Nature research paper: [18F]Difluorocarbene for Positron Emission Tomography
F-difluoromethylated molecules in high molar activity is largely an unsolved problem, despite the indispensability of the difluoromethyl group for pharmaceutical drug discovery. We report herein a general solution by introducing carbene chemistry to the field of nuclear imaging with a [F-difluoromethylation processes. In contrast to the tens of known difluorocarbene reagents, thisF-reagent is carefully designed for facile accessibility, high molar activity and versatility.
The issue of Ais solved using an assay examining the likelihood of isotopic dilution upon variation of the electronics of the difluorocarbene precursor. Versatility is demonstrated with multiple [F]difluorocarbene based reactions including O–H, S–H and N–H insertions, and cross-couplings that harness the reactivity of ubiquitous functional groups such as phenols,-heteroarenes, and aryl boronic acids that are easy to install.
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