Wittig Reaction
The Wittig olefination reaction involves the formation of C–C double bonds, olefins, from carbonyl compounds and phosphorous ylides.
General features:
1. The phosphorous ylides can be prepared from a triaryl- or trialkylphosphine (e.g., triphenylphosphine) and an alkyl halide followed by deprotonation with a suitable base (RLi, NaH, NaOR…). 2. Stabilized ylides have at least one strong electron-withdrawing group (-CO2R), which stabilizes the formal negative charge on the carbon. Ylides that have one aryl or alkenyl substituents are less stabilized. Ylides with only alkyl substituents are the least stable. 3. Many factors determine the stereoselectivity of the reaction. In general terms, stabilized ylides tend to deliver (E)-alkenes, while nonstabilized ylides are prone to give the (Z)-olefins. 4. The ylides are sensitive to moisture and oxygen. 5. Phosphorous ylides are chemoselective, reacting faster with aldehydes than ketones, and remaining intact in the presence of ester or amides. 6. Common solvents in this reaction are diethyl ether, toluene, THF, DME, and MTBE.
Wittig Reaction
Reaction Mechanism
1. Preparation of the phosphonium salt. 2. Formation of the phosphorous ylide by the base. 3. Nucleophilic addition leads to the formation of the betaine. 4. Formation of an oxaphosphetane intermediate. 5. Elimination of triphenylphosphine oxide yields the z-alkene.
Experimental Procedure
To a suspension of methyltriphenyl phosphonium bromide (8.0 eq) in anhydrous toluene (500 mL) was added nBuLi (2.5 M in hexane, 7.5 eq) at room temperature in a dropwise manner, and the resultant mixture was then stirred at the same temperature for 1 h.
To a solution of the ketone (12.40 mmol, 1.0 eq) in THF (150 mL) was added the solution prepared above at 0 ºC via a syringe in a dropwise manner, and the reaction mixture was stirred at 0 ºC for 30 min. the reaction was quenched by addition of a saturated solution of NH4Cl, and the mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over sodium sulfate. The solvent was removed under vacuum, and the residue was purified by a flash chromatography on silica gel to give the corresponding olefin (92% yield).
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