Roles of Nonadiabatic Processes, Reaction Mechanism, and Selectivity in Cu-Catalyzed [2 + 2] Photocycloaddition of Norbornene and Acetone to Oxetane

Abstract

Oxetane has been extensively studied for its applications in medicinal chemistry and as a reactive intermediate in synthesis. Experiments report a Cu-catalyzed [2 + 2] photocycloaddition of acetone and norbornene to oxetane, which is proposed to deviate from the conventional Paterno-Buchi reaction. However, its mechanism at the atomic level is not clear. In this study, we used a combination of multistate complete active space second-order perturbation theory (MS-CASPT2) and density functional theory to systematically investigate the reaction mechanism and elucidate the factors contributing to the diastereomeric selectivity. Initially, the formation of the TpCu-(Norb) complex is achieved by strong interaction between tris(pyrazolyl)borate Cu(I) (TpCu) and norbornene in the ground state (S 0 ). Upon photoexcitation, TpCu(Norb) eventually decays to the T 1 state, in which TpCu(Norb) attacks acetone to initiate subsequent reactions and produces final endo-or exo-oxetane products. All these reactions initially involve the C−C bond formation in the T 1 state thereto leading to a ring-opening intermediate. This intermediate then undergoes a nonradiative transition to the S 0 state, producing a five-membered ring intermediate, from which the C−O bond is formed, leading to the experimentally dominant exo-product. In contrast, the endo-oxetane formation requires a rearrangement process after the C−C bond is formed because of the large steric effects. As a consequence, the different reaction pathways generating exo-and endo-products exhibit large differences in the free-energy barriers, which results in a diastereomeric selectivity observed experimentally. Additionally, the nonradiative transition is found to play an important role in facilitating these reaction steps. The present computational study provides valuable mechanistic insights into Cu-catalyzed photocycloaddition reactions.