Diastereoselectivity Control in Stepwise [2＋2] Cycloadditions of Oxazolones with Alkenes: A Theoretical Study of Non-covalent Interactions

In organic synthesis, the construction of cyclobutane scaffolds via [2＋2] cycloaddition represents an important synthetic strategy.Among these transformations, controlling regioselectivity and diastereoselectivity is one of the core issues.In this work, density functional theory (DFT) calculations were employed to investigate the reaction mechanism in which oxazolones, upon excitation via energy transfer, generate a triplet biradical intermediate that undergoes addition to alkenes and subsequent cyclization to yield cyclobutane products.The computational results indicate that the regioselectivity is determined by the radical addition step between the triplet oxazolone substrate and the alkene, with radical stability playing a key regulatory role in this process.Furthermore, the diastereoselectivity is controlled during the radical-radical coupling cyclization step.It is found that the diastereoselectivity is synergistically governed by non-covalent interactions such as π-π stacking and the steric effects of substituents.