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

Rare-earth metal catalysts have unique catalytic properties. In order to uncover the critical roles of amine additives and water for Sc catalysts, this study theoretically investigates the trans-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 5 t to its isomer 5 c, thereby establishing a cis-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. The substituent effects of the unique C5Me4SiMe3 ligand on the Sc catalyst are systematically elucidated by modulating the catalyst structures. The computed results suggested that electron-withdrawing substituents inhibit the rate-determining styrene insertion step, while the van der Waals interactions between the Cp ligand and the NMC (N-tert-butyl α-methyl cinnamaldimine) ligand framework facilitate this step.