Synthesis routes Wittig-Horner

Macrocyclic ketones. This reagent has been used for cycloolefination of acetylenic dialdehydes (Wittig-Horner reaction) as a route to muscone, exaltone, and civetone. A synthesis of the last ketone (3) is formulated (equation 1). 

Vitamin A acetate is an important nutrient additive and its synthesis is now carried out on a technical scale. The three major routes of preparation used today were developed by HofFmann-La Roche, Rhone Poulenc, and BASF [43]. For the work presented here, we were particularly concerned with the Wittig-Horner reaction between a C15 and a C5 precursor as it occurs in the BASF process [44,45]. This study describes the investigation of important process parameters for a synthesis that involves a thermally unstable ylide intermediate. In the current experiments, this intermediate is generated in situ and immediately converted in order to simulate the conditions in the technical process. However, while in a conventional process the reaction hardly can be performed under isothermal conditions due to the exothermic heat of reaction of about 250kJ/mol, the microreactor setup offers the opportunity to study relevant process parameters such as temperature, concentrations of starting materials, and mixing protocol of the components. 

Enamines are highly valued intermediates in organic synthesis. Almost invariably they are prepared by reaction of a carbonyl compound with a secondary amine. In principle, another attractive route to enamines could be based on construction of the double bond by a Wittig- or Horner-Wittig reaction. The enamines J thus obtained could be easily converted into the corresponding homologous aldehydes, if desired fitted with an extra electrophilic substituent at the original carbonyl carbon atom. 

On the synthetic side, single diastereomers of P-keto phosphine oxides have been generated from intermolecular acylation of phosphine oxides using either chiral esters or chiral phosphine oxides. In most cases, reduction of the ketone products was not affected by the presence of extra chiral centres. Addition of metallated phosphine oxides to proline-derived ketoaminals provides a new route to optically active P-hydroxy phosphine oxides. The P-hydroxy phosphine oxide 97 has been prepared by the caesium fluoride mediated reaction of silyl-substituted phosphine oxide 98 and benzaldehyde." The synthesis of two (E)-(6-hydroxy-2-hexen-l-yl)diphenylphosphine oxides (99) has been reported. The Horner-Wittig reactions of these compounds with various carbonyl compounds... 

The isomeric isoxazole-substituted phosphine oxides (61) and (63) have been synthesised and used in Horner-Wittig reactions to prepare isoxazoles of types (62) and (64) regiospecifically.32 An alternative approach to (62) and (64) involves reaction of the isoxazole aldehydes (e.g. 65) with alkyldiphenylphosphine oxide anions (Scheme 11). The routes described have been applied to the synthesis of isoxazoles containing leukotriene-like carbon chains. 

Fluprostenol was marketed in form of its racemate by ICI as a contraceptive in the veterinary sector. The synthetic route developed for this product proceeds via the Corey lactone, whereby the side-chains are built up using Horner-Wadsworth-Emmons or Wittig reactions. Travoprost, the enantio-merically pure isopropyl ester of fluprostenol, is a potent anti-glaucoma drug, for which Chirotech Technology Ltd. has published an interesting synthesis (Fig. 5.102). [229]... 

Scheme 4.5 shows the most important direct routes for preparing soluble PAVs Heck coupling, and Wittig and Horner polycondensations. The two biggest advantages of these routes are that they avoid the formation of tolane and other defects seen in the precursor routes, and also that they allow the synthesis... 

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