Theoretical Insights into Rare-Earth-Catalyst-Controlled Diastereo- and Enantioselective [3 + 2] Annulation of Aromatic Aldimines with Styrenes

Rare-earth-catalyzed annulation reactions using alkenes via C-H activation offer an atom-efficient approach to constructing cyclic compounds. However, the mechanisms underlying these reactions remain poorly understood, limiting the rational design of related catalytic systems. Recently, Hou and Cong reported an unprecedented example of rare-earth-catalyst-controlled diastereodivergent asymmetric [3 + 2] annulation of aromatic aldimines with alkenes. To elucidate the mechanisms and the origins of diastereo- and enantioselectivity, density functional theory calculations were performed. The results revealed that the styrene insertion step determines the stereoselectivity. Styrene insertion follows a similar metal-styrene interaction pattern across different catalysts. Specifically, during <i>cis</i>-insertion, styrene interacts strongly with the metal center, exhibiting significant Sc···Ph interactions, whereas such interactions are absent during <i>trans</i>-insertion. Thus, when the catalyst is employed with a small ligand, stereoselectivity is primarily governed by electronic factors, favoring the <i>cis</i>-insertion mode. In contrast, for the more sterically hindered catalyst, the Sc···Ph interactions in <i>cis</i>-insertion are insufficient to overcome the steric effects, leading to a preference for the <i>trans</i>-insertion mode, which minimizes steric hindrance. These findings offer deeper insights into the origins of catalyst-controlled diastereo- and enantioselectivity and will also contribute to the rational design of stereospecific annulation reactions in rare-earth catalysis.