12.17:
Aldehydes and Ketones to Alkenes: Wittig Reaction Overview
The Wittig reaction converts aldehydes or ketones to alkenes using phosphorus ylide, or the Wittig reagent.
Phosphorus ylide is a neutral molecule with a negatively charged carbon and a positively charged phosphorus atom, stabilized by resonance. It is synthesized from unhindered alkyl halides in two steps.
First, triphenylphosphine attacks the alkyl halide via an SN2 process, forming a phosphonium salt.
The salt reacts with a strong base that deprotonates the weakly acidic α hydrogen, generating the carbanionic ylide nucleophile.
Wittig reactions are regioselective, as the new C⁠＝⁠C bond is formed explicitly at the carbonyl position.
The reactions are also stereoselective depending on the ylide.
Phosphorus ylides with electron-withdrawing groups—stabilized by additional resonance structure—predominantly generate E alkenes. Reagents with simple alkyl groups primarily form Z alkenes.
Steric crowding around the carbonyl group affects the yield of the products formed: Sterically hindered ketones give poor yields compared to unhindered aldehydes.
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 SN2 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.
