Horner-Emmons reaction condensation

The synthesis of quadrupolar chromophores has also been achieved from 2,6-DTT-dicarboxaldehyde 117. Push-push (i.e., bis-donor) compound 118 was prepared via a double Wittig reaction carried out under solid-liquid phase transfer conditions. Pull-pull (i.e., bis-acceptor) compounds 119 were obtained from a symmetrical bis-aldehydes via a double Horner-Emmons-Wittig condensation (Scheme 9) <2002SM17, 1999CC2055>. 

Sulfanylalkanoyl amino acids and peptides are prepared by reaction of the (acetyl-sulfanyl)- or (benzoylsulfanyl)alkanoic acids or acid chlorides with a-amino esters or peptide esters, followed by deprotection of the sulfanyl and carboxy groups. 8 101114 16 27 29 For example, the 3-(acetylsulfanyl)alkanoic acids 7 are prepared from the condensation of ethyl (diethoxyphosphoryl) acetate 5 with various aldehydes according to the Horner-Emmons reaction, providing the a, 3-unsaturated ethyl esters 6 (a mixture of Z- and E-isomers, 50 50), followed by saponification of the ethyl esters and Michael addition of thiolacetic acid. The 3-(acetylsulfanyl)alkanoic acids 7 can be coupled with a-amino esters or peptide esters and subsequent hydrolysis of the 3-(acetylsulfanyl) derivatives provides the desired products 8 (Scheme 2). 14 ... 

The synthetic method (a) is the regioselective reduction of an a,/ -unsaturated aldehyde or ketone (Section 5.18.2, p. 798), which is most conveniently effected by the Meerwein-Ponndorf-Verley procedure (Section 5.4.1, p. 520). The further disconnection shown of the a, -carbonyl compound is a retro-aldol condensation (Section 5.18.2, p. 799) however it should be emphasised that other routes to the unsaturated carbonyl compound, such as the Horner-Emmons reaction (Section 5.18.2, p. 799), may also be feasible. 

Thus far, the aldol condensation was presented as a method for adding carbon atoms adjacent to carbonyl groups, and the Friedel-Crafts acylation was presented as useful for the addition of carbon atoms to aromatic rings. In addition to these reactions, the Wittig reaction (Scheme 8.13) and the Horner-Emmons reaction (Scheme 8.14) were... 

The starting materials, frans-3,4-methylenedioxycinnamyl alcohol (61a) and frans-2-methoxy-3,4-methylenedioxycinnamyl alcohol (61b) were prepared from the corresponding benzaldehyde via substituted ethyl cinnamate by means of the Horner-Emmons reaction and lithium aluminium hydride reduction. Condensation of compound (61 a) or (61 b) with compound (47) gave compound (62a) or (62b), respectively, followed by ring closure to afford compound (63a) or (63b). Intramolecular Diels-Alder reaction of compound (6 2) led to the formation of the aromatized compounds as by-product in both cases. Moreover, in the reaction of... 

In another approach to the technical synthesis of the apocarotenoids 286, 287 and 292 [118] the C25-aldehyde 12 -apo-p-caroten-12 -al (293) is the key intermediate. Several ways to synthesize this compound have been developed, applying the Wittig reaction to couple the building blocks. By the reaction of the Cas-aldehyde 293 with the protected Cs-phosphonium salt 294 the Cao-aldehyde is obtained [119,120], and this can be transformed by a base-catalysed aldol condensation with acetone (295) to give the Css-ketone citranaxanthin (292) [121]. Alternatively the C2s-aldehyde 293 can be reacted in a Horner-Emmons reaction with the Cs-phosphonate 296 to give 292 [122] Scheme 61). 

For the synthesis of 36, 6-methylhept-5-en-2-one (49) was selected as starting material. Hydrogenation of 49 in the presence of palladium gave the ketone 50 which, in a Horner-Emmons reaction, was condensed with ethyl diethylphosphonoacetate (51) to give the a,P-unsaturated ester 52. Reduction with LiAlHa and treatment of the resultant alcohol 53 with triphenylphosphine hydrobromide gave the phosphonium salt 54. Wittig reaction with crocetindialdehyde (536) and BuLi resulted in 1,2, r,2 -tetrahydrolycopene (36) in an overall yield of 10% referred to 49 and the C3o-aldehyde 55 as a byproduct [10,11] (Scheme 14). 

The reaction of the ester 51 with MeLi (55) in the presence of trimethylsilyl chloride cannot be performed on a large scale in a reproducibly high yield. For the synthesis of the Ci8-ketone 51 on a large scale, an alternative, a three-step route is used (Scheme 18). First the geranylacetone (52J is coupled in an Horner-Emmons reaction with diethyl cyano-methylphosphonate (4) with NaH as a base. Reduction of the nitrile by DEB AH then gives the aldehyde 56 in 73% yield. Aldol condensation of 56 with acetone (57) in the presence of a... 

The phase transfer Wittig-Horner-Emmons reaction has been used to prepare examples of o, i3-unsaturated sulfides, sulfoxides, and sulfones [19]. Although these reactions are discussed in Sect. 14.3, we have summarized in Table 13.7 the results of transformations according to equation 13.10. Note that this reaction yields sulfur compounds on condensation with aldehydes only if the starting phosphonate is sulfur substituted. 

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. 

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). - ... 

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