Carbon-fluorine bond formation is a challenging chemical transformation, especially when used for the synthesis of arylfluorides. Simple molecules can be fluorinated with fluorination methods developed during the last 100 years, molecules of greater complexity, however, cannot. The current inability of chemists to efficiently make complex organic fluorides by late-stage fluorination often prevents research in diverse areas, such as drug development and molecular PET imaging. The proposed research addresses the chemical challenges of carbon-fluorine bond formation to synthesize functionalized arylfluorides. Our strategy for carbon-fluorine bond formation is based on organometallic chemistry. We proposed Pd- and Ag- mediated fluorination reaction of arylstannanes, arylboronic acids, and arylsilanes. Additionally we propose to develop transition metal fluoride complexes that react as electrophilic fluorination reagents using anionic fluoride as ultimate fluorine source. We further propose to synthesize four biologically active molecules via late-stage fluorination using our transition-metal mediated approach. A long-term-goal of our research is the application of our fluorination reactions to the synthesis of currently unavailable PET tracers for molecular imaging using positron-emission tomography. The application of the fluorination reactions to molecular imaging is beyond the scope of this grant proposal.
Many of the most useful man-made molecules contain fluorine due to the unique, desired properties of fluorinated molecules. The current inability of chemists to make complex fluorinated molecules by late-stage fluorination often prevents research in diverse areas such as drug development and molecular PET imaging.
| Strebl, Martin G; Campbell, Arthur J; Zhao, Wen-Ning et al. (2017) HDAC6 Brain Mapping with [18F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination. ACS Cent Sci 3:1006-1014 |
| Goldberg, Nathaniel W; Shen, Xiao; Li, Jiakun et al. (2016) AlkylFluor: Deoxyfluorination of Alcohols. Org Lett 18:6102-6104 |
| Shi, Hang; Braun, Augustin; Wang, Lu et al. (2016) Synthesis of (18) F-Difluoromethylarenes from Aryl (Pseudo) Halides. Angew Chem Int Ed Engl 55:10786-90 |
| Boursalian, Gregory B; Ham, Won Seok; Mazzotti, Anthony R et al. (2016) Charge-transfer-directed radical substitution enables para-selective C-H functionalization. Nat Chem 8:810-5 |
| Neumann, Constanze N; Hooker, Jacob M; Ritter, Tobias (2016) Concerted nucleophilic aromatic substitution with (19)F(-) and (18)F(-). Nature 534:369-73 |
| Hoover, Andrew J; Lazari, Mark; Ren, Hong et al. (2016) A Transmetalation Reaction Enables the Synthesis of [(18)F]5-Fluorouracil from [(18)F]Fluoride for Human PET Imaging. Organometallics 35:1008-1014 |
| D'Amato, Erica M; Neumann, Constanze N; Ritter, Tobias (2015) Selective Aromatic C-H Hydroxylation Enabled by ? (6)-Coordination to Iridium(III). Organometallics 34:4626-4631 |
| Shen, Xiao; Neumann, Constanze N; Kleinlein, Claudia et al. (2015) Alkyl Aryl Ether Bond Formation with PhenoFluor. Angew Chem Int Ed Engl 54:5662-5 |
| Campbell, Michael G; Ritter, Tobias (2014) Late-Stage Fluorination: From Fundamentals to Application. Org Process Res Dev 18:474-480 |
| Campbell, Michael G; Ritter, Tobias (2014) Late-stage formation of carbon-fluorine bonds. Chem Rec 14:482-91 |
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