CycloSiFA: The Next Generation of Silicon‐Based Fluoride Acceptors for Positron Emission Tomography (PET)

The ring‐opening Si‐fluorination of a variety of azasilole derivatives cyclo‐1‐(iPr2Si)−4‐X−C6H3−2‐CH2NR (4: R=2,6‐iPr2C6H3, X=H; 4 a: R=2,4,6‐Me3C6H2, X=H; 9: R=2,6‐iPr2C6H3, X=tBuMe2SiO; 10: R=2,6‐iPr2C6H3, X=OH; 13: R=2,6‐iPr2C6H3, X=HCCCH2O; 22: R=2,6‐iPr2C6H3, X=tBuMe2SiCH2O) with different 19F‐fluoride sources was studied, optimized and the experience gained was used in a translational approach to create a straightforward 18F‐labelling protocol for the azasilole derivatives [18F]6 and [18F]14. The latter constitutes a potential clickable CycloSiFA prosthetic group which might be used in PET tracer development using Cu‐catalysed triazole formation. Based on our findings, CycloSiFA has the potential to become a new entry into non‐canonical labelling methodologies for radioactive PET tracer development. Cyclic azasilole derivatives undergo ring‐opening with 18F– anions under mild conditions and with high radiochemical yield. They represent a novel class of Silicon Fluoride Acceptor systems (CycloSiFA) and hold great potential for convenient kit‐like labelling procedures in different medicinal applications.