Pericyclic — anion-accelerated [3,3]-shift
Oxy-Cope rearrangement
How the Oxy-Cope rearrangement 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: KH (or NaH), 18-crown-6 optional; then H₃O⁺ work-up. Conditions: THF, 25 °C (neutral oxy-Cope: >200 °C). Bonds formed: C–C (C1–C6); enolate C=C → ketone C=O; bonds broken: C–C (C3–C4); O–H. Stereochemistry: Chair (or boat) TS; alkene geometry transferred. Rate and selectivity: 10¹⁰–10¹⁷-fold faster than neutral oxy-Cope (anion acceleration).
At a glance
Step 1: Alkoxide formation
A 1,5-hexadien-3-ol — a Cope substrate bearing a hydroxyl at C3 — is deprotonated by strong base (KH or NaH) to form the corresponding alkoxide, placing a full negative charge right next to the system about to rearrange.
Step 2: Anion-accelerated [3,3] shift
The same six-membered, three-arrow [3,3]-sigmatropic shift as the ordinary Cope rearrangement proceeds, but now dramatically accelerated — often by a factor of 10¹⁰–10¹⁷ — because the developing enolate in the product is far lower in energy than the alkoxide-destabilized starting material.
Step 3: Protonation and tautomerisation
The initial product is an enolate, which tautomerizes on workup to a ketone — this anion-accelerated rate enhancement is so large that oxy-Cope rearrangements routinely proceed at room temperature where an ordinary neutral Cope substrate would need forcing heat.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- NaH
- Sodium hydride. Insoluble, irreversible base: removes H⁺ and bubbles off H₂.
- KH
- Potassium hydride. Stronger/faster relative of NaH.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
How it compares with related reactions
| Oxy-Cope rearrangement | 2-Aza-Cope rearrangement | Eschenmoser-Claisen rearrangement | |
|---|---|---|---|
| Reagents | KH (or NaH), 18-crown-6 optional; then H₃O⁺ work-up | Homoallylic amine, aldehyde (to give the iminium), acid | Allylic alcohol, Me₂NC(OMe)₂CH₃ (DMA-DMA) |
| Conditions | THF, 25 °C (neutral oxy-Cope: >200 °C) | Mild heat or RT (cationic variant), CH₂Cl₂ or MeCN | Xylene or toluene, 110–160 °C (MeOH removed) |
| Stereochemistry | Chair (or boat) TS; alkene geometry transferred | Chair TS; stereo transferred | Chair TS; chirality transfer from the carbinol |
| Rate / selectivity | 10¹⁰–10¹⁷-fold faster than neutral oxy-Cope (anion acceleration) | Faster than all-carbon Cope (cationic N) | [3,3] step rate-limiting; no acid or base needed |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Oxy-Cope rearrangement?
KH (or NaH), 18-crown-6 optional; then H₃O⁺ work-up. Conditions: THF, 25 °C (neutral oxy-Cope: >200 °C).
Which bonds are formed and which are broken?
Formed: C–C (C1–C6); enolate C=C → ketone C=O. Broken: C–C (C3–C4); O–H.
What is the stereochemical outcome?
Chair (or boat) TS; alkene geometry transferred
What controls the rate or the selectivity?
10¹⁰–10¹⁷-fold faster than neutral oxy-Cope (anion acceleration)
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti