12.17 : Aldehydes and Ketones to Alkenes: Wittig Reaction Overview

The Wittig reaction is the conversion of carbonyl compounds-aldehydes and ketones-to alkenes using phosphorus ylides, or the Wittig reagent. The reaction was pioneered by Prof. Georg Wittig, for which he was awarded the Nobel Prize in Chemistry.

Phosphorus ylide is a neutral molecule containing a negatively charged carbon directly bonded to a positively charged phosphorus atom. The molecule is stabilized by resonance.

The Wittig reagents are synthesized from unhindered alkyl halides in two steps. At first, the alkyl halide undergoes an S_N2 attack by a triphenylphosphine molecule generating a phosphonium salt. Next, in the presence of a strong base such as butyllithium, sodium hydride, or sodium amide, the salt undergoes deprotonation of the weakly acidic α hydrogen, producing the carbanionic ylide nucleophile.

Wittig reactions are regioselective, as the new C＝C bond is formed explicitly at the carbonyl position. The stereoselectivity depends on the nature of the phosphorus ylide. Ylides with electron-withdrawing groups, such as carbonyl or aromatic rings that are stabilized by additional resonance structure, predominantly generate E alkenes. Alternatively, Wittig reagents with simple alkyl groups primarily form Z alkenes.

The yield of Wittig reactions is influenced by steric crowding around the carbonyl group. Ketones that are sterically more hindered give poor yields compared to aldehydes. A variation of the Wittig reaction is the Horner–Wadsworth–Emmons reaction that involves a phosphonate ester reagent producing the E alkene as the major product.