Pericyclic — silyl ketene acetal [3,3]-shift
Ireland-Claisen rearrangement
How the Ireland-Claisen 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: LDA, then TMSCl; then H₃O⁺ workup. Conditions: THF, –78 °C → 25 °C or mild heat. Bonds formed: C–C (Cα–Cγ′); C=O (silyl ester); bonds broken: allylic C–O; α C–H. Stereochemistry: Enolate geometry transferred through a chair TS to the new stereocentres. Rate and selectivity: [3,3] shift is rate-limiting; faster than parent Claisen.
At a glance
Step 1: Enolate formation and silyl trapping
An allylic ester is deprotonated at its alpha carbon and trapped as a silyl ketene acetal — locking the enolate geometry (E or Z) in place as a stable, isolable species, giving far more control than a simple in-situ ester enolate would allow.
Step 2: [3,3]-sigmatropic shift through a chair-like ring
Heating this silyl ketene acetal triggers the same [3,3]-sigmatropic shift used by the parent Claisen rearrangement — three curved arrows moving through a closed, six-membered loop, breaking the allylic C–O bond as a new C–C bond forms.
Step 3: Hydrolysis gives the acid
Hydrolysis of the resulting silyl ester reveals a γ,δ-unsaturated carboxylic acid — because the enolate geometry was locked in before the sigmatropic step, this variant gives far more reliable control over the new stereocenter's configuration than the original Claisen rearrangement offers.
Abbreviations and terms
- TMS
- Trimethylsilyl. –Si(CH₃)₃; a small silicon group used to protect or activate.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- LDA
- Lithium diisopropylamide. Strong (pKa ≈ 36), bulky, non-nucleophilic base that makes kinetic enolates quantitatively.
- TMSCl
- Chlorotrimethylsilane. Silylating agent.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- Δ
- Heat. Reaction is run at elevated temperature.
How it compares with related reactions
| Ireland-Claisen rearrangement | Eschenmoser-Claisen rearrangement | 2-Aza-Cope rearrangement | |
|---|---|---|---|
| Reagents | LDA, then TMSCl; then H₃O⁺ workup | Allylic alcohol, Me₂NC(OMe)₂CH₃ (DMA-DMA) | Homoallylic amine, aldehyde (to give the iminium), acid |
| Conditions | THF, –78 °C → 25 °C or mild heat | Xylene or toluene, 110–160 °C (MeOH removed) | Mild heat or RT (cationic variant), CH₂Cl₂ or MeCN |
| Stereochemistry | Enolate geometry transferred through a chair TS to the new stereocentres | Chair TS; chirality transfer from the carbinol | Chair TS; stereo transferred |
| Rate / selectivity | [3,3] shift is rate-limiting; faster than parent Claisen | [3,3] step rate-limiting; no acid or base needed | Faster than all-carbon Cope (cationic N) |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Ireland-Claisen rearrangement?
LDA, then TMSCl; then H₃O⁺ workup. Conditions: THF, –78 °C → 25 °C or mild heat.
Which bonds are formed and which are broken?
Formed: C–C (Cα–Cγ′); C=O (silyl ester). Broken: allylic C–O; α C–H.
What is the stereochemical outcome?
Enolate geometry transferred through a chair TS to the new stereocentres
What controls the rate or the selectivity?
[3,3] shift is rate-limiting; faster than parent Claisen
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti