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.本文系统开展了针对五元杂芳基溴化物的钯（Pd）催化氟化反应这一挑战性课题的深入研究。晶体学研究与密度泛函理论（DFT）计算结果表明，该转化反应的核心挑战性步骤为从钯(II)配合物上发生的五元杂芳基氟化物的C-F还原消除过程。基于上述研究结果，本团队发现多种邻位带有苯基的杂芳基溴化物可在催化条件下实现高效氟化。高活性的2-溴代唑类化合物（如8-溴咖啡因）同样可作为该反应的可行底物。