Insights into N-Heterocyclic Carbene-Catalyzed [4+2] Annulation Reaction of Enals with Nitroalkenes: Mechanisms, Origin of Chemo- and Stereoselectivity, and Role of Catalyst

In this paper, density functional theory (DFT) calculations have been employed to investigate the detailed mechanisms, origin of chemo‐ and stereoselectivity, and role of catalyst for the reaction of enals with nitroalkenes catalyzed by N‐heterocyclic carbenes (NHCs). The calculated results disclose that the reaction contains seven steps, that is, the nucleophilic attack on the α, β‐unsaturated aldehyde by NHC, the [1, 2]‐proton transfer for the formation of Breslow intermediate, the β‐protonation for affording enolate intermediate, the nucleophilic addition on the Re/Si face of enolate by the nitroalkenes, the [1, 5] proton transfer, the ring‐closure process, and the regeneration of NHC. The addition on the Re/Si face of enolate is identified to be the stereocontrolling step, in which the chiral centers including α‐carbon of enals and β‐carbon of nitroalkenes are formed. Moreover, the reaction pathway leading to the RR‐configured product has the lowest Gibbs free energy barrier, which is in agreement with the experimental observation. Furthermore, the analyses of electrophilic and nucleophilic Parr functions and global reactivity indices (GRIs) have been performed to explore the origin of chemoselectivity and the role of catalyst. This theoretical work would provide valuable insights for the rational design of more effective organocatalyst for this kind of reactions with high stereoselectivities. Enriching our understanding: The detailed mechanism as well as chemo‐ and stereoselectivity of the NHC‐catalyzed [4+2] annulation reaction for the formation of enantioenriched coumarins have been investigated using the DFT method.