Despite significant progress in the development of site-selective aliphatic C-H oxidations over the past decade, the ability to oxidize strong methylene C-H bonds in the presence of more oxidatively labile aromatic functionalities remains a major unsolved problem. Such chemoselective reactivity is highly desirable for enabling late-stage oxidative derivatizations of pharmaceuticals and medicinally important natural products that often contain such functionality. Here, we report a simple manganese small-molecule catalyst Mn(CF3-PDP) system that achieves such chemoselectivity via an unexpected synergy of catalyst design and acid additive. Preparative remote methylene oxidation is obtained in 50 aromatic compounds housing medicinally relevant halogen, oxygen, heterocyclic and biaryl moieties. Late-stage methylene oxidation is demonstrated on four drug scaffolds, including the ethinylestradiol scaffold where other non-directed C-H oxidants that tolerate aromatic groups effect oxidation at only activated tertiary benzylic sites. Rapid generation of a known metabolite (piragliatin) from an advanced intermediate is demonstrated Ver menos