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 R2′ in TS3A versus TS8A. 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 R2′ in TS3C versus TS6C are found to be the major reason delivering regioselectivity
even higher than that of reaction A.