Molecular Recognition in Asymmetric Counteranion Catalysis: Understanding Chiral Phosphate-Mediated Desymmetrization

We describe the first
theoretical study of a landmark example of
chiral anion phase-transfer catalysis: the enantioselective ring-opening
of meso-aziridinium and episulfonium cations promoted
by asymmetric counteranion-directed catalysis (ACDC). The mechanism
of ion-pairing, ring-opening, and catalyst deactivation have been
studied in the condensed phase with both classical and quantum methods
using explicitly and implicitly solvated models. We find that the
stability of chiral ion-pairs, a prerequisite for asymmetric catalysis,
is dominated by electrostatic interactions at long range and by CH···O
interactions at short range. The decisive role of solvent upon ion-pair
formation and of nonbonding interactions upon enantioselectivity are
quantified by complementary computational approaches. The major enantiomer
is favored by a smaller distortion of the substrate, demonstrated
by a distortion/interaction analysis. Our computational results rationalize
the stereoselectivity for several experimental results and demonstrate
a combined classical/quantum approach to perform realistic modeling
of chiral counterion catalysis in solution.