Pd/Xu-Phos催化不对称碳胺化反应合成异噁唑烷的密度泛函理论(DFT)研究

doi:10.6023/cjoc202511004

有机化学 ›› 2026, Vol. 46 ›› Issue (5): 2044-2050.DOI: 10.6023/cjoc202511004 上一篇下一篇

研究论文

Pd/Xu-Phos催化不对称碳胺化反应合成异噁唑烷的密度泛函理论(DFT)研究

石嘉逸^a, 仝文彦^a, 李志铭^a^,^b^,^*(), 王全瑞^a^,^*(), 张俊良^a^,^b^,^c^,^*()

^a 复旦大学化学系上海 200438
^b 复旦大学绿色化学合成与转化技术全国重点实验室上海 200438
^c 中国科学院上海有机化学研究所金属有机化学全国重点实验室上海 200032

收稿日期:2026-01-06 修回日期:2026-02-08 发布日期:2026-02-28
基金资助:
国家自然科学基金(22471042); 国家自然科学基金(22031004); 国家自然科学基金(22271053); 国家自然科学基金(22471040); 上海市科学技术委员会(23ZR1404800); 复旦大学科学智能专项(FudanX24AI024); 上海市教育委员会(20212308); 国家重点研发计划(2021YFF0701600); 复旦大学智能计算(CFFF)平台

A Density Functional Theory (DFT) Study on the Pd/Xu-Phos-Catalyzed Asymmetric Carboamination towards Isoxazolidines

Jiayi Shi^a, Wenyan Tong^a, Zhiming Li^a^,^b^,^*(), Quanrui Wang^a^,^*(), Junliang Zhang^a^,^b^,^c^,^*()

^a Department of Chemistry, Fudan University, Shanghai 200438
^b State Key Laboratory of Green Chemical Synthesis and Conversion, Fudan University, Shanghai 200438
^c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received:2026-01-06 Revised:2026-02-08 Published:2026-02-28
Contact: * E-mail: zmli@fudan.edu.cn; qrwang@fudan.edu.cn; junliangzhang@fudan.edu.cn
Supported by:
National Natural Science Foundation of China(22471042); National Natural Science Foundation of China(22031004); National Natural Science Foundation of China(22271053); National Natural Science Foundation of China(22471040); Science and Technology Commission of Shanghai Municipal(23ZR1404800); AI for Science Foundation of Fudan University(FudanX24AI024); Shanghai Municipal Education Commission(20212308); National Key R&D Program of China(2021YFF0701600); Computing for the Future at Fudan (CFFF) Platform of Fudan University

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摘要/Abstract

采用密度泛函理论(DFT)对Pd/Xu-Phos催化不对称碳胺化反应合成异噁唑烷的反应机理进行了研究. 计算结果表明该反应经历了氧化加成、配体交换、碱介导去质子化、顺式胺钯化和还原消除步骤. 其中碱介导去质子化为反应决速步, 而顺式胺钯化决定了反应的对映选择性. 进一步的形变-相互作用能与结构分析表明, 对映选择性主要来源于顺式胺钯化路径中Xu-Phos-Pd配合物的形变能差异. 此外, 计算还揭示了Xu-Phos配体在催化循环过程中表现出灵活的动态配位方式, 从分子层面解释了实验中观察到的高对映选择性. 该研究从分子层面阐明了Xu-Phos配体的自适应配位行为, 并为不对称催化中手性配体的理性设计提供了重要参考.

关键词: 密度泛函理论(DFT)研究, 钯催化, 不对称碳胺化反应, 异噁唑烷

The mechanism of the Pd/Xu-Phos-catalyzed asymmetric carboamination toward isoxazolidine synthesis was investigated using density functional theory (DFT) calculations. The results indicate that the catalytic cycle proceeds through oxidative addition, ligand exchange, base-mediated deprotonation, cis-aminopalladation, and reductive elimination. Among these elementary steps, base-mediated deprotonation was identified as the rate-determining step, whereas cis-aminopalladation governs the enantioselectivity of the reaction. Further distortion-interaction analysis and structural analyses reveal that the enantioselectivity primarily originates from the distortion-energy difference of the Xu-Phos-Pd complex in the cis-amino-palla- dation path. In addition, the calculations reveal the flexible and dynamic coordination behavior of the Xu-Phos ligand throughout the catalytic cycle, and provide a molecular-level understanding of the high enantioselectivity observed experimentally. This work not only provides deeper insights into the self-adaptive coordination behavior of Xu-Phos ligands, but also offers valuable guidance for the rational design of chiral ligands in asymmetric catalysis.

Key words: density functional theory (DFT) study, palladium-catalysis, asymmetric carboamination, isoxazolidine

引用此文

石嘉逸, 仝文彦, 李志铭, 王全瑞, 张俊良. Pd/Xu-Phos催化不对称碳胺化反应合成异噁唑烷的密度泛函理论(DFT)研究[J]. 有机化学, 2026, 46(5): 2044-2050.

Jiayi Shi, Wenyan Tong, Zhiming Li, Quanrui Wang, Junliang Zhang. A Density Functional Theory (DFT) Study on the Pd/Xu-Phos-Catalyzed Asymmetric Carboamination towards Isoxazolidines[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2044-2050.

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图/表 5

Scheme 1. Palladium/Xu-Phos-catalyzed enantioselective carboamination reaction

Figure 1. Free-energy profiles for oxidative addition, ligand exchange and base-mediated deprotonation (Selected bond distances are shown in black font and in Å unless otherwise noted)

Figure 2. Free-energy profiles for (a) the SN2-type nucleophilic attack along the trans-aminopalladation pathway, and (b) the trans-aminopalladation process (Pink numbers denote NPA charges for selected atoms)

Figure 3. Free-energy profiles for reductive elimination

Figure 4. Comparisons of (S)-TS4 and (R)-TS4 (a) Optimized geometries highlighting H-H contacts; (b) DIA (note that the bar lengths are schematic and not drawn strictly to scale); (c) key dihedral angles.

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Pd/Xu-Phos催化不对称碳胺化反应合成异噁唑烷的密度泛函理论(DFT)研究

A Density Functional Theory (DFT) Study on the Pd/Xu-Phos-Catalyzed Asymmetric Carboamination towards Isoxazolidines

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