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

doi:10.6023/cjoc202511004

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (5): 2044-2050.DOI: 10.6023/cjoc202511004 Previous Articles Next Articles

ARTICLES

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

1. .pdf(713KB)

Abstract

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

Cite this article

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.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 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.

References 37

[1]	Palmer G. C.; Ordy M. J.; Simmons R. D.; Strand J. C.; Radov L. A.; Mullen G. B.; Kinsolving C. R.; Stgeorgiev V.; Mitchell J. T.; Allen S. D. Antimicrob. Agents Chemother. 1989, 33, 895. doi: 10.1128/AAC.33.6.895 pmid: 2764540
[2]	Abe F.; Iwase Y.; Yamauchi T.; Honda K.; Hayashi N. Phytochemistry 1995, 39, 695. doi: 10.1016/0031-9422(95)00034-5
[3]	Lewis J. R. Nat. Prod. Rep. 2001, 18, 95. pmid: 11245403
[4]	Zhu P.; Zhao J.; Yang X.; Zhang H. Chin. J. Org. Chem. 2014, 34, 1167 (in Chinese). doi: 10.6023/cjoc201312029
	(朱培芳, 赵静峰, 羊晓东, 张洪彬, 有机化学, 2014, 34, 1167.) doi: 10.6023/cjoc201312029
[5]	Gao H.; Yu J.; Ge C.; Jiang Q. Molecules 2018, 23, 1440. doi: 10.3390/molecules23061440
[6]	Wolfe J. P. Synlett 2008, 2008, 2913. doi: 10.1055/s-0028-1087339
[7]	Hay M. B.; Wolfe J. P. Angew. Chem., Int. Ed. 2007, 46, 6492. doi: 10.1002/anie.v46:34
[8]	Jiang D.; Peng J.; Chen Y. Tetrahedron 2008, 64, 1641. doi: 10.1016/j.tet.2007.12.014
[9]	Kanemasa S. Synlett 2002, 2002, 1371. doi: 10.1055/s-2002-33506
[10]	Bates R. W.; Nemeth J. A.; Snell R. H. Synthesis 2008, 2008, 1033. doi: 10.1055/s-2008-1066985
[11]	Karyakarte S. D.; Smith T. P.; Chemler S. R. J. Org. Chem. 2012, 77, 7755. doi: 10.1021/jo3013226 pmid: 22870912
[12]	Cornil J.; Guérinot A.; Reymond S.; Cossy J. J. Org. Chem. 2013, 78, 10273. doi: 10.1021/jo401627p pmid: 24028156
[13]	Chen F.; Lai S.; Zhu F.; Meng Q.; Jiang Y.; Yu W.; Han B. ACS Catal. 2018, 8, 8925. doi: 10.1021/acscatal.8b02445
[14]	Ishizuka H.; Adachi K.; Odagi M.; Nagasawa K. Bull. Chem. Soc. Jpn. 2019, 92, 1447. doi: 10.1246/bcsj.20190127
[15]	Zhang L.; Geng R.; Wang Z.; Ren G.; Wen L.; Li M. Green Chem. 2020, 22, 16. doi: 10.1039/C9GC03290H
[16]	Fu X. F.; Zhao W. X. Chin. J. Org. Chem. 2019, 39, 625 (in Chinese). doi: 10.6023/cjoc201808031
	(付晓飞, 赵文献, 有机化学, 2019, 39, 625.) doi: 10.6023/cjoc201808031
[17]	LaLonde R. L.; Wang Z.; Mba M.; Lackner A. D.; Toste F. D. Angew. Chem., Int. Ed. 2010, 49, 598.
[18]	Dongol K. G.; Tay B. Y. Tetrahedron Lett. 2006, 47, 927. doi: 10.1016/j.tetlet.2005.11.148
[19]	Peng J.; Jiang D.; Lin W.; Chen Y. Org. Biomol. Chem. 2007, 5, 1391. doi: 10.1039/B701509G
[20]	Peng J.; Lin W.; Yuan S.; Chen Y. J. Org. Chem. 2007, 72, 3145. doi: 10.1021/jo0625958
[21]	Lemen G. S.; Giampietro N. C.; Hay M. B.; Wolfe J. P. J. Org. Chem. 2009, 74, 2533. doi: 10.1021/jo8027399
[22]	Liu S.; Fang D. J. Org. Chem. 2023, 88, 14540. doi: 10.1021/acs.joc.3c01561
[23]	Ye X.; Liu G.; Popp B. V.; Stahl S. S. J. Org. Chem. 2011, 76, 1031. doi: 10.1021/jo102338a
[24]	Spadafora B. P.; Ribeiro F. W. M.; Matsushima J. E.; Ariga E. M.; Omari I.; Soares P. M. A.; de Oliveira-Silva D.; Vinhato E.; McIndoe J. S.; Correra T. C.; Rodrigues A. Org. Biomol. Chem. 2021, 19, 5595. doi: 10.1039/d1ob00670c pmid: 34096563
[25]	Liu Z.; Wang Y.; Wang Z.; Zeng T.; Liu P.; Engle K. M. J. Am. Chem. Soc. 2017, 139, 11261. doi: 10.1021/jacs.7b06520
[26]	Ni H. Q.; Kevlishvili I.; Bedekar P. G.; Barber J. S.; Yang S.; Tran-Dubé M.; Romine A. M.; Lu H.; McAlpine I. J.; Liu P.; Engle K. M. Nat. Commun. 2020, 11, 6432. doi: 10.1038/s41467-020-20182-4
[27]	Yang Z.; Wang Q.; Zhuo S.; Xu L. J. Org. Chem. 2020, 85, 6981. doi: 10.1021/acs.joc.0c00296
[28]	Yang F.; Bin H.; Zhao F.; Cheng L.; Wang H.; Xie J. H. Org. Lett. 2025, 27, 4244. doi: 10.1021/acs.orglett.5c00931
[29]	Zhou Y.; Shang Z.; Li R.; Xu X. Org. Chem. Front. 2018, 5, 3256. doi: 10.1039/C8QO00925B
[30]	Wang Y.; Wang L.; Chen M.; Tu Y.; Liu Y.; Zhang J. Chem. Sci. 2021, 12, 8241. doi: 10.1039/D1SC01337H
[31]	Feng J.; Shi J.; Wei L.; Liu M.; Li Z.; Xiao Y.; Zhang J. Angew. Chem. Int., Ed. 2023, 62, e202215407.
[32]	Frisch M. J.; Trucks G. W.; Schlegel H. B.; Scuseria G. E.; Robb M. A.; Cheeseman J. R.; Scalmani G.; Barone V.; Petersson G. A.; Nakatsuji H.; Li X.; Caricato M.; Marenich A. V.; Bloino J.; Janesko B. G.; Gomperts R.; Mennucci B.; Hratchian H. P.; Ortiz J. V.; Izmaylov A. F.; Sonnenberg J. L.; Williams; Ding F.; Lipparini F.; Egidi F.; Goings J.; Peng B.; Petrone A.; Henderson T.; Ranasinghe D.; Zakrzewski V. G.; Gao J.; Rega N.; Zheng G.; Liang W.; Hada M.; Ehara M.; Toyota K.; Fukuda R.; Hasegawa J.; Ishida M.; Nakajima T.; Honda Y.; Kitao O.; Nakai H.; Vreven T.; Throssell K.; Montgomery Jr., J. A.; Peralta J. E.; Ogliaro F.; Bearpark M. J.; Heyd J. J.; Brothers E. N.; Kudin K. N.; Staroverov V. N.; Keith T. A.; Kobayashi R.; Normand J.; Raghavachari K.; Rendell A. P.; Burant J. C.; Iyengar S. S.; Tomasi J.; Cossi M.; Millam J. M.; Klene M.; Adamo C.; Cammi R.; Ochterski J. W.; Martin R. L.; Morokuma K.; Farkas O.; Foresman J. B.; Fox D. J. Gaussian 09, Revision E.01, Wallingford, CT, 2016.
[33]	Glendening E. D.; Landis C. R.; Weinhold F. J. Comput. Chem. 2013, 34, 1429. doi: 10.1002/jcc.23266 pmid: 23483590
[34]	Simmons H. E.; Williams J. K. J. Am. Chem. Soc. 1964, 86, 3222. doi: 10.1021/ja01070a004
[35]	Williams D. E.; Craycroft D. J. J. Phys. Chem. 1987, 91, 6365. doi: 10.1021/j100309a011
[36]	Springborg M. Europhys. Lett. 1990, 11, 325. doi: 10.1209/0295-5075/11/4/006
[37]	Bickelhaupt F. M.; Houk K. N. Angew. Chem., Int. Ed. 2017, 56, 10070. doi: 10.1002/anie.v56.34

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

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 37

Related Articles 9

Recommended Articles

Metrics

Comments

[1]	Qian Zhang, Yaolu Ying, Hongyin Zhang, Linbo Xu, Xinkui Lin, Xiaolei Huang. Palladium-Catalyzed Reductive Cross-Coupling of Propargyl Acetates with Aryl Iodides Involving the Insertion of SO₂ [J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 2033-2040.
[2]	Xinwei Zhang, Shuizhen Lin, Xiaolei Huang. Pd-Catalyzed Reductive Cross-Coupling of Allylic Esters with Aryl Iodides Involving the Insertion of SO₂ [J]. Chinese Journal of Organic Chemistry, 2024, 44(11): 3456-3466.
[3]	Xianqiang Meng, Yi Yang, Wanjie Liang, Jingtao Wang, Rongkui Zhang, Hui Liu. Palladium-Catalyzed Regioselective Aryl Phenoxylation of Allenamide [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 224-231.
[4]	Meijiao Sun, Jing Tan, Yu Tan, Jinsong Peng, Chunxia Chen. Pd-Catalyzed C(2)—H Arylation of 3-(2-Aminopyrimidin-4-yl)indoles [J]. Chinese Journal of Organic Chemistry, 2023, 43(11): 3945-3959.
[5]	Xiaoying Li, Peihe Li, Zheng Wang, Hui Fu, Qipu Dai. Palladium-Catalyzed Intramolecular Decarboxylative Allylic Amination of Aroyloxycarbamates [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3089-3096.
[6]	Li Huang, Yuhao Wang, Jiying Liu, Shijun Li, Wenjing Zhang, Yu Lan. Mechanistic Study of Cu-Catalyzed Addition Reaction of lsocyanates [J]. Chinese Journal of Organic Chemistry, 2021, 41(11): 4347-4352.
[7]	Li Yingjun, Zhao Yue, Jin Kun, Gao Lixin, Sheng Li, Liu Xuejie, Yang Hongjing, Lin Ledi, Li Jia. Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity [J]. Chin. J. Org. Chem., 2019, 39(9): 2599-2608.
[8]	LI, Xiao-Liu* ; WANG, Yan-Po; CHEN, Hua; LI, Zhi-Wei; XING, Chun-Yong. Microwave Assisted 1,3-Dipolar Cycloaddition Reaction of exo-Glucal with Nitrone [J]. Chin. J. Org. Chem., 2008, 28(10): 1750-1755.
[9]	JIANG, Hong ^a; MA, Fang-Fang ^a; XIE, Xiao-Min^a ; ZHANG, Zhao-Guo^*,a,b. Application of Bulky and Electron-Rich MOP-Type Phosphine Ligands in Palladium-Catalyzed α-Arylation of 1,3-Dicarbonyl Compounds [J]. Chin. J. Org. Chem., 2008, 28(08): 1410-1415.