Oxidative Fragmentations and Skeletal Rearrangements of Oxindole Derivatives

An oxidative sequence for the conversion of oxindoles to structurally distinct heterocyclic scaffolds and aniline derivatives is disclosed by the combination of a copper-catalyzed C–H peroxidation and subsequent base-mediated fragmentation reaction. In contrast to classic enzymatic (i.e., kynurenine pathway) and biomimetic methods (i.e., Witkop–Winterfeldt oxidation) for oxidative indole cleavage, this protocol allows for the incorporation of external nucleophiles. The new transformation displays broad functional group tolerance and is applicable to tryptophan derivatives, opening potential new avenues for postsynthetic modification of polypeptides, bioconjugation, and unnatural amino acid synthesis.