Oxidation — oxygen insertion
Baeyer-Villiger oxidation of a ketone
How the Baeyer-Villiger oxidation of a ketone 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: mCPBA or CH₃CO₃H (peracid). Conditions: CH₂Cl₂, 25 °C; cat. acid helps. Bonds formed: C–O (ester), C=O; bonds broken: O–O, C–C (migrating). Stereochemistry: Retention at the migrating carbon. Rate and selectivity: Migratory aptitude: tert > cyclohexyl ≈ sec > Ph > prim > Me.
At a glance
Step 1: Peracid adds to the carbonyl
A peracid's electrophilic oxygen is attacked by the ketone's carbonyl oxygen lone pair, forming a tetrahedral Criegee intermediate with a peroxide-like O–O bond.
Step 2: Criegee intermediate: migration with O–O cleavage
The group better able to stabilize positive charge migrates from carbon to the adjacent oxygen as the O–O bond breaks — the same 1,2-migration logic as Beckmann, just onto oxygen instead of nitrogen.
Step 3: Ester (lactone) and carboxylic acid
The result is an ester: a new oxygen has been inserted directly into the bond next to the original carbonyl carbon.
Abbreviations and terms
- Me
- Methyl. –CH₃.
- Ph
- Phenyl. –C₆H₅.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- mCPBA
- meta-Chloroperoxybenzoic acid. Peracid that transfers an electrophilic oxygen (epoxidation, Baeyer–Villiger).
How it compares with related reactions
| Baeyer-Villiger oxidation of a ketone | Swern oxidation of a primary alcohol | Dakin oxidation | |
|---|---|---|---|
| Reagents | mCPBA or CH₃CO₃H (peracid) | DMSO, (COCl)₂, then Et₃N | H₂O₂, NaOH (aq.) |
| Conditions | CH₂Cl₂, 25 °C; cat. acid helps | CH₂Cl₂, –78 °C then warm to 25 °C | Aqueous base, 0–25 °C |
| Stereochemistry | Retention at the migrating carbon | Retains α-stereocentres (no epimerization) | None (aromatic); aryl migrates with retention of its ring |
| Rate / selectivity | Migratory aptitude: tert > cyclohexyl ≈ sec > Ph > prim > Me | Activation at –78 °C; ylide collapse fast on warming | Migration of the electron-rich aryl is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Baeyer-Villiger oxidation of a ketone?
mCPBA or CH₃CO₃H (peracid). Conditions: CH₂Cl₂, 25 °C; cat. acid helps.
Which bonds are formed and which are broken?
Formed: C–O (ester), C=O. Broken: O–O, C–C (migrating).
What is the stereochemical outcome?
Retention at the migrating carbon
What controls the rate or the selectivity?
Migratory aptitude: tert > cyclohexyl ≈ sec > Ph > prim > Me
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go