Formal -C-H-Fluorination of Pyridines and Isoquinolines through Dearomatized Oxazinopyridine Intermediates.

Organofluorine compounds, including fluorinated pyridines and isoquinolines, play a crucial role in pharmaceuticals, agrochemicals, and materials science. However, step-economic selective C-H-functionalization to access these fluorinated azaarenes is still underexplored, with selective -C-H-fluorination proving to be especially elusive. Here we present a practical method for formal -C-H-fluorination of pyridines and isoquinolines. By applying an oxazinoazaarene-based temporary pyridine dearomatization strategy with Selectfluor as an electrophilic F-source, fluorination of pyridines was achieved with exclusive C3-selectivity in moderate to good yields. The same strategy can also be applied to the formal -C-H-fluorination of isoquinolines. Late-stage-functionalization of drugs, drug precursors, and ligands as well as a large-scale one-pot dearomatization-fluorination-rearomatization reaction further demonstrate the synthetic utility of this approach.