title: Selective C-H fluorination of pyridines and diazines inspired by a classic amination reaction.
abstract: Fluorinated heterocycles are prevalent in pharmaceuticals, agrochemicals, and materials. However, reactions that incorporate fluorine into heteroarenes are limited in scope and can be hazardous. We present a broadly applicable and safe method for the site-selective fluorination of a single carbon-hydrogen bond in pyridines and diazines using commercially available silver(II) fluoride. The reactions occur at ambient temperature within 1 hour with exclusive selectivity for fluorination adjacent to nitrogen. The mild conditions allow access to fluorinated derivatives of medicinally important compounds, as well as a range of 2-substituted pyridines prepared by subsequent nucleophilic displacement of fluoride. Mechanistic studies demonstrate that the pathway of a classic pyridine amination can be adapted for selective fluorination of a broad range of nitrogen heterocycles.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Fier
authors.forename: John F
authors.initials: JF
authors.lastname: Hartwig
mesh_terms: D000586:Amination; D002244:Carbon / Q000737:chemistry; D005459:Fluorides / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D054879:Halogenation; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D009584:Nitrogen / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D018030:Silver Compounds / Q000737:chemistry
chemical_list: D011725:Pyridines; D018030:Silver Compounds; C105022:silver fluoride; D005461:Fluorine; D002244:Carbon; D006859:Hydrogen; D009584:Nitrogen; D005459:Fluorides