Olefinations Wittig-Horner

Tlie starting material for this Wittig-Horner-like olefination was easily accessible by reaction of benzo-l,3-dithiolium-tetrafluoroborate with trimethylphosphite in the presence of an equimolar amount of sodium iodide in dry acetonitrile under nitrogen at room temperature (93% yield). 

Recently, Meier et al. synthesized the most extended OP Vs (81) known to date [104]. Four different synthetic pathways were used for the generation of these OP Vs the final step involves the formation of one or two olefinic double bonds via a Wittig-Horner-type, a Siegrist-type or a McMurry-type condensation. 

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.

The cyclopropylphosphonate anion undergoes the stereoselective addition reaction with aldehydes [106]. Although the Wittig-Horner elimination is not observed at this stage, the olefinic compounds are produced by treatment of the adduct alcohols 201 with NaH in the presence of 18-crown-6 as illustrated in Scheme 76. 

Magnesium, 235 Samarium(II) iodide, 270 Titanium(IV) chloride, 304 Addition reactions to carbonyl groups—Addition of functionalized CARBON NUCLEOPHILES (see also Aldol reaction and other specific condensation reactions, Meth-ylenation, Peterson Olefination, Refor-matsky reaction, Wittig reaction, Wittig-Horner reaction)... 

Alternatively it is possible to have both steps, addition and elimination, occur spontaneously if appropriate reagents are employed. There are two common strategies in use the Wittig reaction and the Wittig-Horner reaction. The Wittig olefination uses a phosphorus-stabilized carbanion (ylid) as a nucleophile and a carbonyl compound as an electrophile. Typically the ylid is generated in situ from a triphenylphosphonium salt and a strong base such as LDA or an alkyl lithium. 

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. 

Another popular olefination-reduction sequence starts with commercially available ketone 122, transformed into olefin 123 using a Wittig or Wittig-Horner reaction [103] (illustrated in Scheme 11.32). Reduction of the double bond proceeds with high stereocontrol to yield the alio derivative 124. The cis arrangement at C2-C3 allowed formation of lactone 125 and the synthesis of avenaciolide 126 [104,105]. 

The Wittig, Horner-Wadsworth-Emmons, Peterson, and Julia Olefination Reactions... 

---