Mechanistic Investigation on an NHC‐Catalyzed [3 + 3] Annulation of 2‐Bromoenals with <i>β</i> ‐Oxodithioester: Mechanism, Origins of Stereoselectivity

An increasing number of studies have demonstrated the cooperative use of chiral N‐heterocyclic carbenes (NHCs) and Lewis acid to enhance catalytic efficiency in stereoselective annulation reactions. Herein, molecular‐level insights into the NHC‐catalyzed [3 + 3] annulation of 2‐bromoenals with β ‐oxodithioester are elucidated through density functional theory calculations. The reaction proceeds via multiple key steps: formation of the Breslow intermediate, CBr bond cleavage, α ‐protonation generating α , β ‐unsaturated acylazolium, stereoselective Si‐face addition between the acylazolium and LiCl‐coordinated β ‐oxodithioester, intramolecular proton transfer, and catalyst regeneration. The stereoselectivity‐determining CC bond formation step exhibits enhanced facial control through cooperative effects. Noncovalent interaction (NCI) and atoms‐in‐molecules analyses reveal that hydrogen‐bond networks, LP··· π , and O···S interactions preferentially stabilize the RS ‐configured isomer. Notably, LiCl plays dual roles: (1) it amplifies stereocontrol by facilitating multiple NCIs during the CC bond formation, and (2) reduces transition‐state polarity through solvent–solute interactions, thereby lowering the activation barrier. The work deepens the understanding of how Lewis acid additive modulate both electronic and steric landscapes in NHC catalysis, offering valuable insights for stereocontrolled annulation reactions.