By Wittig-Horner reaction

The anomeric appendage of imino sugars has been exploited to generate mimics of glycoconjugates. An example is reported in Fig. 42 for the synthesis of nojirimycinyl C-(L)-serine 109,73 in which the ozonolysis of the allylic appendage generates the aldehydes 106, on which the aminoacidic moiety was inserted by Wittig-Horner reaction. 

Paquette et al. start with the bis-vinylogation of the same compound 29 [14], by Wittig-Horner reaction, reduction, and oxidation (Scheme 5). For the formation of the C17-C16 bond, the onti-aldol 41 (ds not reported) is obtained by treatment of the aldehyde 39 with the (Z)-boron enolate 40, bearing a dithioketal moiety that is later to be the C51-C54 side chain. 3-Hydroxy-assisted, diastereoselective reduction of the keto group at C15 gives 41, which is converted into intermediate 42 in five more steps. The dethioketalization of 41 is achieved with phenyliodine(m) bis(trifluoroacetate) [16], As in Nicolaou s synthesis, the N12-C13 amide bond is formed first, followed by a low-yielding (21%, even at a concentration of 1 him) macrolactonization to 3. Table 1 summarizes the benchmark data of the two total syntheses of sanglifehrin A (1). 

Swern oxidation of alcohol 15, prepared in Scheme 5, followed by Wittig-Horner reaction of the resulting aldehyde afforded the a,(3-unsaturated ester, which was converted to alcohol 16 in a 3-step sequence. Swern oxidation of 16 and Wittig-Horner reaction of the resulting aldehyde gave conformationally constrained piperidine 17. 

Etemad-Moghadam, G., and Seyden-Penne, J., Stereoselective synthesis of -a-fluoro a,P-unsaturated esters by Wittig-Horner reaction from methyl a-((9,(9-diethylphosphono)-a-fluoroacetate. Comparison with methyl a-(diphenylphosphinyl)-a-fluoroacetate. Bull. Soc. Chim. Fr, 448, 1985. 

A series of Af-(alk-l-enyl) nucleobase compounds has been prepared by Wittig-Horner reaction of phosphine oxides (165)-(167) or the Horner-Wadswor-th-Emmons reaction of the analogous phosphonates (168) and (169). Hor-ner-Wittig reactions have been utilised for the stereoselective synthesis of single... 

General Procedure for the Preparation of the Series 52c (n = 1-4) by Wittig-Horner Reactions (Scheme 11.23 and Table 11.4) [211]... 

Important and widely used variants of the Wittig reaction are based on carbanionic organophosphorus reagents, and are known as the Wadsworth-Emmons reaction, Wittig-Horner reaction or Horner-Wadsworth-Emmons reaction. As first reported by Horner, carbanionic phosphine oxides can be used today carbanions from alkyl phosphonates 13 are most often used. The latter are easily prepared by application of the Arbuzov reaction. The reactive carbanionic species—e.g. 14 —is generated by treatment of the appropriate phosphonate with base, e.g. with sodium hydride ... 

A Michaelis-Arbusov rearrangement followed by a Wittig-Horner reaction is involved in preparation of the distyrylbenzene derivative 11.37, as shown in Scheme 11.15. Precautions must be taken in the first stage to minimise formation of the carcinogenic by-product bis(chloromethyl) ether 11.16. The stilbene bis-ester 11.38 can be made by a similar procedure, or alternatively by the reaction of ethyl acrylate with 4,4 -dibromostilbene in the presence of a palladium-based catalyst (Scheme 11.16), a synthesis that yields the required trans form of the brightener. 

When one of the reacting partners in the Wittig-Horner reaction, either the phosphine oxide or the carbonyl compound, has a double bond, the product is a diene. The Wittig-Horner reaction was utilized by Smith and coworkers in the total synthesis of milbemycin (equation 98)170. They found that when sodium hexamethyldisilazide was employed as a base, the desired E-diene selectivity is high (85%). Some examples from the literature where the Wittig-Horner reaction has been utilized for the construction of E-double bonds present in dienes and polyenes are given in Table 19171. 

In the case of the synthesis of 10,19,19,19-2H4-vitamin A, the most useful for biological studies, three deuterium atoms were incorporated into /i-ionone 30, in >98% by deuterium exchange with excess D2O in the presence of Na02H (and pyridine). The tri-deuteriated 30, utilized in Wittig-Horner reaction with dideuterio triethyl phosphonate, provided tetradeuteriated ethyl /J-ionilidene acetate 31 with more than 98% 2H4 (by NMR). No deuterium loss in the subsequent synthetic steps was observed as evidenced by MS and NMR analysis. 

Vinyl phosphonates have been used in the construction of valerenic acid terpenoids 169 (Scheme 42).101 Both five-and six-membered rings can be formed via the vinyl phosphonate Alder-ene reaction which can be catalyzed by a variety of Lewis acids. The resulting structures 167 are suitable for Wittig-Horner reaction to give diene 168. Subsequent reactions access valerenic acid terpenoids 169. The chirality of the carbon bearing the phosphonate and ester is transferred, but is subsequently lost in the Wittig-Horner step. 

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>. 

The diphenylamino-substituted PPV107, with solubilizing alkoxy groups, was synthesized by Shi and Zheng [150] via Wittig-Horner reaction (Chart 2.23). Its PL (555 nm) is very similar to that of diamino-PPV 64 and dialkoxy-PPV 14 homopolymers. The PLQY is rather high in solution (80%), but it drops to only 8% in films. Consequently, only a moderate EL efficiency of 0.6cd/A was obtained with this material (device ITO/PEDOT/107/Mg/Al) [150]. Almost simultaneously, Kido and coworkers [151] reported a similar diphenylamino-substituted PPV copolymer 108, which affords very efficient PLEDs. The device ITO/PEDOT/108/Ca/Al... 

Only low yields (10%) of coumarin were obtained by the intramolecular Wittig-Horner reaction of 2-(diethoxyphos-phorylacetoxy)benzaldehyde using (35) as an EGB (formed ex situ in MeCN) [98]. 

An investigation of the Wittig-Horner reaction taking place under sonochemical irradiation and catalyzed by the activated Ba(OH)2 showed that the process could be markedly improved. The sonochemical process increased the reaction rate over... 

Preparation of 18,18,18-trifluororetinal required synthesis of trifluorocyclocitral as precursor. For this purpose, the 1,4-addition of a cuprate (prepared from an a>-bromo-trifluoromethylcarbinol) onto a vinylidene phosphonate was performed. The alcohol moiety is then deprotected and oxidized into ketone. A further intramolecular Wittig-Horner reaction, followed by reduction, led to trifluorocyclocitral. 18,18,18-Trifluororetinal is then easily obtained from this compound (Figure 4.25). ... 

Some syntheses of 2- or 3-fluoro-2,3-dideoxyfuranoses have been described starting from l- or D-glyceraldehyde or from other acyclic precursors. They involve a Wittig-Horner reaction, followed by a Sharpless epoxidation (Figure... 

Ally vinyl ethers. Enol ethers of aldehydes ean be obtained in moderate to high yield by a Wittig Horner reaction of aliphatic ketones with I and an alcohol in the presence of a base (equation I).2... 

Various methods have been used to lengthen a carbon side chain, in the syntheses of quinuclidyl-3-acetic acid (113) (Scheme 1). The lowest yield is in the sodiomalonic ester synthesis (13.4% ).125 Much better results are afforded by the Reformatsky reaction (40%)125 and Knoevenagel condensation (65-70%).129 The best yield (nearly quantitative) may be obtained by application of the Wittig-Horner reaction.155... 

When a mixture of finely powdered 1 1 inclusion compound of (-)-l and 4-methyl-cyclohexanone 2a (1.5 g) and (carbethoxymethyl)triphenylphosphorane 3 (2.59 g) was kept at 70 °C, the Wittig-Horner reaction was completed within 4 h. To the reaction mixture was added ether-petroleum (1 1), and the precipitated solid (triphe-nylphosphine oxide and excess 3) was removed by filtration. The crude product left after evaporation of die solvent of the filtrate was distilled in vacuo to give (-)-4-methyl-l-(carbethoxymediylene)cyclohexane 4 of 42.3% ee in 73% yield. 

Butenolides. The fmnal steps in a synthesis of jolkinolide E (4) involve formation of the butenolide ring by reaction of the a-hydroxy ketone 1 with the mixed anhydride of trichloroacetic acid amd a-(diethylphosphono)propionic acid (2) with catalysis by DMAP. The ester 3 undergoes an intramolecular Wittig-Horner reaction in the presence of NaH to give 4. ... 

Alfytic tertiary amines The reagent serves as a starting material for a regio- and stereospecific synthesis of allylic tertiary amines by the Wittig-Horner reaction shown in the example. 

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