Chiral Phosphoric Acid-Catalyzed Enantioselective Direct Arylation of Iminoquinones: A Case Study of the Model Selectivity.

Chiral phosphoric acid (CPA)-catalyzed enantioselective arylation reactions have attracted immense attention recently. However, the preferential activation model in the stereodetermining step is controversial, and hence, the origin of enantioselectivity is still far from being understood. Two stereochemical models are provided on the basis of the asymmetric arylations of iminoquinones with naphthylamines (reaction 1) or naphthols (reaction 2) catalyzed by (R/S)-TRIP to explain the high enantioselectivity and the effect of CPAs scaffolds. Unexpectedly, our calculations reveal that substrate naphthylamines or naphthols prefer enantioselective aminal formation model II or 1,4-addition model I, respectively, which is the reverse of Tan's and Xu's model. The different noncovalent and steric interactions between catalysts and substrates are responsible for the observed model preference. Moreover, the enantioselectivity arises from distortion (reaction 1) and noncovalent interactions (reaction 2) that discriminate between the diastereomeric transition states. We further investigated the effect of SPINOL-based CPAs on the enantioselectivity and found that the more rigid skeleton and a smaller binding pocket lead to lower enantioselectivity as compared with that of BINOL-based CPA. The new insights into the reaction activation model rationalize the stereoselectivity outcome of direct asymmetric arylation reactions, and our general model can be extended to related transformations.