Control of site-selectivity in chemical reactions that occur remote from existing functionality remains a major challenge in synthetic chemistry. We describe a strategy that enables three of the most commonly used crosscoupling processes to occur with high site-selectivity on dichloroarenes which bear acidic functional groups. We have achieved this by repurposing an established sulfonylated phosphine ligand to exploit its inherent bifunctionality. Mechanistic studies suggest that the sulfonate group engages in attractive electrostatic interactions with the associated cation of deprotonated substrate, guiding cross-coupling to the chloride at the arene meta-position. This counterintuitive combination of anionic ligand and anionic substrate demonstrates an alternative design principle when considering applying non-covalent interactions to direct catalysis.

Axial chirality features prominently in molecules of biological interest as well as chiral catalyst designs, and atropisomeric 2,2′-biphenols are particularly prevalent. Atroposelective metal-catalyzed cross-coupling is an attractive and modular approach to access enantioenriched biphenols, and yet existing protocols cannot achieve this directly. We address this challenge through the use of enantiopure, sulfonated SPhos ( sSPhos ), an existing ligand that has until now been used only in racemic form and that derives its chirality from an atropisomeric axis that is introduced through sulfonation. We believe that attractive noncovalent interactions involving the ligand sulfonate group are responsible for the high levels of asymmetric induction that we obtain in the 2,2′-biphenol products of Suzuki–Miyaura coupling, and we have developed a highly practical resolution of sSPhos via diastereomeric salt recrystallization.