(Radio)haloaromatic moieties are prevalent in drug molecules and radiopharmaceuticals, driving significant and sustained interest in the development of methods for synthesizing these compounds. There is a particular demand for rapid, efficient, and reproducible (radio)halogenation of electron-deficient or sterically hindered aromatic rings when the halide is in significant stoichiometric deficiency. We report a convenient method of regioselective bismuth-mediated radiohalogenation of arylboronates that tolerates a wide range of functional groups and is effective with electron-rich, electron-deficient, electron-neutral, and sterically crowded aryl and heteroaryl rings. As a proof of concept, we prepared 77Br-, 124I-, and 211At-labeled derivatives of radiopharmaceuticals, including the prostate-specific membrane antigen (PSMA) inhibitor MIP-1095, with excellent radiochemical conversion (80-99%), radiochemical yield (42-78%), and radiochemical purity (>99%) at molar activities exceeding 250 GBq/μmol. These experiments highlight the suitability of this method for the synthesis of (radio)haloaromatic drugs and radiopharmaceuticals for clinical applications.
Debnath et al. (Fri,) studied this question.
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