Palladium Catalyzed Hydrodefluorination of Fluoro-(hetero)arenes
Joseph J Gair1, Ronald L Grey1, Simon Giroux1
1Vertex Pharmaceuticals Inc , 50 Northern Avenue , Boston , Massachusetts 02210 , United States.
Abstract:
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.
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