Study of Ground State Interactions of Enantiopure Chiral Quaternary Ammonium Salts and Amides, Nitroalkanes, Nitroalkenes, Esters, Heterocycles, Ketones and Fluoroamides

Chiral phase‐transfer catalysis provides high level of enantiocontrol, however no experimental data showed the interaction of catalysts and substrates. 1H NMR titration was carried out on Cinchona and Maruoka ammonium bromides vs. nitro, carbonyl, heterocycles, and N−F containing compounds. It was found that neutral organic species and quaternary ammonium salts interacted via an ensemble of catalyst +N−C−H and (sp2)C−H, specific for each substrate studied. The correspondent BArF salts interacted with carbonyls via a diverse set of +N−C−H and (sp2)C−H compared to bromides. This data suggests that BArF ammonium salts may display a different enantioselectivity profile. Although not providing quantitative data for the affinity constants, the data reported proofs that chiral ammonium salts coordinate with substrates, prior to transition state, through specific C−H positions in their structures, providing a new rational to rationalize the origin of enantioselectivity in their catalyses.
1H NMR titration experiments were carried out on Cinchona and Maruoka type quaternary ammonium salts, by using neutral ligands. The data clarified the principal interactions involved between catalyst and reactants, showed the binding of halides and non‐coordinating anion BArF to chiral ammonium species, and provided a guide to understanding the enantioselective processes mediated by this class of organocatalysts.