A Chiral Phosphoric Acid Structure Leads to Strong Interactions That Affected Selectivity of the N-Hydroxyalkylation Reactions: A Density Functional Theory Study

Chiral phosphoric acids (CPAs) can regulate reaction selectivity via catalyst–substrate noncovalent interactions (NCIs). Most studies remain macroscopic and have not addressed how CPA structures modulate the interaction strength and thereby selectivity. This study reveals that, in CPA-catalyzed N-hydroxyalkylation reactions, the CPA backbone rigidity and substituent structure promote stronger interactions, thereby enhancing enantioselectivity. An ordered π system facilitates the formation of more pronounced π–π stacking.