Unveiling the Critical Roles of Amine Additives and Water for Half-Sandwich Sc Catalysts in Annulation Reactions

In order to uncover the critical roles of amine additives and water for Sc catalysts, this study theoretically investigates the <i>trans</i>-diastereoselective [3 + 2] annulation of α,β-unsaturated aldimines with alkenes catalyzed by a C₅Me₄SiMe₃-ligated half-sandwich scandium catalyst. 1-adamantylamine (AdNH₂) is found to facilitate the cyclization step by lowering the Gibbs free energy by 3.6 kcal mol^–1 and promote catalyst regeneration via 1-adamantylamine-mediated hydrogen exchange.

The newly identified 1-adamantylamine-promoted borrowing-hydrogen ring-opening/ring-closing steps enable configuration inversion of intermediate <b>5</b><i><b>t</b></i> to its isomer <b>5</b><i><b>c</b></i>, thereby establishing a <i>cis</i>-selective pathway with an energy span of 29.4 kcal mol^–1. The important water-assisted [3 + 2] annulation pathway is unveiled with an energy span of 31 kcal mol^–1, and the inert Sc–O bonds of Sc–OH intermediates could impose a kinetic penalty that attenuates overall catalytic efficiency.