Wittig reagents

In organic chemistry, Wittig reagents are organophosphorus compounds of the formula R3P=CHR', where R is usually phenyl. They are used to convert ketones and aldehydes to alkenes: Because they typically hydrolyze and oxidize readily, Wittig reagents are prepared using air-free techniques. They are typically generated and used in situ. THF is a typical solvent. Some are sufficiently stable to be sold commercially. Wittig reagents are usually prepared from a phosphonium salt, which is in turn prepared by the quaternization of triphenylphosphine with an alkyl halide. Wittig reagents are usually derived from a primary alkyl halide. Quaternization of triphenylphosphine with secondary halides is typically inefficient. For this reason, Wittig reagents are rarely used to prepare tetrasubstituted alkenes. The alkylphosphonium salt is deprotonated with a strong base such as n-butyllithium: [Ph3P+CH2R]X− + C4H9Li → Ph3P=CHR + LiX + C4H10 Besides n-butyllithium (nBuLi), other strong bases like sodium and potassium t-butoxide (tBuONa, tBuOK), lithium, sodium and potassium hexamethyldisilazide (LiHMDS, NaHMDS, KHDMS, where HDMS = N(SiMe3)2), or sodium hydride (NaH) are also commonly used. For stabilized Wittig reagents bearing conjugated electron-withdrawing groups, even relatively weak bases like aqueous sodium hydroxide or potassium carbonate can be employed. The identification of a suitable base is often an important step when optimizing a Wittig reaction. Because phosphonium ylides are seldom isolated, the byproduct(s) generated upon deprotonation essentially plays the role of an additive in a Wittig reaction. As a result, the choice of base has a strong influence on the efficiency and, when applicable, the stereochemical outcome of the Wittig reaction. Electron-withdrawing groups (EWGs) enhance the ease of deprotonation of phosphonium salts. This behavior is illustrated by the finding that deprotonation of triphenylcarbethoxymethylphosphonium requires only sodium hydroxide. The resulting triphenylcarbethoxymethylenephosphorane is somewhat air-stable.