A DFT-based exploration augmented by X-ray and NMR of the stereoselectivity in the 1,3-dipolar cycloaddition of 1-pyrroline-1-oxide to methyl cinnamate and benzylidene acetophenone

A B3LYP/6–31G* study was carried out for the reactions of 1‐pyrroline‐1‐oxide (N1) with methyl cinnamate (E1) and benzylidene acetophenone (E2) for getting a quantitative rationalization of the experimental findings. The product ratios were determined by NMR studies of the crude reaction mixtures. The conformation and stereochemistry of the isolated cycloadducts were finally confirmed by 2D NMR and X‐ray diffraction. The endo/exo‐selectivities were predicted through the computation of activation parameters on the basis of assumed concerted mechanism. The regioselectivity and reactivity were amply predicted by local and global electrophilicity indices and were found to be in good agreement with the experimental findings which were supportive of polar character and of the direction of charge transfer (CT) accompanying the cycloaddition. It was found that the cycloaddition involving methyl cinnamate was endo‐selective, while that with benzylidene acetophenone produced the exo‐isomer as the major adduct. Copyright © 2010 John Wiley & Sons, Ltd. A B3LYP/6‐31G* study has been carried out to calculate the activation parameters, global and local electrophilicity indexes for the cycloaddition of 1‐pyrroline‐1‐oxide with methyl cinnamate and benzylidene acetophenone. Results of theoretical calculations were supported by NMR and X‐Ray diffraction studies.