A Multistep, One-Pot Bismuth-Mediated Radiohalogenation Method for Preparation of Radiopharmaceuticals for Imaging and Targeted Therapy

(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.