Unravelling the Mechanism and Selectivity of the NHC‐catalyzed Three‐Membered Ring‐Opening/Fluorination of Epoxy Enals: A DFT Study

Regio‐ and stereo‐divergent construction of carbon‐fluorine bond remains a challenge in fluorine chemistry, especially reactions involving fluorination at the α‐position of a carbonyl group. Herein, we present a detailed study for predicting the origins of regio‐ and stereo‐selectivity for organocatalyst catalyzed fluorination reaction. Possible mechanisms and origins of selectivities of NHC (N‐heterocyclic carbene)‐catalyzed fluorination reaction of epoxy‐enals were investigated by using DFT (density functional theory) method. The computational results show that the C−F bond formation step determines stereoselectivity and regioselectivity. LP⋅⋅⋅π and C−H⋅⋅⋅F interactions were identified as the main contributors for the stereoselectivity control, in which R‐configured product was preferred. It was found that α‐fluorination is more energetically favorable than γ‐fluorination, which is possibly due to higher reactivity of the α‐carbon; deduced by the local reactivity index analysis. This work would provide valuable insights for predicting origin of the selectivity of fluorination reactions and developing of more effective organocatalyst with high selectivity. In the ring, out the ring: The possible mechanisms and origins of selectivities of NHC (N‐heterocyclic carbene)‐catalyzed fluorination reaction of epoxy enals have been computationally investigated by using DFT (density functional theory). The computational results show that the α‐C−F bond formation step is the rate‐ and selectivity‐determining step and the LP⋅⋅⋅π and C−H⋅⋅⋅F interactions are identified to contribute significantly to control the stereoselectivity, in which the R‐configured product generates preferentially. All the calculated results align well with the experimental observations.