Role of Ion-Pairs in Bronsted 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 H-1 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.