Silapiperidine-silicon-fluoride acceptors (Pip-SiFA) for ¹⁸F-radiolabelling

Silicon fluoride acceptors (SiFAs) are promising radiopharmaceutical motifs that promote mild and rapid ¹⁸F-labeling via isotope exchange (SiFEx). Nevertheless, their use in biologically active small molecules is complicated by their poor pharmacokinetic properties that stem from their high lipophilicity and large steric profiles. In an effort to overcome these limitations, we report here the synthesis and properties of fluorosilapiperidines (Pip-SiFAs), which retain SiFEx efficiency on an endocyclic Si center that approaches more pharmacologically compatible motifs.