AbstractThe [3+2] cycloaddition (32CA) reaction of tomentosin with benzonitrile oxide yielding a spiro‐isoxazoline has been studied within the Molecular Electron Density Theory at the B3LYP/6‐31(d,p) computational level. Given the multifunctionality of tomentosin, this 32CA reaction can take place along 16 competitive reaction paths. The chemo‐, regio‐, and stereoisomeric reaction paths involving the two CC double bonds of tomentosin have been studied. Density functional theory (DFT) calculations account for the total chemo‐ and regioselectivity, in complete agreement with the experimental outcomes, being suggestive of low diastereofacial selectivity. Analysis of the conceptual DFT indices accounts for the nonpolar character of this 32CA reaction. On the other hand, the topological analysis of the electron localization function of the selected points of the intrinsic reaction coordinate associated with the formation of the CC and CO single bonds emphasizes the zw‐type reactivity of the phenyl nitrile oxide; the reaction taking place through a non‐concerted two‐stage one‐step mechanism initialized with the formation of the CC single bond involving the β‐conjugated carbon of tomentosin.