Alkyl Fluoride Synthesis via Cu-Mediated Deacetylative Fluorination
Zining Zhang1, Kezhi Chen1, Peng Liu2
1Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United States.
Journal of the American Chemical Society
|June 3, 2025
Summary
This study introduces a novel copper-catalyzed method to transform methyl ketones into valuable alkyl fluorides. This deacylative fluorination expands synthetic options for creating diverse organofluorine compounds.
Area of Science:
- Organic Chemistry
- Organometallic Chemistry
- Fluorination Chemistry
Background:
- Growing demand for diverse alkyl fluorides in various applications.
- Need for new synthetic methodologies to access alkyl fluorides from common precursors.
- Ketones as potential, yet underexplored, starting materials for fluorination.
Purpose of the Study:
- To develop a novel deacylative fluorination method for methyl ketones.
- To expand the synthetic toolbox for organofluorine compound synthesis.
- To explore copper-mediated C-F bond formation pathways.
Main Methods:
- Copper-mediated deacylative fluorination of methyl ketones.
- Utilized a ketone activation reagent and a nucleophilic fluoride source.
- Employed computational studies to elucidate reaction mechanisms.
Main Results:
- Successfully converted a wide range of methyl ketones to corresponding alkyl fluorides.
- Demonstrated broad functional group tolerance and late-stage fluorination capability.
- Achieved synthesis of α,α-dideuterated fluorides and controlled synthesis of mono-, di-, and trifluoroalkanes.
Conclusions:
- The developed Cu-mediated deacylative fluorination is a versatile method for alkyl fluoride synthesis.
- The reaction offers significant advantages for late-stage functionalization and complex molecule synthesis.
- Computational studies suggest Cu(III)-mediated C-F bond formation via fluorine atom transfer or SN2 pathways.
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