Insights on the Origin of Regiodivergence in the Parallel Kinetic Resolution of rac-Aziridines Using a Chiral Lanthanum–Yttrium Bimetallic Catalyst

Parallel kinetic resolution of racemic mixtures is an important method used in asymmetric synthesis of chiral compounds. In a recent example, a rac-cis-2,3-substituted chiral N-benzoyl aziridine was reacted with dimethyl malonate, in the presence of a La–Y heterobimetallic chiral BINAM Schiff base (L) catalyst, to form enantiomerically pure (ee > 98%) γ-amino acid derivatives through a ring-opening reaction in near-quantitative yields from both the enantiomers (∼48%). High regio- and enantioselectivities even with a rac-aziridine, having C2 and C3 substituents as similar as ethyl and n-propyl. Through a comprehensive computational investigation, we delineate the origin of regio-divergent and enantioselective formation of γ-amino ester derivatives. The Gibbs free energy of the transition state for the ring-opening at the propyl substituted C2 carbon leading to 3-benzamidoheptan-4-yl malonate is found to be 7.2 kcal/mol lower than that at the ethyl substituted C3 carbon in the case of (2R,3S)-aziridine. A r...