Baeyer–Villiger oxidation — Carbonyl & Enolate Breadth

Almost every reaction of a ketone in this course happens at the carbonyl carbon or at the α carbon. The Baeyer–Villiger oxidation does something else: it inserts an oxygen atom into a carbon–carbon bond, turning a ketone into an ester.

R–CO–R′ + mCPBA → R–CO–O–R′

The reagent is a peroxyacid, most often mCPBA — the same one that makes epoxides from alkenes. A peroxyacid carries an O–O bond with a good leaving group on the far side, which is the structural feature both reactions exploit.

The mechanism, and where the interesting step is

The peroxyacid's terminal oxygen adds to the carbonyl carbon, giving a tetrahedral intermediate — the Criegee intermediate.
That intermediate collapses by migration: one of the two groups on the original carbonyl carbon moves, with its bonding pair, onto the adjacent oxygen. The O–O bond breaks at the same time and a carboxylate leaves.

The migration is the step worth understanding. A group leaves one carbon and arrives at an oxygen without ever being free, taking its electrons with it — a 1,2-shift, the same motion that rearranges a carbocation, running here on a neutral intermediate.

The migrating group keeps its configuration. Because the bond never breaks fully, a stereocenter that migrates arrives with its arrangement intact. That is the fact worth remembering, because it makes the reaction usable on a chiral substrate where almost nothing else is.

Which group migrates

A ketone has two groups and only one moves, so a question about a Baeyer–Villiger is nearly always a question about which. The order is:

tertiary > cyclohexyl ≈ secondary ≈ benzyl ≈ aryl > primary > methyl

The reason is that the migrating carbon carries partial positive character in the transition state, so the group best able to support a positive charge migrates. For the alkyl groups that is the carbocation stability order arriving from a different direction. Aryl is the case where the shortcut strains: a phenyl cation is badly unstable, yet aryl migrates well, because the transition state is bridged rather than a free cation and the ring stabilizes it at the ipso carbon.

The practical consequence is a rule you can use without recalling the whole series: with a methyl ketone, the methyl essentially never migrates, so the other group does and the product is the acetate ester of that group. Methyl is the worst migrator in the list, which makes methyl ketones the most predictable substrates.

Rings become lactones

Acetophenone gives phenyl acetate, not methyl benzoate. Reading the names tells you which group moved: in phenyl acetate the oxygen sits between the phenyl and the carbonyl, so the phenyl is what migrated onto it and the methyl stayed where it was.The order is not a separate fact to memorize. Partway through the shift the migrating carbon is electron-poor, so whatever stabilizes a carbocation stabilizes this transition state — same ranking, arriving from a different direction. The practical shortcut: in a methyl ketone the methyl essentially never migrates, so the product is the acetate ester of whatever the other group was.

Run it on a cyclic ketone and the migration is intramolecular, so the ring does not open — it expands by one atom, and that atom is oxygen. A cyclohexanone gives a seven-membered lactone, a cyclopentanone gives a six-membered one.

This is one of the few reliable ring-expansion reactions at this level, and the only one that puts a heteroatom into the ring while doing it.

Selectivity against an alkene

mCPBA epoxidizes alkenes, so a substrate with both a ketone and an alkene has a competition. The alkene usually wins, because epoxidation is faster — which means a Baeyer–Villiger on such a substrate needs the alkene protected or the sequence reordered.

Note how much this section reuses. The reagent is the epoxidation reagent, the migration is the carbocation 1,2-shift, the migratory aptitude order is the carbocation stability order, and the product is an ester you already know how to hydrolyze. Nothing here is new machinery; it is familiar machinery pointed at a bond nobody else touches.

What carries forward

A peroxyacid inserts an oxygen between the carbonyl carbon and the group best able to carry positive charge. Methyl ketones give acetate esters of the other group, cyclic ketones give lactones one atom larger, and the migrating group keeps its stereochemistry. Retrosynthetically, an ester whose two halves look like an awkward esterification is worth checking against the ketone it would come from.