A Convenient Late-Stage Fluorination of Pyridylic C−H Bonds with N-Fluorobenzenesulfonimide

• Published in: Angewandte Chemie International Edition Vol. 55; no. 42; pp. 13244 - 13248
• Main Authors: Meanwell, Michael, Nodwell, Matthew B., Martin, Rainer E., Britton, Robert
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 10.10.2016; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Basicity; Chemistry; Chemistry, Multidisciplinary; Fluorination; late-stage functionalization; Lipophilicity; medicinal chemistry; Metabolism; N-fluorobenzenesulfonimide; Physical Sciences; Pyridines; Science & Technology; Selectivity; Stability; C(SP)-H BONDS; ANNULATED PYRIDINES; ELECTROPHILIC FLUORINATION; fluorination; OMEPRAZOLE; REACTIVITY; FLUORIDE; N-fluorobenzenesulfonimide; BENZYLIC FLUORINATION; pyridines; PHOTOCATALYTIC FLUORINATION; HETEROCYCLES; late-stage functionalization; INHIBITORS; medicinal chemistry
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201606323

Pyridine features prominently in pharmaceuticals and drug leads, and methods to selectively manipulate pyridine basicity or metabolic stability are highly sought after. A robust, metal‐free direct fluorination of unactivated pyridylic C−H bonds was developed. This convenient reaction shows high functional‐group tolerance and offers complimentary selectivity to existing C−H fluorination strategies. Importantly, this late‐stage pyridylic C−H fluorination provides opportunities to rationally modulate the basicity, lipophilicity, and metabolic stability of alkylpyridine drugs. Fashionably late: A robust, metal‐free direct fluorination of unactivated pyridylic C−H bonds was developed. This convenient reaction shows high functional‐group tolerance and offers complementary selectivity to existing C−H fluorination strategies. Importantly, this late‐stage pyridylic C−H fluorination provides opportunities to rationally modulate the basicity, lipophilicity, and metabolic stability of alkylpyridine drugs.