C–H Functionalization of Pyridines via Oxazino Pyridine Intermediates: Switching to para-Selectivity under Acidic Conditions

para -Selective C–H functionalization of pyridines holds a significant value but remains underdeveloped. Site-switchable C–H functionalization of pyridines under easily tunable conditions expedites drug development. We recently reported a redox-neutral dearomatization–rearomatization strategy for meta -C–H functionalization of pyridines via oxazino pyridine intermediates. Here, we demonstrate that these oxazino pyridine intermediates undergo highly para -selective functionalization simply by switching to acidic conditions. A broad scope of para -alkylated and arylated pyridines is prepared through radical as well as ionic pathways. These mild and catalyst-free methods are applied to the late-stage para -functionalization of drugs using pyridines as the limiting reagents. Consecutive meta,para -difunctionalization of pyridines is also achieved with complete regiocontrol relying on the pH-dependent reactivity of oxazino pyridines.