The development of sulfonated terpyridine ligands for control of regioselectivity in palladium-catalysed fluorination of anilides

Fluorinated arenes are ubiquitous in synthetically and medicinally valuable compounds. Direct fluorination of arene C-H bonds is an attractive disconnection to these targets, but methods are far more restricted than analogous bromination or chlorination and those that do exist often yield inseparable mixtures of regioisomers. We describe the superimposition of a non-covalent directing strategy to a recently reported method for palladium-catalysed arene fluorination which utilised terpyridine ligands on the key reactive complex. We have synthesised and evaluated a range of terpyridine ligands that bear a pendant sulfonate group at various different positions with the aim of engaging in hydrogen bonding with an anilide substrate to impact the otherwise non-selective <i>ortho</i>/<i>para</i> ratio that is typically obtained with standard terpyridine ligands. This has enabled the identification of a ligand that can enable <i>para</i>-selectivity in the fluorination of a range of trifluoroacetanilides. We envisage this will be of use in selective arene fluorination but also demonstrates the potential of targeted non-covalent strategies for control of regioselectivity in transition metal catalysis.