First-Principles Characterization of Noncovalent Interactions in the Enantioselective Oxetane Ring Opening via SPHENOL-Based Chiral Phosphoric Acid Catalyst.

The asymmetric ring-opening reaction of 3,3-substituted oxetanes catalyzed by chiral phosphoric acid (CPA) derived from a newly developed SPHENOL (2,2',3,3'-tetrahydro-1,1'-spirobi[phenalene]-9,9'-diol) framework was investigated by performing density functional calculations. The plausible transition states were traced by considering the oxetane activation mode. The energy profiles obtained for various substrates provide a rational understanding of the reaction at the atomic level. The truncation models help to attribute the reaction initiation and origin of enantioselectivity to three types of noncovalent interactions between the catalyst and the substrate. The Quantum theory of atoms in molecules (QTAIM), Noncovalent Interactions (NCI) Plots, and Wiberg Bond Index (WBI) provide conclusive evidence of the origin of stereoselectivity for the intramolecular desymmetrization of the five substrates considered here. The current study establishes that the SPHENOL-derived CPA catalyst forges enantioselective desymmetrization of 3,3-substituted oxetanes with higher enantiomeric excess in comparison to previously known SPINOL- and BINOL-derived CPA catalysts.