Mechanistic Insights into the N‐Heterocyclic Carbene Catalyzed Synthesis of α,δ‐Diketones: A DFT Approach

Density functional theory (DFT) has been utilized to understand the mechanism for N‐heterocyclic carbene (NHC) catalyzed synthesis of 1‐(4‐methoxyphenyl)‐2,4‐diphenylbutane‐1,4‐dione from p‐methoxybenzaldehyde and E‐chalcone. Quantum chemical simulations suggest that the catalytic cycle for the formation of α,δ‐diketone commences with nucleophilic interaction of in situ generated active catalyst NHC and p‐methoxybenzaldehyde to form a tetrahedral zwitterionic intermediate, which on subsequent proton transfer reactions result the Breslow intermediate. 1,4‐umpolung addition of Breslow intermediate to E‐chalcone followed by a proton shift facilitates the release of NHC from the catalytic cycle along with the generation of enolic form of the product. Enolic form finally transforms into the desired product under the assistance of both protonated and free 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). Furthermore, conceptual DFT and frontier molecular orbital analyses help to unravel the role NHC in this catalytic cycle. Apart from NHC, protonated and free DBU, existence of advantageous π‐π stacking interaction is also very effective in lowering the activation energy barrier efficiently. A mechanistic profile has been developed for N‐heterocyclic carbene (NHC) catalyzed synthesis of α,δ‐diketone from p‐methoxybenzaldehyde and E‐chalcone using density functional theory (DFT) method. The reaction has been accomplished via umpolung strategy and generated Breslow intermediate served the origin of umpolung strategy. The role of NHC in this catalytic cycle has been explored using conceptual DFT and frontier molecular orbital analyses.