Theoretical Insight towards Mechanism, Role of NHC and DBU in the Synthesis of Substituted Quinolines

Abstract A plausible mechanism for the conversion of aldimine to 2‐phenyl‐4‐difluoromethylquinoline catalyzed by N‐heterocyclic carbene (NHC) in association with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) is investigated in detail by using density functional theory (DFT) method. Six significant stages are proposed to be involved in the whole catalytic cycle, starting from the generation of NHC followed by its nucleophilic interaction with the carbon atom of C‐N in aldimine to generate corresponding aza‐Breslow intermediate. This aza‐Breslow intermediate further undergoes intramolecular umpolung addition followed by several proton transfers to regenerate the NHC along with 2‐phenyl‐4‐difluoromethylquinoline. The role of NHC in this intramolecular umpolung addition of aza‐Breslow intermediate has been investigated by using conceptual DFT. Apart from NHC; the role of DBU in this catalytic cycle has also been monitored carefully. These theoretical findings are in good agreement with experimental results and also provide a deeper insight into the mechanism of NHC catalyzed synthesis of 2‐phenyl‐4‐difluoromethylquinoline.