Theoretical investigation of enantioselectivity of cage-like supramolecular assembly: the insights into the shape complementarity and host-guest interaction.

Enantioselectivity in the aza-Cope rearrangement of a guest molecule encapsulated in a cage-like supramolecular assembly Ga4 L6 [L = 1,5-bis(2',3'-dihydroxybenzamido)naphthalene] is investigated using density functional theory and ab initio molecular orbital calculations. Reaction pathways leading to R- and S-enantiomers encapsulated in the Ga4 L6 are explored. The reaction barriers and the stabilities of the prochiral structures differed in the Ga4 L6 , resulting that the product with an R structure is favorably produced in the Δ-structure Ga4 L6 . The large energy difference in the prochiral structures in the Ga4 L6 was attributed to the deformation of the bulky substituent. The host-guest interaction energy raises the reaction barrier for the product with an S structure. The previous study suggested that the different stability of the prochiral substrates in the assembly was the origin of the enantioselectivity, and the suggestion is supported by our computational finding. In addition, our results show that the difference in the reaction barriers also importantly contributes to the enantioselectivity.