Pd-Catalyzed Nucleophilic Fluorination of Aryl Bromides

ABSTRACT: On the basis of mechanism-driven reaction design, a Pd-catalyzed nucleophilic fluorination of aryl bromides and iodides has been developed. The method exhibits a broad substrate scope, especially with respect to nitrogen-containing heteroaryl bromides, and proceeds with minimal formation of the corresponding reduction products. A facilitated ligand modification process was shown to be critical to the success of the reaction. In recent years, the synthesis of fluorinated arenes has attractedmuch attention from the community of synthetic organic chemists as a result of the importance of these compounds in pharmaceutical1 and radiological2 applications. Among the various strategies for their preparation,3 nucleophilic fluorination of aryl (pseudo)halides with a metal fluoride salt (MF) is ideal because of the wide availability of substrates and easy access to the fluoride source.4 In 2009, we reported a method for th