Computational Investigation of Mechanism and Selectivity in (3+2) Cycloaddition Reactions Involving Azaoxyallyl Cations

Azaoxyallyl cations, as novel and versatile three-atom components, have been widely utilized in cycloaddition reactions, with the competition between O- and N-cyclization pathways remaining a key research focus. This study investigates the mechanism and site selectivity of (3+2) cycloaddition between azaoxyallyl cations and 1,2-benzisoxazoles using density functional theory calculations. The results reveal a stepwise (3+2) addition to the C=N double bond, followed by base-assisted N-O bond cleavage and isoxazole ring-opening, leading to oxazoline (via O-cyclization) or imidazolone (via N-cyclization) derivatives. When unsubstituted 1,2-benzisoxazole is used as the substrate, O-cyclization dominates as a kinetically controlled process due to lower activation barriers, while N-cyclization, as a thermodynamically controlled process, is minor. The presence of a methyl group at the C(3) position in 1,2-benzisoxazoles completely blocks N-O bond cleavage, forcing exclusive (3+2) cycloaddition to yield less stable tricyclic products via N-cyclization rather than O-cyclization. These findings align with experimental observations and provide new mechanistic insights into the site selectivity of azaoxyallyl cation cycloadditions.