The mechanism, regio-, chemo-, diastereo-, stereo- and enantio-selectivity of the [3 + 2] cycloaddition reaction of aryl nitrile oxides with 5-acetoxy-2(5H)-furanone has been performed by means of several computational approaches, namely, activation and reaction energies, global electron density transfer (GEDT), DFT reactivity indices and rate constants. The titled reaction leads to formation of 2-isoxalines which are important intermediates for the construction of many synthetically important cycloadducts. The calculations were performed using hybrid density functionals M06-2X, B3LYP and MPWB1K together with split valence triple zeta basis set 6-311++ G(d,p). Chemo- and regio-selectivity is not affected by the nature of substituent on the aryl nitrile oxides. IRC calculations and activation energies show that this reaction follows an asynchronous concerted mechanism. Analysis of the electrophilic P-A(+) and nucleophilic P-A(-) Parr functions at the different reaction sites in the 5-acetoxy-2(5H)-furanone indicates that the aryl nitrile oxides add across the atomic centers with the highest Mulliken atomic spin densities. The results reported herein are in good agreement with previous experimental works. The GEDT calculations unravel the low polar character of the [3 + 2] cycloaddition reactions. Overall, the viability of these [3 + 2] cycloaddition reactions depends on the low polar character, which also depends on the electrophilic and nucleophilic character of the reacting 5-acetoxy-2(5H)-furanone and aryl nitrile oxides, respectively.