Unraveling Nonradiative Effects and Reaction Mechanism of Aza-Paternò-Büchi Reaction Catalyzed by a Cu(I) Complex

The azetidine heterocyclic framework, a four-membered nitrogen-containing ring system, is prevalent in natural product derivatives and pharmacologically compounds. As one of the powerful tools for generating azetidine, photocycloaddition catalyzed by Cu complex has achieved great success. However, the mechanism at the atomic level remains elusive. Herein, combining the density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, the reaction mechanism and the physical origin of diastereomeric selectivity are explored comprehensively. Our calculations reveal that tris(pyrazolyl)borate Cu (TpCu) initially coordinates with norbornene (Norb) to generate TpCu(Norb) complex. Upon photoexcitation, TpCu(Norb) can eventually populate the triplet state, in which the C=C double bond is activated. The initial C-C bonding reaction occurs in the triplet state, followed by an intersystem crossing process to the ground state, where the C-N bond forms. Depending on the spatial orientation of the approaching imine, either from one-atom bridge (-CH₂- group) or two-atom bridge (-CH₂-CH₂- group), products with <i>exo</i>- and <i>endo</i>- diastereomers can be generated. Notably, a structural rearrangement is required to form the <i>endo</i>- products. Both <i>syn</i>- and <i>anti</i>-diastereomers are observed as products in the transformation due to the relative orientations of imine and Norb. The present work not only unlocks the detailed reaction mechanism but also provides valuable insights into the construction of azetidine.