Theoretical analysis of the regioselectivity of 1,3-dipolar cycloaddition of C-(methoxycarbonyl)-N-methyl with methyl acrylate and vinyl acetate

Mechanism and Regioselectivity of the 1,3-Dipolar Cycloaddition of Methyleneamine N-Oxide with Cyclopent-3-Ene-1,2-Dione and its Aza, Oxa and Thia Analogues: A Dft Approach

“…In this pathway three p z orbitals of the 1,3-dipole and two p z orbitals of the dipolarophile will combine suprafacially which is in agreement with the Woodward -Hoffmann rules [14], and symbolized as [p4s þ p2s]. The 1,3-DC are highly regioselective, stereoselective and stereospecific (syn addition) [4,15]. Fleming explained regioselectivity and reactivity in the 1,3-DC reactions by using frontier molecular orbitals theory (FMO) [16].…”

“…Previous theoretical studies on 1,3-DC reactions showed that the methods including gradient corrections and hybrid functionals for exchange and correlation, such as DFT=B3LYP, together with the standard 6-31G* basis set, yield activation energies in good agreement with experiment [4,15,40]. Thus, in the present study, the quantum chemical calculations have been performed using this methodology.…”

“…We also concluded that the results obtained from energetic and electronic approaches, with the exception of the Gazquez -Mendez rule based on NPA analysis, confirm that 1,5-regioisomer is the major product. Consequently, at least in the 1,3-DC reactions between a nitrone and homo or heterocyclic enes, Houk's rule is capable of predicting the regioselectivity, in contrast to the view of Benchouk and Mekelleche [4] which states ''Houk's rule is not verified for the 1,3-DC reactions of nitrones. ''…”

“…Given their importance, several investigations have been directed toward the determination of their reaction mechanism, but these remain questionable [10,11]. Two types of these reactions have been identified: step-wise and concerted [4]. The concerted pathway, proposed primarily by Huisgen [10,12,13], is a single-step, four-centre cycloaddition and involves 4p electrons from the dipole and 2p electrons from the dipolarophile.…”

“…They have reported, erroneously, the NED mechanism for both these reactions because their results show that the 1,3-DC reaction of 1-phenylethyl nitrone with allyl alcohol must follow the IED mechanism. Benchouk et al [4] studied the regioselectivity of the 1,3-DC reaction of C-(methoxycarbonyl)-N-methyl nitrone with methyl acrylate and vinyl acetate using DFT at the B3LYP=6-31G* level. Their analysis of HOMO -LUMO gaps, chemical potentials and charge transfer at the TSs showed that their studied reactions are categorized as involving NED and IED mechanisms, respectively.…”