Alkene synthesis — stabilized ylide
Horner-Wadsworth-Emmons (HWE) reaction
How the Horner-Wadsworth-Emmons (HWE) reaction works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Phosphonate ester (EtO)₂P(O)CH₂CO₂Et, NaH or NaOMe, aldehyde. Conditions: THF or DME, 0–25 °C. Bonds formed: C=C (E-alkene), P–O (phosphate); bonds broken: α C–H, C=O, C–P. Stereochemistry: Strong E-selectivity (trans). Rate and selectivity: Aldehyde addition rate-limiting; water-soluble phosphate easily removed.
At a glance
Step 1: Base forms the phosphonate carbanion
Base deprotonates a phosphonate ester alpha to a carbonyl, forming a resonance-stabilized carbanion — more stable, and more selective, than a classic Wittig ylide.
Step 2: Carbanion adds; oxaphosphetane forms
This carbanion attacks an aldehyde's carbonyl carbon, forming a betaine/oxaphosphetane intermediate just like the Wittig.
Step 3: Collapse: (E)-alkene + phosphate
Collapse of the ring ejects a soluble phosphate byproduct (easy to remove, unlike Wittig's phosphine oxide) and gives the alkene, strongly favoring the E isomer.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- NaOMe
- Sodium methoxide. Alkoxide base matched to methyl esters.
- NaH
- Sodium hydride. Insoluble, irreversible base: removes H⁺ and bubbles off H₂.
- TPPO
- Triphenylphosphine oxide. The thermodynamic sink of Wittig/Mitsunobu/Appel reactions.
How it compares with related reactions
| Horner-Wadsworth-Emmons (HWE) reaction | Wittig reaction | Julia-Kocienski olefination | |
|---|---|---|---|
| Reagents | Phosphonate ester (EtO)₂P(O)CH₂CO₂Et, NaH or NaOMe, aldehyde | Ph₃P=CH₂ (ylide, from Ph₃P⁺CH₃ Br⁻ + n-BuLi); acetaldehyde | 1-phenyl-1H-tetrazol-5-yl (PT) sulfone, KHMDS (or NaHMDS, LiHMDS), aldehyde |
| Conditions | THF or DME, 0–25 °C | THF, 0 °C → 25 °C; anhydrous, inert atmosphere | THF or DME, –78 °C → 25 °C |
| Stereochemistry | Strong E-selectivity (trans) | Unstabilised ylides: Z-alkene; stabilised: E-alkene | Highly E-selective (anti-adduct, then anti elimination) |
| Rate / selectivity | Aldehyde addition rate-limiting; water-soluble phosphate easily removed | Driven by the strong P=O bond of Ph₃P=O | One-pot; Smiles shift and elimination are fast after addition |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Horner-Wadsworth-Emmons (HWE) reaction?
Phosphonate ester (EtO)₂P(O)CH₂CO₂Et, NaH or NaOMe, aldehyde. Conditions: THF or DME, 0–25 °C.
Which bonds are formed and which are broken?
Formed: C=C (E-alkene), P–O (phosphate). Broken: α C–H, C=O, C–P.
What is the stereochemical outcome?
Strong E-selectivity (trans)
What controls the rate or the selectivity?
Aldehyde addition rate-limiting; water-soluble phosphate easily removed
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go