title: A Convenient Late-Stage Fluorination of Pyridylic C-H Bonds with N-Fluorobenzenesulfonimide.
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.
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Meanwell
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Nodwell
authors.affiliation: Medicinal Chemistry, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070, Basel, Switzerland.
authors.forename: Rainer E
authors.initials: RE
authors.lastname: Martin
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada. rbritton@sfu.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Britton
keywords: N-fluorobenzenesulfonimide; fluorination; late-stage functionalization; medicinal chemistry; pyridines