Exploring regioselectivity in 1,3‐dipolar cycloaddition of thioamides, selenoamides, and amides with propadienyl cation derivatives using density functional theory

This study explores the potential mechanisms (Paths 1 and 2) involved in the regioselective dipolar cycloaddition of thioamides, selenoamides, and amides with propargyl alcohol using density functional theory (DFT). Our calculations reveal that the initial step involves the formation of a cation with catalyst. Subsequently, isomerization occurs between cations I and II via 1,3‐hydride transfer in the second step. We analyzed the global reactivity index and frontier molecular orbital (FMO) theory to gain insights into the mechanism. In the third step, chalcoamides attack cations I and II, forming an intermediate. The formation of a five‐member ring intermediate constitutes the fourth step, followed by hydrogen transfer to produce stable five‐member heterazole compounds in the final step. We demonstrated the influence of substituents in the electrophile by employing various electron‐withdrawing and donating groups. Additionally, we examined the effect of the dielectric medium on the reaction barrier using polarizable continuum model. Thus, this study provides valuable insights for the rational design of more efficient 1,3‐dipolar cycloaddition reactions yielding regioselective products.