Palladium catalyzed
hydrodefluorination was developed for fine-tuning
the properties of fluoro-(hetero)aromatic compounds. The robust reaction
can be set up in air, requires only commercially available components,
and tolerates a variety of heterocycles and functionalities relevant
to drug discovery. Given the prevalence of fluorine incorporation
around metabolic hotspots, the corresponding deuterodefluorination
reaction may prove useful for converting fluorinated libraries to
deuterated analogues to suppress the oxidative metabolism by kinetic
isotope effects.