Transition-Metal-Free Selective Oxidation of Heterobenzylic C─H Bond in the Presence of Other Oxidizable C─H Bonds

Direct oxidation of sp³ C─H bond is an extremely important part of modern-day research in both academia and industry, because of the ubiquities of C─H bond in organic and biomolecules. However, challenges remain with regard to site-selectivity and environmental concerns, since mostly transition metals and hazardous oxidants are used. In this work, we disclose two different transition-metal-free oxidative approaches for the selective oxidation of heterobenzylic sp³ C─H bond in the presence of other oxidizable C─H bonds, like benzylic C─H and more reactive C(sp²)─H. We initially developed a visible light-assisted photocatalytic oxidation of the heterobenzylic C─H bond using Eosin Y (EY) as photocatalyst and K₂S₂O₈ as nontoxic terminal oxidant affording corresponding heteroaryl ketones. In another approach, the same reaction was performed in the absence of any photocatalyst or light, using TEMPO as the catalyst and K₂S₂O₈ as the oxidant. The reactions occur under ambient atmosphere, at very low temperatures, and exhibit high selectivity for the heterobenzylic C─H bond.