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

doi:10.6023/cjoc202603023

摘要/Abstract

在有机合成中, 碳碳双键之间的[2＋2]环加成反应是构筑环丁烷骨架的一类重要合成策略. 其中, 区域选择性与非对映选择性的控制是该类反应的核心问题之一. 采用密度泛函理论计算, 系统研究了噁唑酮类化合物经能量转移激发生成双自由基中间体后, 与烯烃发生加成并最终关环生成环丁烷类产物的反应过程. 计算结果表明, 区域选择性由三重态噁唑酮底物与烯烃的自由基加成步骤决定, 自由基的稳定性在此过程中起着关键作用. 此外, 非对映选择性的控制步骤为自由基-自由基偶联关环过程. 对比分析发现, 非对映选择性由π-π堆积等非共价相互作用与取代基的位阻效应协同控制.

关键词: 自由基偶联, 分步[2＋2]环加成, 密度泛函理论(DFT)计算, 非共价相互作用, 非对映选择性控制

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

引用此文

吕明, 赵博迪, 徐铭昊, 戚孝天. 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[J]. 有机化学, 2026, 46(9): 3731-3736.

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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图/表 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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