Insights into the Halogen Effects on Regioselectivities of Nucleophilic Haloalkylation of <i>α</i>,<i>β</i>‐Enones

The halogen effects, specifically the replacement of chlorine with fluorine, on the shift in regioselectivity from 1,4- to 1,2-addition in the nucleophilic haloalkylation of α,β-enones have been investigated using density functional theory (DFT) calculations. Computational analysis revealed that the difluorocarbanion PhSO₂CF₂ ^-, being a hard nucleophile with lower energy of the highest occupied molecular orbital (HOMO), selectively undergoes 1,2-addition of chalcone, primarily dominated by Coulombic interactions. In contrast, the nucleophilic 1,4-addition of chalcone by a soft dichlorocarbanion PhSO₂CCl₂ ^- is controlled by frontier molecular orbital interactions. This work provides a deep understanding of the regioselective control in nucleophilic haloalkylation reactions.