Reactions of Aldehydes and Ketones: Baeyer–Villiger Oxidation

Baeyer–Villiger oxidation converts aldehydes to carboxylic acids and ketones to esters by inserting an oxygen atom next to the carbonyl carbon. The reaction uses peracids such as m-chloroperoxybenzoic acid (mCPBA) or peracetic acid, often with an acid catalyst. For cyclic ketones, the reaction produces lactones instead of simple esters.

The carbonyl oxygen is first protonated, making the carbonyl carbon more electrophilic. The terminal oxygen of the peracid then attacks the carbonyl carbon nucleophilically. After loss of a proton, this produces a tetrahedral intermediate called the Criegee intermediate, which proceeds to rearrangement.

Baeyer–Villiger oxidation is regioselective because different groups have different migratory aptitudes. The order follows: –H > –CR3 > –CHR2 ≈ –Ph > –CRH2 > –CH3. With two possible migration pathways, the group with higher migratory aptitude preferentially migrates, making one product predominate over the other.

During the concerted intramolecular rearrangement, three events occur simultaneously: the carbonyl bond reforms, a group migrates from carbon to oxygen, and the weak peroxide O–O bond cleaves. This releases the final product—either a carboxylic acid or ester—while retaining stereochemistry at the migrating center for asymmetrical substrates.

For aromatic substrates, electron-donating groups accelerate the migration process by stabilizing the developing positive charge during rearrangement. Conversely, electron-withdrawing groups retard migration by destabilizing this charge. This electronic effect influences which group migrates and determines the reaction rate and selectivity.

The acid catalyst protonates the carbonyl oxygen, increasing the electrophilicity of the carbonyl carbon and facilitating nucleophilic attack by the peracid. The catalyst also protonates the carboxylate intermediate, promoting the concerted rearrangement that follows and ultimately releasing the final product efficiently.

Common peracids include m-chloroperoxybenzoic acid (mCPBA), perbenzoic acid, peracetic acid, hydrogen peroxide, and tert-butyl hydroperoxide. These reagents provide the oxygen atom that inserts next to the carbonyl carbon, with mCPBA and peracetic acid being particularly popular in laboratory and industrial synthesis applications.