mCPBA

meta-Chloroperoxybenzoic Acid

Most Common Uses

• oxidation of alkenes to epoxides (the Prilezhaev reaction)
• oxidation of aldehydes and ketones to esters (Baeyer-Villiger oxidation)

Oxidation of Alkenes to Epoxides

Stereospecificity

Epoxidations are highly stereospecific—meaning that the stereochemistry of the product is specified by the stereochemistry of the reactant.

Thus, when trans-2-butene (shown above) is treated with mCPBA, the methyl groups will be trans in the product.

While, when cis-2-butene (shown below) is treated with mCPBA, the methyl groups will be cis in the product.

Regioselectivity

Epoxidations are regioselective. When multiple alkenes are present, the more electron-rich alkene will preferentially react.

In the example above, the endocyclic (inside the ring) alkene will react faster because it is more substituted, and therefore more electron rich, than the exocyclic (outside the ring) alkene.

Oxidation of Aldehydes and Ketones

In the Baeyer-Villiger oxidation, ketones are converted into esters when treated with mCPBA.

Symmetric ketones will give the same product regardless of which side gets the oxygen. In the example above, a cyclic ester (lactone) is formed.

Asymmetric ketones react regioselectively due to different groups having different rates of migration (called the migratory aptitude) in the reaction. The migratory aptitudes are:

H > 3° > 2° ≈ Ph > 1° > methyl

Thus, when acetophenone is treated with mCPBA, the oxygen will be preferentially inserted between the carbonyl group and the phenyl group because phenyl groups have a higher migratory aptitude than a primary alkyl group.

Aldehydes will give the corresponding carboxylic acid upon treatment with mCPBA because hydrogen has the greatest migratory aptitude overall.

In the example above, the oxygen is preferentially inserted between the carbonyl group and the hydrogen because hydrogen migrates more rapidly (has a higher migratory aptitude) than a primary alkyl group.

Additional Uses

• oxidation of silyl enol ethers to silyl α-hydroxy ketones (the Rubottom oxidation)

The silyl α-hydroxy ketone product can be converted into the corresponding α-hydroxy ketone using standard deprotection of the TMS ether.