Mixed Metal Fluorides for the Fluorination of Ayltrifluoroborates in the Presence of Palladium Catalyst
Fluorinated hydrocarbons are vital compounds for both pharmaceuticals and biomedical research, appearing in such drugs as Lipitor, Seretide, and Crestor. There is also great deal of current interest about using the 18F isotope for radioimaging research. Unfortunately, its short half-life demands speedy, mild-condition, low toxicity, highly regioselective, in-house synthesis; and current techniques involve multiple steps, extreme conditions, toxic reagents, and long reaction times, while also being environmentally unfriendly. In 2012, Fier and Hartwig converted aryl iodides into aryl fluorides via a cationic copper reagent with silver fluoride, but reaction time is still too long for 18F. In 2013 and 2014, Al-Masum group showed how nitration of trifluoroborates can be accomplished via Palladium catalyzed, Suzuki cross-coupling in one-pot, minute reactions. Given the similarities in the stoichiometric behavior of nitro groups and fluorine atoms, and the efficacy of the double metallofluoride system, we hypothesize that it should be possible to achieve fluorination with correspondingly high regioselectivity under equivalently mild conditions and short reaction times by combining these methods. Using a two metallofluoride system consisting of Copper (II) Fluoride and a second metallofluoride, we applied Palladium-catalyzed, microwave-irradiated, cross-coupling chemistry to a variety of stable, pre-functionalized trifluoroborates. Products were filtered, evaporated and analyzed in chloroform-d via 1H, 13C, and 19F NMR, with product spectra compared to both starting materials and metallofluorides. Although desired products were not detected by NMR, work will continue on this project, as such an approach would dramatically reduce the reaction time, danger, and environmental impact of fluorination, making swift, simple, safe, green, in-house organofluorosynthesis viable.
Peter Giles Maximillian Welch,
"Mixed Metal Fluorides for the Fluorination of Ayltrifluoroborates in the Presence of Palladium Catalyst"
ETD Collection for Tennessee State University.