In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides

A thorough
investigation of the challenging Pd-catalyzed fluorination
of five-membered heteroaryl bromides is presented. Crystallographic
studies and density functional theory (DFT) calculations suggest that
the challenging step of this transformation is C–F reductive
elimination of five-membered heteroaryl fluorides from Pd­(II) complexes.
On the basis of these studies, we have found that various heteroaryl
bromides bearing phenyl groups in the ortho position can be effectively
fluorinated under catalytic conditions. Highly activated 2-bromoazoles,
such as 8-bromocaffeine, are also viable substrates for this reaction.