Mechanism and origin of stereoselectivity in an NHC-catalyzed [4 + 2] annulation between an activated ester and a...

N-heterocyclic carbene (NHC) organocatalysis has emerged as a sustainable platform for constructing enantioenriched boronated frameworks, yet the mechanism and origin of stereoselectivity on NHC-catalyzed [4 + 2] annulation between an activated ester and a β-borate enone to furnish a chiral β-borate δ-lactone remain elusive. Herein, we report a comprehensive density functional theory (DFT) study to systematically unravel the mechanism and the origin of stereoselectivity of this transformation. Based on the computational results, the most energetically favorable pathway proceeds via five elementary steps: nucleophilic addition of NHC to the carbonyl carbon of the ester, cleavage of the C-O bond, α-H elimination, [4 + 2] annulation, and regeneration of the NHC catalyst. The [4 + 2] cycloaddition step determines the stereoselectivity, preferentially furnishing the RS-configured isomer as the dominant product. Combined noncovalent interaction (NCI) and atoms-in-molecules (AIM) analyses reveal that multiple stabilizing noncovalent interactions, such as C-H⋯π, LP⋯π, and hydrogen bond interactions, collectively lower the energy barrier of the RS-configured transition state. This computational work enhances the mechanistic understanding of the NHC-catalyzed synthesis of chiral β-boryl δ-lactones and provides theoretical guidelines for the rational design of enantioenriched organoboranes.