme 39) <2004TL553>. Similar benzannulated ring systems can be prepared by the reaction of 2-benzimidazolylacetonitriles and, for example, 2-chloronicotinic esters or 2-chloronicotinamides under basic conditions (Equation 32) <1996JHC1147, 1997JHC397>. 

S. Arai, S. Hamaguchi, T. Shioiri, Catalytic Asymmetric Horner-Wadsworth-Emmons Reaction under Phase-Transfer-Catalyzed Conditions , Tetrahedron Lett 1998, 39,2997-3000. 

The enoates 17 were obtained in good yield and diastereoselectivity by subjecting the crude hydroformylation products 6 to Horner-Wadsworth-Emmons olefination conditions (HWE). Reaction of enoates 17 with dialkyl Gilman cuprates gave the anti 1,4-addition... 

In the example shown the deprotonation of the phosphonate can be achieved under much milder conditions than with the usually employed sodium hydride, which by the way also applies to the standard Horner-Wadsworth-Emmons reagents. Incorporation of the two doubly bound oxygen atoms of the reagent A into sodium chelate B does the trick. Being a cation, B is much more acidic than A and can thus already be deprotonated by an amidine. 

Standard Wittig/Horner-Wadsworth-Emmons reaction conditions (Table 8, entries 25, 26) [477] The method presented here yields predominantly (E)-alkenes. 

The final steps of the synthesis are summarized in Scheme 34. After a sequence of protection-reduction-oxydation, 171 was transformed to aldehyde 172 which was directly submitted to a Horner-Wadsworth-Emmons homologation with the requisite stabilized reagent K under Ando conditions [115] to give the corresponding a,(3-unsaturated ester 173 (Z/E > 95/5) in 84% yield. Treatment of ester 173 with 1% HC1, EtOH led to (-)-pironetin after purification (89% yield). 

The Fukuyama indole synthesis involves the intramolecular radical cyclization of 2-alkenylisocyanides, the availability of which often limits the utility of this process. In order to access a wider variety of such substrates, the author prepared the versatile Horner-Wadsworth-Emmons reagent 131 using the Pudovik reaction <01SL1403>. Reaction of 131 with a variety of aldehydes thus provides a convenient and general route to diverse alkenyl precursors 132. Additionally, instead of the standard radical conditions using tri-n-butyltin hydride, Fukuyama now finds that excess thiols arc quite effective for inducing cycliz.ation, whereupon desulfurization of the indoles 133 can be effected with Raney-Ni if desired. 

At the same time as new applications of ionic liquids are discovered on almost a daily basis, limitations of these reaction media are also uncovered. While studying the Morita-Baylis-Hillman reaction in ionic liquids, Aggarwal observed that [bmim][Cl] was deprotonated by the weak base present in the reaction mixture, leading, after reaction with benzaldehyde, to salt 111 (Scheme 49). Deprotonation of imidazolium salts with strong bases (KCyBu or NaH) is well known, providing, for example, an easy route to Pd-carbene complexes (Section 2.3.5.1). However, this observation limits the use of imidazolium-based ionic liquids even in weakly basic conditions, where they can react with electrophiles. It also explains previous works reporting low yields for reactions performed in these conditions, such as the Horner-Wadsworth-Emmons reaction in [emimlCPFe] or [emim][BF4]. ... 

Reactions of lithiated ethyl 6-(dimethoxyphosphoryl)cyclohex-l-enecarboxylate with aliphatic, aromatic, and unsaturated aldehydes have been studied and determined to proceed with a or 5 regioselectivity. Such an unusual regioselectivity resulted from the contribution of two allylic carbanions one, stabilized by the phosphonate moiety and the other stabilized by the carboethoxy group. The course of the reaction depends mainly on the stmcture of the aldehyde and the reaction conditions. The products of Horner-Wadsworth-Emmons reaction were formed under kinetic conditions, whereas the 5-adducts were obtained as thermodynamic products. 

The Wittig synthesis of alkenes and variations of it, such as the Horner-Wadsworth-Emmons reaction, are now regarded as among the classic reactions of organic chemistry. Such reactions are of enormous importance because they produce alkenes of predictable structure under mild conditions. In performing some of the experiments in this chapter, you may be executing a functional group transformation that earned its discoverer a Nobel Prize in Chemistry (Sec. 18.2). 

Reactions with Aldehydes and Ketones. The carbanion derived from the treatment of (Me0)2P(0)CH(SMe)2 with a base reacts with cyclic and acyclic, aliphatic and aromatic aldehydes and ketones in a Horner—Wadsworth—Emmons reaction to give ketene 5,5-thioacetals in high yields " (eq 2 ). The carbanion is generated using either butyllithium in THE at —78 °C > or, less commonly, sodium hydride in DME. Alternatively, with aromatic aldehydes the reaction may be performed under two-phase conditions using benzyltriethylammonium chloride (TEBA) as a phase-transfer catalyst. ... 

Purpose. The conditions under which the Wittig reaction is carried out are investigated. The Wittig reaction involves the reaction of a phosphorus ylide (Experiments [19A] and [19C]) with an aldehyde or ketone, and is used extensively in organic synthesis to synthesize aUcenes. The use of the Horner-Wadsworth-Emmons modified Wittig reaction between an aldehyde and a phosphonate ester is investigated (Experiments [19B] and [19D]) using phase-transfer catalysis. 

Formation of C-N bond has raised of interest in the scientific community in the last 10 years. In this context, the formation of enamides is a valuable protocol. In addition to conventional approaches that include condensation of amides and aldehydes, addition of amides to alkynes, acylation of imines, Curtius rearrangement of a,jS-unsaturated acyl azides, amide Peterson olefination, and Wittig and Horner-Wadsworth-Emmons reactions, several transition metal-catalyzed methods have been developed that allow the synthesis of enamides.Inspired by the analogous arylation of amines catalyzed by palladium or copper complexes (Buchwald-Hartwig reaction), a new approach for the synthesis of enamides has been published recently, which allows to prepare enamides from readily available starting materials (amides and vinyl halides) proceeding under very mild conditions. Thus, we decided to test the Porco-Buchwald amidation of vinyl halides in our synthesis [144-146]. 

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