Wittig Reaction Overview and Mechanism

Overview

• Wittig reaction converts ketones and aldehydes into alkenes using phosphonium ylides.
• Product structure and stereochemistry follow directly from the carbonyl and ylide substituents.

Wittig Reaction Basics

• The oxygen of the carbonyl is replaced by the carbon group attached to the ylide carbon.
• To predict the product, conceptually align the ylide carbon with the carbonyl carbon and “swap” the C=O for a C=C.
• The Wittig reaction is especially useful for building specific carbon–carbon double bonds.
• Products can be mixtures of E (trans) and Z (cis) isomers when each alkene carbon has two different substituents.

Product Prediction & Isomerism

• Draw the C=C and attach:
  • Carbonyl substituents on one side.
  • Ylide substituents (including hydrogen) on the other.
• If both alkene carbons bear two different groups, E/Z isomers are possible.
• Example: a ketone with ethyl and methyl plus a ylide carbon bearing H and methyl gives E/Z alkene mixture.
• For cyclohexanone, one alkene carbon is part of the ring (top and bottom equivalent), so no E/Z isomerism; only one alkene forms.

Representation of Ylides

• Ylides can be shown as:
  • Phosphorus with a positive charge and adjacent negatively charged carbon, or
  • A P=C double bond (neutral overall).
• These are resonance forms and are used interchangeably.

Mechanism of the Wittig Reaction

• Triphenylphosphine (Ph₃P) reacts with a methyl or primary alkyl halide via SN2 to give a phosphonium salt.
• A strong base (e.g., butyllithium) deprotonates the carbon next to phosphorus, forming a resonance-stabilized ylide.
• The nucleophilic ylide carbon attacks the electrophilic carbonyl carbon while oxygen bonds to phosphorus, giving a four-membered oxaphosphetane.
• Oxaphosphetane collapses: C–P and C–O bonds break, giving the alkene and triphenylphosphine oxide.
• Both cis (Z) and trans (E) alkenes form; the E isomer is usually more stable due to reduced steric repulsion.

Key Terms

• Wittig reaction: Carbonyl → alkene using a phosphonium ylide.
• Phosphonium ylide: Species with P⁺ and adjacent C⁻ (or P=C) used to install the alkene fragment.
• SN2: Single-step nucleophilic substitution favored by methyl and primary halides.
• Oxaphosphetane: Four-membered P–C–C–O intermediate.
• E/Z isomerism: Configuration of alkene substituents (E = opposite, Z = same side).