Rearrangement — alkene-assisted 1,2-shift
Semipinacol rearrangement
How the Semipinacol 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: Vinyl epoxide with an adjacent tertiary alcohol, Lewis acid (BF₃·OEt₂, TiCl₄ or SnCl₄). Conditions: CH₂Cl₂, –78 → 0 °C. Bonds formed: C=O; new C–C (migrated group); ring-expanded ketone; bonds broken: epoxide C–O; migrating C–C; O–H. Stereochemistry: Stereospecific, concerted anti 1,2-shift; creates a quaternary centre. Rate and selectivity: Ionisation to the allylic cation is rate-determining; ring strain relief speeds cyclobutanol expansion.
At a glance
Step 1: Lewis acid ionises the epoxide
An allylic or vinyl epoxide (or a related halohydrin) is activated by a Lewis acid at the leaving-group oxygen, generating a carbocation stabilized by the adjacent alkene — an allylic cation, rather than the simple alkyl cation of the classic pinacol rearrangement.
Step 2: Concerted 1,2-ring shift
A group on the carbon bearing the remaining hydroxyl migrates in a concerted 1,2-shift directly onto that allylic cation — the same core migration logic as the pinacol rearrangement, just triggered by an adjacent alkene-stabilized leaving group instead of a second, symmetric alcohol.
Step 3: Loss of H⁺ gives the ketone
Loss of a proton from the resulting oxocarbenium gives a ring-expanded or substituent-migrated carbonyl compound — 'semi' because only one of the two pinacol rearrangement's original hydroxyl groups is present, with an alkene standing in for the other.
Abbreviations and terms
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- Lewis acid
- Lewis acid. Electron-pair acceptor (AlCl₃, BF₃, TiCl₄…) that activates carbonyls and halides.
- BF3
- Boron trifluoride. Lewis acid (usually as the Et₂O complex).
- TiCl4
- Titanium tetrachloride. Strong, oxophilic Lewis acid that chelates carbonyls.
How it compares with related reactions
| Semipinacol rearrangement | Meisenheimer rearrangement | Pinacol rearrangement | |
|---|---|---|---|
| Reagents | Vinyl epoxide with an adjacent tertiary alcohol, Lewis acid (BF₃·OEt₂, TiCl₄ or SnCl₄) | Allylic tertiary amine N-oxide | Cat. H₂SO₄ or other strong acid |
| Conditions | CH₂Cl₂, –78 → 0 °C | Heat, 25–100 °C (neutral) | Heat, aqueous or neat acid |
| Stereochemistry | Stereospecific, concerted anti 1,2-shift; creates a quaternary centre | Suprafacial [2,3]; chirality transfer from N-oxide to carbon | Migratory aptitude: aryl, H > tertiary alkyl > methyl |
| Rate / selectivity | Ionisation to the allylic cation is rate-determining; ring strain relief speeds cyclobutanol expansion | Concerted, 5-membered envelope TS; unimolecular | Ionisation to the cation is rate-determining |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Semipinacol rearrangement?
Vinyl epoxide with an adjacent tertiary alcohol, Lewis acid (BF₃·OEt₂, TiCl₄ or SnCl₄). Conditions: CH₂Cl₂, –78 → 0 °C.
Which bonds are formed and which are broken?
Formed: C=O; new C–C (migrated group); ring-expanded ketone. Broken: epoxide C–O; migrating C–C; O–H.
What is the stereochemical outcome?
Stereospecific, concerted anti 1,2-shift; creates a quaternary centre
What controls the rate or the selectivity?
Ionisation to the allylic cation is rate-determining; ring strain relief speeds cyclobutanol expansion
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti