Mechanistic insights into the (3 + 2) cycloaddition of azomethine ylide with dimethyl acetylenedicarboxylate bond evolution theory.

The mechanistic pathway of the (3 + 2) cycloaddition (32CA) between azomethine ylide 1 and dimethyl acetylenedicarboxylate 2, affording 4-isoxazoline derivatives, was elucidated Density Functional Theory (DFT) calculations employing the B3LYP-D3 functional and the 6-311++G(d,p) basis set in 1,4-dioxane. Reactivity insights derived from Conceptual DFT (CDFT) demonstrated that compound 1 behaves as an ambiphilic species with significant nucleophilic and electrophilic tendencies, whereas compound 2 functions predominantly as an electrophile. These electronic features reveal a marked polarity in the cycloaddition and align with a forward electron density flux (FEDF) governing the reaction process.