Competing Noncovalent Interactions Control the Stereoselectivity of Chiral Phosphoric Acid Catalyzed Ring Openings of 3-Substituted Oxetanes

The noncovalent interactions responsible for enantioselectivity in organocatalytic oxetane ring openings were quantified using density functional theory (DFT) computations. Data show that the mode of stereoinduction in these systems differs markedly for different substituted oxetanes, highlighting the challenge of developing general stereochemical models for such reactions. For oxetanes monosubstituted at the 3-position, the enantioselectivity is primarily due to differential CH···π interactions between the mercaptobenzothiazole nucleophile and the aromatic backbone of the catalyst. This can be contrasted with 3,3-disubstituted oxetanes, for which interactions between an oxetane substituent and the phosphoric acid functionality and/or the anthryl groups of the catalyst become more important. The former effects are particularly important in the case of 3-OH-substituted oxetanes. Overall, these reactions demonstrate the diversity of competing noncovalent interactions that control the stereoselectivity of many phosphoric acid catalyzed reactions.