Horner-Wadsworth-Emmons condensation reactions

Scheme 8 summarizes the introduction of the missing carbon atoms and the diastereoselective epoxidation of the C /C double bond using a Sharpless asymmetric epoxidation (SAE) of the allylic alcohol 64. The primary alcohol 62 was converted into the aldehyde 63 which served as the starting material for a Horner-Wadsworth-Emmons (HWE) reaction to afford an E-configured tri-substituted double bond. The next steps introduced the sulfone moiety via a Mukaiyama redox condensation and a subsequent sulfide to sulfone oxidation. The sequence toward the allylic alcohol 64 was com-... 

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... 

Cyclopropanation, Horner-Wadsworth Emmons Reaction, and Darzens Condensation Although induction in the cyclopropanation of alkenes was reported early, this work was disputed [49]. Other reports of cyclopropanations have yielded, at best, low asymmetric inductions [llh,50]. The first example of a catalytic asymmetric Horner-Wadsworth Emmons reaction, which is promoted by a chiral quaternary ammonium salt, was reported recently by the Shioiri group (Scheme 10.10) [51]. The reaction of the prochiral ketone 74 gives optically active a,P-unsaturated ester 76 with 57% ee. 

The first example of a catalytic asymmetric Horner-Wadsworth-Emmons reaction was recently reported by Arai et al. [78]. It is based on the use of a chiral quaternary ammonium salt as a phase-transfer catalyst, 78, derived from cinchonine. Catalytic amounts (20 mol%) of organocatalyst 78 were initially used in the Homer-Wadsworth-Emmons reaction of ketone 75a with a variety of phospho-nates as a model reaction. The condensation products of type 77 were obtained in widely varying yields (from 15 to 89%) and the enantioselectivity of the product was low to moderate (< 43%). Although yields were usually low for methyl and ethyl phosphonates the best enantioselectivity was observed for these substrates (43 and 38% ee, respectively). In contrast higher yields were obtained with phosphonates with sterically more demanding ester groups, e.g. tert-butyl, but ee values were much lower. An overview of this reaction and the effect of the ester functionality is given in Scheme 13.40. 

Horner-Wadsworth-Emmons reactions are C—C-forming condensation reactions between the Li, Na, or K salt of a /J-keto- or an -(alkoxycarbonyl)phosphonic acid dialkyl ester and a carbonyl compound (cf. Figure 4.41). These reactions furnish a,f)-unsaturated ketones or a j8-unsaturated esters, respectively, as the desired products and a phosphoric acid diester anion as a water-soluble by-product. In general, starting from aldehydes, the desired compounds are produced fraus-selectively or in the case of olefins with trisubstituted C—C double bonds -selectively. 

Condensations between aldehydes and metallated phosphonic acid dialkyl esters other than those mentioned previously are also referred to as Horner-Wadsworth-Emmons reactions. Nevertheless, in these esters, too, the carbanionic center carries a substituent with a M effect, for example, an alkenyl group, a polyene or a C=N group. The Horner-Wadsworth-Emmons reactions of these reagents are also stereoselective and form the new C—C double bond fraus-selectively. 

Starting from (+)-diethyl tartrate (2), bromobutenolide 18 was obtained in nine steps. Three of the four C=C double bonds were built up using a Wittig reaction (11—>12), an Ando- y Q Horner-Wadsworth-Emmons reaction (13— 15) and (3-elimination (16 18). From (-)-actinol (3) stannane 23 and sulfone 24 were synthesized in 9 and 13 steps, respectively. Their common intermediate, alkyne 22, was synthesized using methoxycarbonylation. Sharpless asymmetric epoxidation and Ci-elongation with lithio trimethylsilyldiazomethane. Stannane 23 was obtained upon hydrostannylation and TBS deprotection. Sulfone 24 was obtained after addition to methyl tetrolate, reduction, Mukaiyama redox condensation, acetylation and catalytic oxidation. 

The first part of this chapter deals with the effects of high pressure on cycloaddition reactions, particularly the Diels-Alder reaction, which is the most important cycloaddition reaction. The second part will illustrate applications of pressure to nucleophilic substitutions, condensations and other reactions (miscellaneous reactions), such as Mannich, Heck, ene, SeAr, Wittig, Horner-Wadsworth Emmons and multicomponent Strecker reactions. 

An imine-enamine annulation has been used in the synthesis of the indoloquinolizidine alkaloid ( )-deplancheine.52 The annulation of dialkyl (1-alkoxycarbonyl)vinylphosphonates via a Horner-Wadsworth-Emmons reaction has been developed in the synthesis of [3.3.0] fused pyrazolid-inones from monocyclic pyrazolidinones. - Treannent of diethyl l-(ethoxycarbonyl)vinylphos-phonate in excess (2 eq) with imide anions such as phthalimide, maleimide, and succinimide successfully produces the corresponding six-membered fused heterocycles. Similarly, synthesis of functionalized cyclohexenylphosphonates is achieved by condensation of diethyl l-(ethoxycar-bonyl)vinylphosphonate (2 eq) with cyclopentanone enolates (Scheme 8.29). - ... 

Two sulfone-based nucleoside diphosphate isosters (71a,b) has been synthesised and reported by Gervay-Hague to be inhibitors of Neisseria meningitidis CMP-sialic acid synthetase, which is a key enzyme in the biosynthesis of capsular polysaccharides required for bacterial infection. The synthetic methodology includes a condensation reaction of the nucleoside aldehydes with bisphosphonate Horner-Wadsworth-Emmons reagents (Scheme 4). The deprotection sequence was crucial for the appropriate completion of the synthetic targets. 

Universal methods for coupling of the synthetic building blocks are the Wittig reaction, the Horner-Wadsworth-Emmons reaction, the sulfone coupling by Julia s procedure, the enol ether condensation (Miiller-Cunradi-Pieroh reaction), and the Saucy-Marbet rearrangement. Since in very many cases mixtures... 

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]. 

AB ABCE ABCDE - ABCDEF W-G aldehyde (-)-Strychnine] (27) After his racemic synthesis of strychnine (26), Kuehne also achieved an enantioselective synthesis of (—)-strychnine (Scheme 9). To avoid the low yield conversion of isostrychnine to strychnine, the second approach was directed to the W-G aldehyde. Starting from L-tryptophan methyl ester (86), the cyclization precursor 87 was prepared in seven steps in a similar way as in the previous racemic synthesis. The domino condensation-electrocyclization reaction of 87 with dienal 88 proceeded with quite high diastereoselectivity (>95% de) [AB ABCE, C7 quaternary center] (85). After conversion of the tetracyclic compound 89 to tosylate 92, removal of the benzyl group resulted in the clean formation of the D ring [ABCE ABCDE ]. Unlike in the first synthesis, introduction of the hydroxyethylidene side chain by a Horner-Wadsworth-Emmons reaction of ketone 93 proceeded with high stereoselectivity (E Z = 17 1). Einally, the E isomer 94E was converted to (-)-strychnine via the W-G aldehyde (50). 

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