Computational Research on Ag(I)-Catalyzed Cubane Rearrangement: Mechanism, Metal and Counteranion Effect, Ligand Engineering, and Post-Transition-State Desymmetrization.

Ag(I) salts have demonstrated superior catalytic activity in the cubane-cuneane rearrangement. This research presents a comprehensive mechanistic investigation using high-level computations. The reaction proceeds via oxidative addition (OA) of Ag(I) to the C-C bond, followed by C-Ag bond cleavage and subsequent dynamically concerted carbocation rearrangement. The OA of Ag(I) exhibits significant more electrophilic nature than classical transition metal-induced OA, and the superior catalytic activity of Ag(I) is attributed to the accessibility of a highly electrophilic "bare" Ag center and a relatively weak Ag-C bond. However, the highly Lewis acidic nature of the Ag(I) center limits the substrate scope. To address this problem, ligand and counteranion screening was conducted, revealing that chiral biarylether ligands in combination with BF as the counteranion offer both enhanced reactivity and improved chemoselectivity while suppressing the Lewis acidity. Additionally, quasi-classical molecular dynamics simulations indicate the possibility of a novel desymmetrization pathway through post-transition-state dynamics in the biarylether-Ag(I)-BF system, thereby providing a potential avenue for enantioselective cuneane synthesis.