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

doi:10.6023/cjoc202603023

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (9): 3731-3736.DOI: 10.6023/cjoc202603023 Previous Articles Next Articles

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非共价相互作用对噁唑酮与烯烃分步[2＋2]环加成反应非对映选择性的调控效果研究

吕明^†, 赵博迪^†, 徐铭昊, 戚孝天^*()

武汉大学化学与分子科学学院武汉 430072

收稿日期:2026-03-19 修回日期:2026-04-09 发布日期:2026-05-07
通讯作者: 戚孝天
作者简介:
^† 共同第一作者.
基金资助:
国家自然科学基金(22571241); 及武汉大学超算中心超算系统资助项目.

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

Ming Lü, Bodi Zhao, Minghao Xu, Xiaotian Qi^*()

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072

Received:2026-03-19 Revised:2026-04-09 Published:2026-05-07
Contact: Xiaotian Qi
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
^† The authors contributed equally to this work
Supported by:
National Natural Science Foundation of China(22571241); Supercomputing System in the Supercomputing Center of Wuhan University.

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Abstract

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.

Key words: radical coupling, stepwise [2＋2] cycloaddition, density functional theory (DFT) calculation, non-covalent interactions, diastereoselectivity control

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Ming Lü, Bodi Zhao, Minghao Xu, Xiaotian Qi. Diastereoselectivity Control in Stepwise [2＋2] Cycloadditions of Oxazolones with Alkenes: A Theoretical Study of Non-covalent Interactions[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3731-3736.

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Fig. & Tab. 5

Scheme 1. Photocatalytic [2＋2] cycloaddition reactions

Figure 1. Free energy profile for the radical addition between oxazolone 1 and methylstyrene All energies were calculated at M06-2X/6-311＋G(d,p)/SMD (dichloromethane) level of theory.

Figure 2. Free energy profile of the [2＋2] cycloaddition of oxazolone 1 with methylstyrene All energies were calculated at M06-2X/6-311＋G(d,p)/SMD (dichloromethane) level of theory.

Figure 3. (a) Free energy profile of the [2＋2] cycloaddition of oxazolone 1 with 1-hexene (All energies were calculated at M06-2X/6-311＋G(d,p)/SMD (acetone) level of theory); (b) Free energy profile of the [2＋2] cycloaddition of oxazolone 2 with 1-hexene (All energies were calculated at M06-2X/6-311＋G(d,p)/SMD (acetonitrile) level of theory); (c) Three-dimensional structure of the radical-radical coupling transition state

Figure 4. NCI analysis of the radical-radical cross-coupling transition states

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非共价相互作用对噁唑酮与烯烃分步[2＋2]环加成反应非对映选择性的调控效果研究

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

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