Electrochemical Fluorination of Organic Compounds Using a Hexafluorosilicate Salt as an Inexpensive and Widely Available Fluorine SourceClick to copy article linkArticle link copied!
- David M. KöpflerDavid M. KöpflerInstitute of Chemistry, NAWI Graz, University of Graz, Heinrichstrasse 28, 8010 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, AustriaMore by David M. Köpfler
- Gabriele LaudadioGabriele LaudadioInstitute of Chemistry, NAWI Graz, University of Graz, Heinrichstrasse 28, 8010 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, AustriaMore by Gabriele Laudadio
- Clara BovinoClara BovinoAdvanced Chemistry Technologies, Lonza AG, Visp CH-3930, SwitzerlandMore by Clara Bovino
- Michael BersierMichael BersierAdvanced Chemistry Technologies, Lonza AG, Visp CH-3930, SwitzerlandMore by Michael Bersier
- Ryan LittichRyan LittichAdvanced Chemistry Technologies, Lonza AG, Visp CH-3930, SwitzerlandMore by Ryan Littich
- Dominique M. RobergeDominique M. RobergeAdvanced Chemistry Technologies, Lonza AG, Visp CH-3930, SwitzerlandMore by Dominique M. Roberge
- Simon Wagschal*Simon Wagschal*Email: [email protected]Advanced Chemistry Technologies, Lonza AG, Visp CH-3930, SwitzerlandMore by Simon Wagschal
- C. Oliver KappeC. Oliver KappeInstitute of Chemistry, NAWI Graz, University of Graz, Heinrichstrasse 28, 8010 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, AustriaMore by C. Oliver Kappe
- David Cantillo*David Cantillo*Email: [email protected]Institute of Chemistry, NAWI Graz, University of Graz, Heinrichstrasse 28, 8010 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, AustriaSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, AustraliaMore by David Cantillo
Abstract
The introduction of fluorine into organic molecules is of the utmost importance in the preparation of active pharmaceutical ingredients (APIs). While a wide range of fluorine sources for organic synthesis have been used over the past decades, the associated safety risks, cost, or environmental impact are still serious limitations. Hexafluorosilicate salts are one of the most inexpensive and readily available sources of nucleophilic fluorine, but they have so far not been used in organic synthesis. Herein we report the first example of the use of a hexafluorosilicate salt as a reagent for the formation of C–F bonds. We have selected as the model reaction an electrochemical decarboxylative fluorination procedure. The synthesis of bis(5-ethyl-2-methylpyridin-1-ium) hexafluorosilicate(IV) was key to obtaining a soluble and reactive hexafluorosilicate salt. This protocol enabled the synthesis of a wide range of primary, secondary, and tertiary aliphatic fluorides (22 examples) in up to 85% yield. The electrochemical method was also successfully transferred to a flow electrolysis cell, demonstrating its robustness and scalability. Finally, we extended the scope of the fluorine source by demonstrating its applicability to electrochemical benzylic C–H fluorination.
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