The regioselective radical CH trifluoromethylation of aromatic compounds have been shown to proceed in good yield and high regioselectivity when cyclodextrin (CD) is present. Yet, the reaction mechanism and the role of CD during the reaction have remained obscure. To this end, here we performed density functional theory (DFT) calculations to the conformations obtained by semiempirical quantum mechanical molecular dynamics calculations to reveal the reaction mechanism and the role of CD in controlling regioselectivity. The results show that metal salt increases the yield but do not affect the regioselectivity, which we further confirmed by an experiment. In contrast, multiple CD‐substrate complex conformations and reaction pathways were obtained, and CD was shown to contribute to improving the regioselectivity by stabilizing the intermediate state via encapsulation. The present study indicates that CDs can increase the regioselectivity by stabilizing the intermediate and product states while only marginally affecting the transition state.

中文翻译：

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环糊精在芳香族化合物区域选择性自由基CH三氟甲基化中作用的机理研究


当环糊精（CD）存在时，芳香族化合物的区域选择性自由基C-H三氟甲基化反应以良好的收率和高区域选择性进行。然而，反应机制和CD在反应过程中的作用仍然不清楚。为此，我们对半经验量子力学分子动力学计算得到的构象进行了密度泛函理论（DFT）计算，以揭示反应机理以及CD在控制区域选择性中的作用。结果表明，金属盐提高了收率，但不影响区域选择性，我们通过实验进一步证实了这一点。相比之下，获得了多种CD-底物复合物构象和反应途径，并且CD被证明有助于通过封装稳定中间态来提高区域选择性。本研究表明，CD 可以通过稳定中间体和产物态来提高区域选择性，同时仅对过渡态产生轻微影响。