Understanding how charge-charge interaction affects the stereochemistry of enamine fluorination by chiral primary amine catalysis

Electrostatic interaction, especially electrostatic attraction, usually plays critical roles in controlling the reactivity and selectivity in catalytic transformations; however, the like-charge repulsion, which is ubiquitous in physical systems, is rarely applied in reaction control. Herein we disclosed an unexpected like-charge repulsion induced enantio-control mode in primary aminecatalyzed fluorination reactions with 1-fluoro-2,4,6-trimethylpyridinium triflate. The ionic reaction works favorably in both highly polar (methanol) and non-polar (hexane) solvents, a seldom observed phenomenon in asymmetric catalysis. Erying plot analysis showed that an inversion temperature existed in MeOH, which was explained by the solvent-solute cluster model under different temperatures. Density functional theory (DFT) study and energy decomposition analysis (EDA) verified that the like-charge repulsion takes effect in polar solvent methanol, while in nonpolar solvents, the steric repulsion associated with ion-pair was found to be the major effect for the observed enantioselectivity.