Mechanistic Insights from Density Functional Theory into Rh/Acid-Catalyzed Synthesis of 1,2-Dihydroquinolines via Skeleton-Reorganizing Coupling of Cycloheptatriene and Amines.

Density functional theory calculations were conducted to refine our understanding at the molecular level of the synthesis of fused 1,2-dihydroquinolines through Rh- and acid-catalyzed skeleton-reorganizing coupling reactions of cycloheptatriene with amines. The results reveal that the reaction progresses via cascade catalysis, consisting of consecutive steps of Rh-catalyzed intermolecular coupling involving two Rh III -Rh I -Rh III transformations with a maximum energy barrier of 27.1 kcal/mol, followed by acid-catalyzed intramolecular skeleton reorganization with a peak energy barrier of 23.3 kcal/mol. The most significant finding of this work is the identification of a new oxidation-reduction mode of the Rh center. This mode is achieved via migration of a proton from the ammonium ion to the metal center and nucleophilic attack-induced intermolecular reductive coupling, distinguishing it from the conventional oxidative addition-reductive elimination process. The acid-catalyzed intramolecular skeleton reorganization necessitates the assistance of a second HOTs molecule, along with its conjugate base, which sequentially facilitates retro-Mannich-type C-C cleavage and the isomerization of the terminal imine to enamine via acid-base catalysis. Our calculations also explain why the azabicyclic tropene byproduct does not compete with the formation of the fused 1,2-dihydroquinoline product. These theoretical insights are expected to provide valuable guidance for further improvements in the efficiency of skeleton-reorganizing coupling reactions between cycloheptatriene and amines.