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

Abstract

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 BF4 – 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)-BF4 – system, thereby providing a potential avenue for enantioselective cuneane synthesis.