A series of novel spiropyrrolothiazoles with quinoxalines motifs have been synthesized by a four-component 1,3-dipolar cycloaddition reaction of various derivatives of trans-β-nitrostyrene and an azomethine ylide, generated in situ from 1,3-thiazolane-4-carboxylic acid, ninhydrin and 1,2-phenylenediamine. The stereochemistry of the products has been confirmed by single crystal X-ray structure and spectroscopic techniques. Theoretical calculations have been carried out using DFT methods at the B3LYP/6-31G(d,p), wB97xD/6-31G(d,p) and M06-2X/6-31G(d,p) levels. The regio- and stereoselectivity have been explained on the basis of transition state stabilities and global and local reactivity indices of the reactants. The assessment of geometries and energetics of transition states revealed the importance of π/π interactions between aromatic rings in the regioselectivity of the cycloaddition reaction. The B3LYP functional is unable to deal with this weak interaction in the proposed TSs and it leads to an incorrect conclusion about the reaction regioselectivity. In this report, we successfully employed wB97xD and M06-2X functionals to calculate the transition states relative energies.
