Dakin oxidation

The Dakin oxidation starts with (1) nucleophilic addition of a hydroperoxide ion to the carbonyl carbon, forming a (2) tetrahedral intermediate.

[1][2][3] The Dakin oxidation has two rate-limiting steps: nucleophilic addition of hydroperoxide to the carbonyl carbon and [1,2]-aryl migration.

M-hydroxy compounds do not concentrate electron density at the migrating carbon (12a, 12b, 12c, 12d); their aryl groups' migratory aptitude remains low.

The benzylic hydrogen, which has the highest migratory aptitude, migrates instead (8), forming a phenyl carboxylic acid (9).

Consequently, oxidation accelerates as pH increases toward the pKa of hydrogen peroxide and hydroperoxide concentration climbs.

Deprotonation of the second peroxidic oxygen would prevent [1,2]-aryl migration because the lone oxide anion is too basic to be eliminated (2).

Following an intramolecular proton transfer (16,17), the tetrahedral intermediate collapses, [1,2]-aryl migration occurs, and water is eliminated (18).

Finally, deprotonation of the carbonyl oxygen yields the collected products and regenerates the acid catalyst (23).

[6] Using an ionic liquid solvent with catalytic methyltrioxorhenium (MTO) dramatically accelerates Dakin oxidation.

[7] In addition, the Dakin oxidation is useful in the synthesis of indolequinones, naturally occurring compounds that exhibit high anti-biotic, anti-fungal, and anti-tumor activities.