Computational insights into Rh-catalyzed ring-opening of cuneane: distinctive roles of alcohol nucleophiles

An unprecedented ring-opening transformation of cuneane to the pentalene framework, extending the “cubane scaffold editing” concept, was computationally investigated for the first time. We identify an initial rhodium-catalyzed valence isomerization mechanism, and a distinctive role of alcohols in the subsequent nucleophilic addition process, namely electrophile trapping and proton relay. Electronic structure and free energy analyses reveal the regio- and stereoselective formation of the thermodynamically stable final product despite competing reversible catalyst dissociation.