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

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.