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Please login to access the full content or check if you have access via Variation 1: Wittig Alkenation with Lithium Salt Free Ylides

DOI: 10.1055/sos-SD-027-00847

Schobert, R.; Gordon, G. J.Science of Synthesis, (2004271019.

The Z-selective Wittig alkenation of an aldehyde is normally carried out by adding it to a chilled solution of an unstabilized ylide in an aprotic solvent, such as hexane, benzene, toluene, tetrahydrofuran, dioxane, dimethylformamide, or hexamethylphosphoric triamide. The solution is then quickly warmed to room temperature and stirred until the completion of the reaction (this is normally indicated by the disappearance of the typical orange-red color). Gentle heating may be required in some cases. The ylide solution is customarily prepared in situ at room temperature or above by treating a slurry of the phosphonium salt in one of the solvents listed above with a non-lithium base such as sodium hydride, sodium amide,[‌137‌] or preferably sodium hexamethyldisilazanide,[‌311‌] which is soluble even in warm hexane. Removal of the residual phosphonium and the inorganic sodium salts is possible by filtration under a protective gas atmosphere, but is not normally necessary. Ammonia and hexamethyldisilazane are volatile byproducts and can be removed by evaporation of the (filtered) ylide solution under reduced pressure and redissolution of the residue in an appropriate absolute solvent. Separation of the product alkene and phosphine oxide is usually achieved by crystallizing (freezing out) most of the latter from hexane at 20°C, and removing the rest by column chromatography on silica gel (hexane/diethyl ether 3:1 or neat dichloromethane as eluents). The two-step procedure is illustrated in Scheme 33, which refers to the syntheses of some representative alkenes 93.[‌17‌,‌311‌,‌473‌‌477‌] Ylides bearing polar amino or carboxylic acid groups bonded to P-aryl residues have also been developed; these give easily removable water-soluble phosphine oxides.[‌477‌] The E/Z ratio of alkene isomers produced is best established by gas chromatography or high-pressure liquid chromatography. E-Selective alkenation of aldehydes is usually achieved by reactions with preformed isolated stabilized ylides in a wide range of solvents, including protic ones and water, at elevated temperatures.[‌187‌] Reaction rates and E-selectivities may be increased by catalytic additives such as benzoic acid or lithium salts.[‌478‌]

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