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Updated: May 22, 2025

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
Published on: June 10, 2021
3-Selective Pyridine Fluorination via Zincke Imine Intermediates
Marie A Hart1, Benjamin J H Uhlenbruck1, Jeffrey N Levy1
1Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
Abstract:
Fluorine substitution is a widely used approach to improve the properties of drugs bearing aromatic rings and has spawned numerous new methods for C-F bond formation. Reactions employing C-H bond precursors are particularly valuable, but pyridine-applicable variants are rare, especially at the C3-position. We developed an approach using ring-opened Zincke imines that undergo regioselective C-F bond formation with electrophilic fluorination reagents, resulting in C3-fluoropyridines after ring closure. This process can accommodate a wide range of pyridine substitution patterns, tolerates various appended functional groups, and is viable for the late-stage fluorination of pyridine-containing drugs.
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