Synthetic C6-Functionalized Aminoflavin Catalysts Enable Aerobic Bromination of Oxidation-Prone Substrates.

Flavoenzymes catalyze oxidations via hydroperoxide intermediates that result from activation of molecular O2 . These reactions-such as hydroxylation and halogenation-depend on the additional catalytic activity of functional groups in the peptide environment of the flavin cofactor. We report synthetic flavin catalysts that contain C6 amino modifications at the isoalloxazine core and are consequently capable of mediating halogenations outside the peptide surrounding. The catalysts are competent in the selective, biomimetic bromination of oxidation-prone phenols, flavones, and flavanones using a halide salt in combination with 2,6-lutidinium oxalate as a flavin reductant under visible-light irradiation. Our studies show the beneficial effect of stacked bisflavins as well as the catalytic activity of the flavin modifications. The designed flavin catalysts outperform isolated natural (-)-riboflavin and contribute to the continuing search for tailored flavins in oxidation reactions.