Mechanisms and regioselectivities of DABCO/DMAP‐catalyzed [2+4] annulation reactions of allenoate with α,β‐unsaturated cyclic ketimine: A DFT study

Abstract

AbstractIn the present study, the reaction mechanisms as well as regioselectivities of 1,4‐diazabicyclo‐[2.2.2] octane (DABCO) and 4‐dimethylaminopyridine (DMAP)‐catalyzed [2+4] annulation reactions of allenoate with α,β‐unsaturated cyclic ketimine leading to hydropyridine derivatives have been theoretically investigated using density functional theory (DFT). In general, the amine catalyst can initiate the reaction by nucleophilic attack to allenoate leading to zwitterionic intermediate, which can then react with cyclic ketimine following different reaction mechanisms. For DABCO‐catalyzed annulation, the α‐attack is more energetically favorable, and the subsequent two consecutive proton transfers followed by intramolecular cyclization along with catalyst regeneration can lead to the α,β‐[2+4] cycloadduct. While for DMAP‐catalyzed annulation, γ‐attack is preferred, and the subsequent intramolecular cyclization followed by catalyst regeneration results into the β,γ‐[2+4] cycloadduct. The calculated results are consistent with the experimental observations. Further noncovalent interaction (NCI) analyses reveal that the steric repulsion, hydrogen bond interactions, and intramolecular C─H···π interactions as well as π‐π interactions would be responsible for the observed regioselectivities.