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.
Meanwell, Michael,Nodwell, Matthew B.,Martin, Rainer E.,Britton, Robert
C(α)-substituted 4-methylpyridines have been N-lithiated and reacted with chlorotrimethylsilane and other electrophiles. The lithiated C(α)-NMe2 substituted intermediate shows an interesting dichotomy of behavior towards electrophiles: It represents the borderline between compounds for which an extreme N or C(α) regionucleophilicity is observed.
Anders,Opitz,Bauer
p. 1221 - 1227
(2007/10/02)
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