Horner-Emmons condensation

Sharpless asymmetric dihydroxylation procedure was applied to the synthesis of the side chain of azinomycin A (equation 26)43. Horner-Emmons condensation of phospho-nate 36 with a /J-aziridine substituted acrolein afforded dehydroamino acid diene 37. Treatment of the diene with catalytic amounts of an osmium reagent and dihydroquini-dine (DHQD) p-chlorobenzoate resulted in asymmetric dihydroxylation, producing diol 38. Diol 38 was further converted to the naphthyl ester. 

An efficient and regioselective method for the synthesis of pharmaceutically important intermediates (323) has been developed. It is based on the intramolecular Wadsworth-Horner-Emmons condensation of monocyclic compound (322), which is available by a selective stepwise functionalization of pyrazolidinone (321) (Scheme 64). The overall yield is about 25% <90TL2805>. 

An extremely elegant route to pyrazoles which allows control over all three substituents, involves forming a ring closure precursor by Horner/Emmons condensation of a tosylhydrazone-phosphonate with an aldehyde, which become the 5-substituent intramolecular Michael addition and then loss of toluenesulfinate as the final aromatising step, completes the sequence. 

The C21-C37 segment (183) The construction of the polyene chain from aldehyde 185 involved the use of lithiated phosphonate 127 twice as follows Horner-Emmons condensation generated a , , -triene ester which was reduced and oxidized to aldehyde 208 (Scheme 28). Iteration of this process, including a THP cleavage, generated the desired hydroxy aldehyde 183. 

Acrolein (80) was converted, with ethanol and p-toluenesulphonic acid, into the acetal 81 which was reacted with acetaldehyde (82) in the presence of benzoyl peroxide to give the ketone 83. The Horner-Emmons condensation with ethyl diethylphosphonoacetate 51 gave... 

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>. 

The preparation of 1 started with the addition of lithiated 4 to the enantiomcrically-pure epoxide 5, which was prepared from the racemate using the Jacobsen protocol. Reduction followed by selective protection of the primary alcohol gave the monosilyl ether, which was further protected with MOM chloride to give 7. Pd-mediated oxidation to the methyl ketone followed by condensation with the Horner-Emmons reagent gave the unsaturated ester 8 as an inconsequential mixture of geometric isomers. Oxidation then set the stage for the crucial cyclization. 

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... 

Harrowven, D. C., Bradley, M., Lois Castro, J., Flanagan, S. R. Total syntheses of justicidin B and retrojusticidin B using a tandem Horner-Emmons-Claisen condensation sequence. Tetrahedron Lett. 2001, 42, 6973-6975. 

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). 

More elaborate 4-hydroxy-enals and -enones have been generated in a variety of ways, for example via alkynes or often via epoxides, it being sometimes unecessary to isolate the hydroxy-enone, or via Horner-Wadsworth-Emmons condensation of /3-ketophosphonates with a-acetoxyketones. Acetal thioenol-ether or terminal alkyne can be employed as surrogate for the carbonyl group. Some of these are exemplified below. 

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). 

---