Horner-Wittig olefination

The synthesis in Scheme 13.21 starts with a lactone that is available in enantiomer-ically pure form. It was first subjected to an enolate alkylation that was stereocontrolled by the convex shape of the cis ring junction (Step A). A stereospecific Pd-mediated allylic substitution followed by LiAlH4 reduction generated the first key intermediate (Step B). This compound was oxidized with NaI04, converted to the methyl ester, and subjected to a base-catalyzed conjugation. After oxidation of the primary alcohol to an aldehyde, a Wittig-Horner olefination completed the side chain. 

Scheme 7.9. Domino reduction/Wittig-Horner olefination process of aspartates.

In a third microreactor, the anion of 4-ferf-butyl l-ethyl-2-(diethox-yphosphoryl)succinate was prepared in situ using sodium ethoxide 237 (in EtOH) and the Wittig-Horner olefination with benzaldehyde 116 performed using a residence time of 47 min to afford (E)-ferf-butyl-l-ethyl-2-benzylidenesuccinate 238 in excellent selectivity (89% yield). In a fourth reactor, the acid-catalyzed (TFA 239) ferf-butyl ester deprotection was achieved using a residence time of 5 min at 34 °C and employing DCM as the reaction solvent to afford (E)-3-(ethoxycarbonyl)-4-phenylbut-3-enoic acid 246 in 82% yield. The deprotection was subsequently followed by a Friedel-Crafts acylation, using triethylamine 14 and acetic anhydride 37, to afford 4-acetoxy-naphthalene-2-carboxylic acid ethyl ester 241 in quantitative yield when conducted at 130 °C (residence time = 47 min). 

Wettability-based microvalve, 32-33, 32f Wittig-Horner olefination, 115,182... 

A similar intramolecular Wittig-Horner reaction provides a key 5,6-dihydropyran-2-one 880 intermediate during synthetic studies towards leinamycin. The choice of base, lithium tert-butylate (/-BuOLi), is vital for the high yield observed due to the importance of the lithium cation for smooth deprotonation of the phosphonoacetate, the first time this base is documented during a Wittig-Horner olefination (Equation 353) <2005T7481>. 

A more convenient procedure without the use of HMPT leading to diethyl 1,2-epoxyalkanephosphonates has been reported by P. Savignac and P. Coutrot41 who also showed that a Wittig-Horner olefination takes place when diethyl dihalo-methyllithiumphosphonates are reacted with carbonyl compounds, as shown by... 

Wittig-Horner olefination. This reaction can be effected with LiCl (I equiv.) and either diisopropylethylamine or DBU (1 equiv.) in CH,CN at room temperature. This variation is particularly useful in reactions with aldehydes or phosphonates that can undergo epimerization or aldol-type reactions under standard conditions (NaH or K,CO,). Yields are usually >80%. The reaction also shows a high (E)-selectivity. Presumably a chelated lithium enolate of the phosphonate is the reactive species. 

Since a synthetic route to heterocyclic calcitriol derivatives was still lacking, explorative research had to be carried out. The vitamin D aldehyde 1 was prepared according to the Leo protocol [192] followed by a photosensitized isomerization of the triene unit in seven steps (Scheme 10.2). Wittig-Horner olefination selectively yielded the E-double bond configuration of the Weinreb amide 2. Reduction with diisobutylaluminum hydride gave the unsaturated aldehyde 3 without any evidence for overreduction. This aldehyde could serve as a valuable intermediate for further elaboration of the side-chain [194],... 

Other reactions evaluated by the authors included Wittig-Horner olefination and a series of ring-closing metathesis (RCM) reactions, employing Grubb s II catalyst. In all cases, a reduction in power consumption, increase in yield, and reduction in reaction time were obtained as a result of employing microwave-assisted continuous flow reactions [33],... 

C2-homologizati on of sugars with, 264-265 Acetamide, JV-bromo- (AcNHBr, NBA) bromohydrination with, 275-276, 287 Acetaminophen (= paracetamol), 301 Acetate, piperidinium cat. for aldol add., 82 —, sodium a-epimerization of ketones, 277 opening of oxiranes, 282 Acetic acid, anhydride (AcfO) protection with. See Protection Pummerer rearr. with, 51, 265 —, esters (See also Protection of hydroxy groups) C-H acidity, 10 1-methylethenyi ester pr., 174 transenolization, 58 —, bromo-, esters pr., 179 a2-synthon, 19, 65, 309 d2-synthon, 19, 301 —, chloro-, esters pr., 179 hydantoins from, 308 —, cyano-, esters pr., 177 pyrrolines from, 298 —, (dialkoxyphosphinyl)-, esters pr 188 Wittig-Horner olefinations, 267, 282 —, diazo-, ethyl ester pr, 176, 178 cyclopropanes from, 74—75 —, dichloro- deblocking of pixyl ethers, 342 —, hydroxy-, esters pr., 176 —, hydroxyphenyl-, (S)- (l-mandelic acid) ... 

A new route to the fused tetrahydropyridines (222) has been described by Minami et al. which involves initial nucleophilic addition of the imide anions (220) to the vinylphosphonate (219), to give the phosphonate anion (221). Subsequent addition of a further molecule of (219), followed by an intramolecular Wittig-Horner olefination gives the products (222), generally in high yields. ... 

The Wittig-Horner olefination of the aldehyde 28 provided alkenes 29 which were subjected to radical cyclization leading to benzofused tricyclic j6-lactams 30, obtained as single diastereomers (Scheme 8) [36]. A convenient, direct regio- and stereoselective route to optically pure unusually fused or bridged tricyclic /3-lactams has been developed by the use of intramolecular nitrone-alkene cycloaddition reactions. For example, the aldehyde 21 can be transformed into nitrone 31 which subsequently was used for a variety... 

Horner-Wadsworth-Emmons and Wittig-Horner Olefination Reactions... 

The Wittig-Horner olefination can also be achieved in aqueous heterogeneous media (Rambaud et ai, 1984). Thus ( )-vinylphosphonates were prepared in good yields from aldehydes and tetraethylmethylene diphospho-nate in boiling water. Ethyl (diethylphosphono)acetates are alkylated in the same conditions providing in one pot a-acrylic acid esters (Kirschleger and Queignec, 1986) ... 

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