Investigating Reactivity and Selectivity in a Palladium-Catalyzed Heteroleptic Ligand System for Electrophilic Arene Fluorination
Shubham Deolka, Mohammad H. Samha, Aleria Garcia Roca, Graham C. Haug, James R. Howard, David Dalmau, Jesus Sandres, Serhii Vasylevskyi, Ryan T. VanderLinden, Robert S. Paton, Matthew S. Sigman
Abstract
Methods to access fluorinated molecules are of significant interest to the medicinal and agrochemical industries. We report a series of high-valent Pd IV 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.