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DOI: https://doi.org/10.6023/A26070238

研究论文

钯催化Heck偶联直接构建烯丙基CF3全碳季碳中心

  • 马培棪 ,
  • 温涌顺 ,
  • 张仪海 ,
  • 罗文俊 ,
  • 龙礼鹏 ,
  • 陈正旺 ,
  • 唐绍彬 ,
  • 彭湘君 ,
  • 于道鸿
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  • a赣南师范大学 化学与材料学院 合成药物化学江西省重点实验室 赣州 341000;
    b赣南医科大学 药学院心脑血管疾病防治教育部重点实验室 赣州 341000

收稿日期: 2026-07-08

  网络出版日期: 2026-09-07

基金资助

国家自然科学基金 (22461002, 22261004), 江西省自然科学基金 (20232BCJ25050, 20243BCE51174, 20242BAB20110, 20244BAB28057), 先进氟氮材料全国重点实验室 (2026PT0005).

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Palladium-Catalyzed Interrupted Heck Reaction for Direct Access to Allylic CF3-Substituted All-Carbon Quaternary Centers

  • Ma Pei-Yan ,
  • Wen Yongshun ,
  • Zhang Yi-Hai ,
  • Luo Wenjun ,
  • Long Lipeng ,
  • Chen Zhengwang ,
  • Tang Shaobin ,
  • Peng Xiangjun ,
  • Yu Daohong
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  • aJiangxi Province Key Laboratory of Synthetic Pharmaceutical Chemistry, College of Chemistry and Materials Science, Gannan Normal University, Ganzhou, 341000, China;
    bKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, School of Pharmaceutical Sciences of Gannan Medical University, Ganzhou, 341000, China

Received date: 2026-07-08

  Online published: 2026-09-07

Supported by

National Natural Science Foundation of China (22461002, 22261004), Natural Science Foundation of Jiangxi Province (20232BCJ25050, 20243BCE51174, 20242BAB20110, 20244BAB28057), the State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials (2026PT0005).

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摘要

在有机合成领域,由于大位阻的影响,三氟甲基全碳季碳中心的构建一直面临很大的挑战。利用三氟甲基三取代烯烃为原料,通过钯催化的Heck偶联反应,成功发展了一种构建三氟甲基全碳季碳中心的新方法。该方法区域专一性地发生5-exo型的环化反应,没有观察到6-endo型产物的形成。该反应可以兼容卤素、酯基、烯烃、胺、醚和硝基等官能团,吸电子和给电子基团也可被兼容。此外,本研究首次实现了含烯丙基三氟甲基季碳中心的吲哚啉衍生物的构建。

关键词： 三氟甲基全碳季碳中心; 钯催化; 吲哚啉; Heck 反应; 三氟甲基

本文引用格式

马培棪 , 温涌顺 , 张仪海 , 罗文俊 , 龙礼鹏 , 陈正旺 , 唐绍彬 , 彭湘君 , 于道鸿 . 钯催化Heck偶联直接构建烯丙基CF3全碳季碳中心[J]. 化学学报, 0 : 26070238 -26070238 . DOI: 10.6023/A26070238

Abstract

The construction of trifluoromethyl all-carbon quaternary centers is a significant challenge in organic synthesis. We report a palladium-catalyzed, interrupted Heck reaction that directly forges challenging allylic CF3-all-carbon quaternary centers from trisubstituted-alkene with a CF3 group. It provides the first general access to C3-functionalized indolines bearing an allylic CF₃-quaternary center. This method is highly selective, yielding exclusively the 5-exo-trig cyclized product and no 6-endo-trig isomers. Substrates bearing electron-donating or -withdrawing groups were compatible. This reaction tolerated a wide range of functional groups, including ester, nitro, halides (Cl, Br), ether, allyl, amine, amide, heterocycles. The N-protecting group in the substrate have an important effect on the reaction efficiency, in which acetyl group is the optimal choice. This reaction was sensitive for steric hindrance. When the ortho-bromo aniline in substrate 3 was replaced with an ortho-benzylamine, the regioselectivity was completely altered, yielding only the 7-endo-trig cyclization product 5 with no observed 6-exo-trig product. Further transformation of products was carried out. Unexpected deacylation-Pd-catalyzed C-N coupling product was obtained using strong base potassium tert-butoxide; instead, Pd-catalyzed Heck-coupling product was isolated using weaker Cs2CO3 as a base. Control experiments indicated that the diacylation occurred only in the presence of potassium tert-butoxide. Stochiometric reaction of 3a with Pd(PPh3)4 did give the oxidative addition palladium intermediate, instead, product 4a was obtained in 50% yield, which indicated that the rate of 5-exo intramolecular Heck cyclisation and subsequent β-H elimination is so fast that we did not isolate Ar-Pd-Br complex. Accordingly, added Pd(MeCN)2Cl2 (10 mol%), BINAP (10 mol%), Cs2CO3 (0.2 mmol) were introduced into an oven-dried Schlenk tube (10 mL) under N2 atmosphere. Dried THF (2 mL) and (Z)-N-(2-bromophenyl)-N-(2-(trifluoromethyl)but-2-en-1-yl) acetamide (0.2 mmol) were added via syringe. The reaction mixture was stirred at 100 °C in oil bath for 12 h. The mixture was then cooled to room temperature, filtered with celite and washed with ethyl acetate. The solvent was removed under reduced pressure. The crude product was purified by flash column chromatography on silica gel (PE/EA = 10:1 to 5:1) to afford the desired products 4.

Key words： trifluoromethyl all-carbon quaternary centers; palladium catalysis; indoline; Heck reaction; trifluoromethyl

参考文献

[1] (a) Ling, T.; Rivas, F.,Tetrahedron 2016, 72, 6729-6777; (b) Ling, T.; Garfias, J. M.; Lawson, S. L.; Rivas, F.,Tetrahedron 2025, 183, 134711;(c) Ziqi Zhu, L. Y., Yi Wu, Ziqi Guo, Feng Shi, Acta Chim. Sin. 2025, 83, 1465-1471.
[2] (a) Müller, K.; Faeh, C.; Diederich, F.,Science 2007, 317, 1881-1886; (b) Hagmann, W. K., J. Med. Chem. 2008, 51, 4359-4369; (c) Lowe, P. T.; O’Hagan, D., J. Fluorine Chem. 2020, 230, 109420; (d) Uneyama, K., Organofluorine Chemistry. Blackwell: Oxford, 2007.
[3] (a) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V.,Chem. Soc. Rev. 2008, 37, 320-330; (b) Strachan G. J.; Górecka E.; Hobbs J.; Pociecha, D., J. Am. Chem. Soc. 2025, 147,6058-6066; (c) Ogawa, Y.; Tokunaga, E.; Kobayashi, O.; Hirai, K.; Shibata, N.,iScience 2020, 23;(d) Wang, Q.; Song, H.; Wang, Q., Chin. Chem. Lett. 2022, 33, 626-642; (e) Berger, R.; Resnati, G.; Metrangolo, P.; Weber, E.; Hulliger, J., Chem. Soc. Rev. 2011, 40, 3496-3508.
[4] (a) Priyanka, C.; Adepu, R.; Punna, N.,Eur. J. Org. Chem. 2025, 28, e202401168;(b) Nagababu, C.; Prudhviraj, J.; Punna, N., Adv. Synth. Catal. 2023, 365, 8-12.
[5] (a) Hirano, K.,Synthesis 2022, 54, 3708-3718; (b) Wang S.; Wang, W., Chin. J. Org. Chem. 2020, 40,1901-1911; (c) Deng, Q.-H.; Wadepohl, H.; Gade, L. H.,J. Am. Chem. Soc. 2012, 134, 10769-10772;(d) Gao, J.-R.; Wu, H.; Xiang, B.; Yu, W.-B.; Han, L.; Jia, Y.-X., J. Am. Chem. Soc. 2013, 135, 2983-2986; (e) Woźniak, Ł.; Murphy, J. J.; Melchiorre, P., J. Am. Chem. Soc. 2015, 137, 5678-5681; (f) Chen, S.-J.; Chen, G.-S.; Zhang, J.-W.; Li, Z.-D.; Zhao, Y.-L.; Liu, Y.-L., Org. Chem. Front. 2020, 7, 3399-3405; (g) Chen, Y.-X.; Wang, Z.-J.; Xiao, J.-A.; Chen, K.; Xiang, H.-Y.; Yang, H., Org. Lett. 2021, 23, 6558-6562.
[6] (a) Kazmaier, U., Springer Berlin Heidelberg: Berlin, Heidelberg, 2012; p 1-63; (b) Butt, N. A.; Zhang, W., Chem. Soc. Rev. 2015, 44, 7929-7967;(c) Kim, M.; Kim, G.; Kim, D.; Lee, J. H.; Cho, S. H., Beilstein J. Org. Chem. 2025, 21, 639-658; (d) Ding, C.-H.; Hou, X.-L., Transition Metal-Catalyzed Asymmetric Allylation. In Asymmetric Catalysis from a Chinese Perspective, Ma, S., Ed. Springer Berlin Heidelberg: Berlin, Heidelberg, 2011; pp 247-285; (e) A: Show Case of the Most Effective Chiral Ferrocene Ligands in Various Catalytic Reactions. In Chiral Ferrocenes in Asymmetric Catalysis, Dai, L.-X.; Hou, X.-L., Eds. 2009; pp 369-396.
[7] (a) Kitazume, T.; Ishikawa, N.,Chem. Lett. 1982, 11, 137-140; (b) Kitazume T.; Ishikawa, N., J. Am. Chem. Soc. 1985, 107,5186-5191; (c) Furukawa, T.; Nishimine, T.; Tokunaga, E.; Hasegawa, K.; Shiro, M.; Shibata, N.,Org. Lett. 2011, 13, 3972-3975;(d) Wu, J.; Wu, H.; Li, X.; Liu, X.; Zhao, Q.; Huang, G.; Zhang, C., Angew. Chem. Int. Ed. 2021, 60, 20376-20382; (e) Nursahedova, S. K.; Zerov, A. V.; Boyarskaya, I. A.; Grinenko, E. V.; Nenajdenko, V. G.; Vasilyev, A. V., Org. Biomol. Chem. 2019, 17, 1215-1224; (f) Briand, M.; Thai, L. D.; Bourdreux, F.; Vanthuyne, N.; Moreau, X.; Magnier, E.; Anselmi, E.; Dagousset, G., Org. Lett. 2022, 24, 9375-9380.
[8] (a) Li, Y.; Liang, F.; Li, Q.; Xu, Y.-c.; Wang, Q.-R.; Jiang, L.,Org. Lett. 2011, 13, 6082-6085; (b) Trost, B. M.; Gholami, H.; Zell, D.,J. Am. Chem. Soc. 2019, 141, 11446-11451.
[9] Holmes M.; Nguyen K. D.; Schwartz L. A.; Luong T.; Krische M. J.,J. Am. Chem. Soc. 2017, 139, 8114-8117.
[10] Yu Y.-J.; Schäfer M.; Daniliuc C. G.; Gilmour R.,Angew. Chem. Int. Ed. 2023, 62, e202214906.
[11] Zhang Y.; Raugh N.; Koert U.,Org. Lett. 2023, 25, 5641-5645.
[12] (a) Wei, H.; Li, B.; Wang, N.; Ma, Y.; Yu, J.; Wang, X.; Su, J.; Liu, D., ChemistryOpen 2023, 12, e202200235;(b) Silva, T. S.; Rodrigues, M. T.; Santos, H.; Zeoly, L. A.; Almeida, W. P.; Barcelos, R. C.; Gomes, R. C.; Fernandes, F. S.; Coelho, F., Tetrahedron 2019, 75, 2063-2097; (c) Rago, A. J.; Dong, G.,Green Synth. Catal. 2021, 2, 216-227;(d) Liu, D.; Zhao, G.; Xiang, L., Eur. J. Org. Chem. 2010, 2010, 3975-3984.
[13] Katayev D.; Kajita H.; Togni A.,Chem. Eur. J. 2017, 23, 8353-8357.
[14] (a) Bai, X.; Wu, C.; Ge, S.; Lu, Y.,Angew. Chem. Int. Ed. 2020, 59, 2764-2768; (b) Sihag, N.; Bhartiya, H.; Jain, S.; Singh, J.; Reddy, S. R.; Yadav, M. R.,Chem. Commun. 2025, 61, 11413-11416.
[15] (a) Sharma, R.; Sihag, N.; Gupta, P.; Manna, K.; Yadav, M. R.,Chem. Commun. 2025, 61, 7273-7276; (b) Shaw, R.; Sihag, N.; Jain, S.; Sharma, R.; Yadav, M. R.,J. Org. Chem. 2023, 88, 5652-5660.
[16] (a) Xu, B.; Wang, Q.; Fang, C.; Zhang, Z.-M.; Zhang, J.,Chem. Soc. Rev. 2024, 53, 883-971; (b) Burns B.; Grigg R.; Ratananukul P.; Sridharan V.; Stevenson P.; Worakun, T., Tetrahedron Lett. 1988, 29,4329-4332; (c) Grigg, R.; Sridharan, V.; Sukirthalingam, S.; Worakun, T.,Tetrahedron Lett. 1989, 30, 1139-1142;(d) Newman, S. G.; Howell, J. K.; Nicolaus, N.; Lautens, M., J. Am. Chem. Soc. 2011, 133, 14916-14919; (e) Liu, T.; Yao, T.; Fang, R.; Qin, X., ACS Catal. 2025, 15, 7191-7200; (f) Yang, H.; Fan, R.; Wen, D.; Fan, M.; Fang, W., Chin. J. Chem . 2024, 42, 2459-2465; (g) Zhou, L.; Ma, L.; Xu, B.; Zhang, Z.-M.; Zhang, J., Chin. J. Chem . 2024, 42, 2466-2470; (h) Dong, K.; Fang, C.; Li, Z.; Xu, B.; Zhang, Z.-M.; Zhang, J., Chin. J. Chem . 2025, 43, 2199-2205; (i) Li, S.; Chen, Q.; Zhang, Z.-M.; Zhang, J., Green Synth. Catal. 2021, 2, 374-376; (j) Li, W.; Zhang, J., Acc. Chem. Res. 2024, 57, 489-513.
[17] Yuan K.; Feoktistova T.; Cheong P. H.-Y.; Altman, R. A.,Chem. Sci. 2021, 12, 1363-1367.
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