Theoretical Insight into the Mechanisms and Regioselectivity of [4 + 3] and [4 + 1] Annulations of Enals with Azoalkenes Catalyzed by N-Heterocyclic Carbenes.

The reaction mechanisms on the NHC-catalyzed [4 + 3] and [4 + 1] annulations of enals with azoalkenes have been theoretically investigated with the aid of the density functional theory calculations. It is found that the additives play an important role in promoting proton transfer and dehydration. The impacts of catalysts (NHC-A and NHC-B) and substituent groups on the regioselectivity were rationalized. The origin of the regioselectivity involved in these reactions was probed by performing distortion-interaction analysis. For reaction A with NHC-A as the catalyst and Boc group as the substituent, the regioselectivity is predicted to be determined by the interaction energy of 3 with R in TS versus TS. For reaction B with NHC-B as the catalyst and Boc group as the substituent, the unstable boat-type conformation versus the stable chair-type conformation involved in the NHC-B moiety accounts for the regioselectivity. In reaction C with NHC-A as the catalyst and Ts group as the substituent, distortion energies of 3 and R in TS versus TS are found to be the major reason delivering regioselectivity even higher than that of reaction A.