Catalyst-free [3 + 2] cycloaddition reaction of oxa-, aza-, and thio-bicyclic alkenes with cyclic and acyclic nitrones: A mechanistic study

Abstract

The azole heterocyclic compounds and their derivatives have achieved much significance in medicinal chemistry. We present results on the mechanism of [3 + 2] cycloaddition (32CA) reactions of bicyclic alkenes with cyclic and acyclic nitrones to furnish isoxazolines at the M06-2X/6–311++G(d,p) level of theory. A key finding of this study is the preferred formation of the exo cycloadducts over the endo cycloadducts in the reaction of both cyclic and acyclic nitrones to bicyclic alkenes which is in good agreement with the experimental work of Yao et. al. (Org. Chem. Front., 2019, 6, 3360–3364). A one-step asynchronous mechanism of cycloaddition is observed in the titled reaction. Global reactivity parameters describe the significant influence of the electronic nature of the substituent on the flux of electron density between the reagents. Substituents affect the magnitude of the activation barriers but do not change the selectivity of the reactions.