ArticleChemical science2026
Ligand-enabled palladium-catalyzed late-stage C-H fluorination of arenes.
Article in Chemical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Fluorinated molecules play a vital role in medicinal chemistry, offering improved metabolic stability and bioavailability. Herein, we report a ligand-enabled C-H fluorination protocol enabled by palladium catalysis and a newly designed bidentate ligand. This strategy allows for regioselective fluorination of arenes and heteroarenes using Selectfluor as an electrophilic fluorine source under mild reaction conditions. The fluorination reaction proceeds efficiently, showcasing broad substrate scope and functional group tolerance. Notably, the methodology enables late-stage fluorination of a wide range of complex pharmaceuticals and biologically relevant molecules. Mechanistic investigations support a Pd(ii)/Pd(iv) catalytic pathway. Notably, we accomplished the one-step synthesis of fluorouracil under mild conditions, a significant advancement over traditional harsh multi-step protocols.
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