Role of Ion-Pairs in Brønsted Acid Catalysis

Phosphoric acids have emerged as efficient organo-catalysts for various reactions. Despite widespread use, details of the reaction intermediates giving rise to stereocontrol have remained elusive. To clarify the nature of the catalyst-substrate interaction, we characterize and quantify catalyst-substrate complex formation by combining dielectric spectroscopy, quantum chemistry, and ¹H NMR spectroscopy. For a series of different solvents, the interaction between substrate and catalyst is dominated by ion-pairing, rather than hydrogen bonding, at ambient conditions. Correlation of ion association with catalytic enantioselectivity provides evidence that close-contact ion-pairing is essential for stereocontrol and that dissociation into free ions dramatically reduces enantioselectivity.