Insights into N-heterocyclic carbene-catalyzed [3+4] annulation reactions of 2-bromoenals with N-Ts hydrazones

The possible mechanisms and the origin of the stereoselectivity of the N-heterocyclic carbene (NHC)-catalyzed [3 + 4] annulation reaction of 2-bromoenal with N-Ts hydrazone have been investigated using density functional theory (DFT). The general mechanism of NHC-catalyzed debromination of 2-bromoenals has been uncovered in theory for the first time. Our calculated results indicate that the C-C bond formation involved in the stepwise [3 + 4] process is the rate- and stereoselectivity-determining step, and the SR-isomer is the predominant product, which is consistent with the experiment. Non-covalent interaction (NCI) analysis discovers that the strong C-HO and C-H interactions should be the key for controlling the stereoselectivity in the reaction. The local reactivity index analysis shows that the reaction prefers to proceed via the [3 + 4] annulation reaction rather than the [3 + 2] annulation reaction. It is noteworthy that further analysis indicates that the main role of the NHC in this kind of reaction is to activate the C-Br bond, which is different from the umpolung role in the NHC-catalyzed annulation reactions of enals.