Selectfluor-Mediated Chlorination and Fluorination of Arenes: Late-Stage Functionalization of APIs and Its Biological Effects

By using active pharmaceutical ingredients (APIs) previously recovered from expired drugs, it is shown that Selectfluor can act as a reagent for operationally simple late-stage fluorination and chlorination of electron-rich arenes under mild reaction conditions. As shown in mechanistic experiments, aromatic fluorination thereby competes with chlorine-for-fluorine exchange on Selectfluor and subsequent aromatic chlorination, whereat the chloride ions may either be provided by the hydrochloride salt of the respective API or by triethylammonium chloride. Biological testing of the fluorinated or chlorinated APIs at adrenergic, dopaminergic, muscarinergic, opioid or serotoninergic receptors demonstrated that improved binding affinities can be achieved via this straightforward strategy.

Automated summary

By using active pharmaceutical ingredients (APIs) recovered from expired drugs, Selectfluor can act as a reagent for simple fluorination and chlorination reactions on electron-rich arenes under mild conditions. Mechanistic experiments show that aromatic fluorination competes with chlorine-for-fluorine exchange on Selectfluor, resulting in aromatic chlorination. The resulting fluorinated or chlorinated APIs exhibit improved binding affinities at various receptors.