A Convenient Late‐Stage Fluorination of Pyridylic C−H Bonds with N‐Fluorobenzenesulfonimide. Issue 42 (6th October 2016)

• Record Type: Journal Article
• Authors: Meanwell, Michael; Nodwell, Matthew B.; Martin, Rainer E.; Britton, Robert
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 42(2016)
• Page Start: 13244
• Page End: 13248
• Publication Date: 2016-10-06
• Subjects: fluorination -- late-stage functionalization -- medicinal chemistry -- N-fluorobenzenesulfonimide -- pyridines; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201606323
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : 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.