Investigating Reactivity and Selectivity in a Palladium-Catalyzed Heteroleptic Ligand System for Electrophilic Arene Fluorination

Methods to access fluorinated molecules are of significant interest to the medicinal and agrochemical industries. We report a series of high-valent PdIV complexes stabilized by two distinct ligand cores, which mediate electrophilic fluorination reactions with excellent yields and good regioselectivity. Using high-throughput experimentation and kinetic analysis, the distinct roles of each ligand were uncovered. Synthetic modulation of the catalyst alongside density functional theory transition state modeling provided evidence into the turnover-limiting step while revealing key insights into the origin of regioselectivity. This workflow presents a general strategy for exploring heteroleptic systems as well as synthetic enhancements to electrophilic fluorination reactions relevant to both industrial and academic settings.