SIOC English
有机化学
高级检索

有机化学 >

0 202606029 - 202606029

DOI: https://doi.org/10.6023/cjoc202606029

综述与进展

有机三价碘不对称催化合成手性含氟化合物的研究进展

  • 钟晟昱 ,
  • 史雷
展开
  • a哈尔滨工业大学（深圳）理学院 深圳 518055

收稿日期: 2026-06-24

  修回日期: 2026-08-19

  网络出版日期: 2026-09-16

基金资助

国家自然科学基金(No. 22271069)、深圳市医学研究专项资金(No. D2501008)和深圳市科技计划资助(Nos. JCYJ20240813105110014 and GXWD20231130100539001)资助项目.

收起

Advances in Asymmetric Synthesis of Chiral Organofluorine Compounds via Hypervalent Iodine Catalysis

  • Zhong Shengyu ,
  • Shi Lei
Expand
  • aSchool of Science, Harbin Institute of Technology (Shenzhen), Shenzhen 518055

Received date: 2026-06-24

  Revised date: 2026-08-19

  Online published: 2026-09-16

Supported by

National Natural Science Foundation of China (No. 22271069), the Shenzhen Medical Research Fund (No. D2501008), and the Shenzhen Science and Technology Program (Nos. JCYJ20240813105110014 and GXWD20231130100539001).

Fold

摘要

含氟有机分子在药物和农药等领域有着广泛应用,但自然界中天然存在的有机氟化物极为稀少. 碳-氟键的构建本身也面临诸多挑战. 有机三价碘催化通过极性反转策略,将廉价亲核氟源转化为亲电性有机三价碘氟物种,为温和条件下不对称合成手性含氟化合物提供了独特路径. 本文系统梳理了2014年至今有机三价碘催化不对称合成手性含氟化合物的研究进展,以手性单氟化合物、双氟化合物和多氟化合物的合成为框架,依次讨论了羰基α-氟化、烯烃氟环化、苯酚去芳构化氟化、联烯氟化、1,2-二氟化、偕二氟化、1,3-二氟化以及基于含三氟甲基烯烃的氟化反应等转化类型,分析了代表性体系的催化剂设计、对映选择性控制因素和催化机制,总结了该领域在催化剂发展、氧化还原循环和机理认知等方面的现状与挑战,并对未来发展方向进行了展望.

关键词： 有机三价碘; 不对称催化; 亲核氟化; 手性含氟化合物; 极性反转

本文引用格式

钟晟昱 , 史雷 . 有机三价碘不对称催化合成手性含氟化合物的研究进展[J]. 有机化学, 0 : 202606029 -202606029 . DOI: 10.6023/cjoc202606029

Abstract

Organofluorine compounds are widely applied in pharmaceuticals and agrochemicals, yet naturally occurring organic fluorides are extremely rare. Notably, the construction of carbon-fluorine bonds poses considerable challenges. Hypervalent iodine(III) catalysis offers a distinct approach to the asymmetric synthesis of chiral organofluorine compounds under mild conditions by reversing the polarity of inexpensive nucleophilic fluoride sources to generate electrophilic hypervalent iodine(III) fluoride species. This Review systematically summarizes the progress in hypervalent iodine(III)-catalyzed asymmetric synthesis of chiral organofluorine compounds from 2014 to the present, covering the construction of chiral monofluorinated, difluorinated, and polyfluorinated molecules. Representative transformations discussed include carbonyl α-fluorination, olefin fluorocyclization, fluorinative dearomatization of phenols, fluorination of allenes, 1,2-difluorination, gem-difluorination, 1,3-difluorination, and fluorination of CF3-substituted alkenes. Key aspects of the reported systems, including catalyst design, enantioselectivity control and catalytic mechanisms, are discussed. Finally, current challenges and future directions are highlighted.

Key words： hypervalent iodine(III); asymmetric catalysis; nucleophilic fluorination; chiral organofluorine compounds; umpolung

参考文献

[1] (a) O′Hagan, D. Chem. Soc. Rev.2008, 37, 308.
(b) Liu Q.; Ni C.; Hu, J. Natl. Sci. Rev. 2017, 4, 303.
(c) Aufiero M.; Gilmour, R. Acc. Chem. Res. 2018, 51,1701.
(d) Meyer, S.; Häfliger, J.; Gilmour, R.Chem. Sci. 2021, 12, 10686.
(e) Poole, W. G.; Peron, F.; Fox, S. J.; Wells, N.; Skylaris, C.-K.; Essex, J. W.; Kuprov, I.; Linclau, B. J. Org. Chem. 2024, 89, 8789.
[2] (a) Müller K.; Faeh C.; Diederich F. Science2007, 317, 1881.
(b) Purser S.; Moore P. R.; Swallow S.; Gouverneur, V. Chem. Soc. Rev.2008, 37, 320.
(c) Gillis, E.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med. Chem. 2015, 58, 8315.
[3] (a) Wang J.; Sánchez-Roselló M.; Aceña J. L.; del Pozo C.; Sorochinsky A. E.; Fustero S.; Soloshonok V. A.; Liu H. Chem. Rev.2014, 114, 2432.
(b) Zhou Y.; Wang J.; Gu Z.; Wang S.; Zhu W.; Aceña J. L.; Soloshonok V. A.; Izawa K.; Liu H. Chem. Rev.2016, 116, 422.
(c) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822.
(d) Inoue, M.; Sumii, Y.; Shibata, N. ACS Omega 2020, 5, 10633.
(e) Grygorenko, O. O.; Melnykov, K. P.; Holovach, S.; Demchuk, O. ChemMedChem 2022, 17, e202200365.
(f) Du, Y.; Bian, Y.; Baecker, D.; Dhawan, G.; Semghouli, A.; Kiss, L.; Zhang, W.; Sorochinsky, A. E.; Soloshonok, V. A.; Han, J. Chem. Eur. J. 2025, 31, e202500662.
[4] (a) Fujiwara T.; O′Hagan, D. J. Fluorine Chem.2014, 167, 16.
(b) Ogawa Y., Tokunaga E., Kobayashi O., Hirai K., Shibata N. iScience2020, 23, 101467.
(c) Wang, Q., Song, H., and Wang, Q. Chin. Chem. Lett. 2022, 33, 626.
[5] (a) Preshlock S.; Tredwell M.; Gouverneur V. Chem. Rev.2016, 116, 719.
(b) Rong J.; Haider A.; Jeppesen T. E.; Josephson L.; Liang, S. H. Nat. Commun.2023, 14, 3257.
[6] (a) O′Hagan D.; Harper, D. B. J. Fluorine Chem.1999, 100, 127.
(b) Walker M. C.; Chang, M. C. Y. Chem. Soc. Rev.2014, 43, 6527.
(c) Reichel, M.; Karaghiosoff, K. Angew. Chem., Int. Ed. 2020, 59, 12268.
[7] O′Hagan D.; Deng H. Chem. Rev.2015, 115, 634.
[8] (a) Butler A.; Sandy M. Nature2009, 460, 848.
(b) Petkowski J. J.; Seager S.; Bains W. Sci. Rep.2024, 14, 15575.
[9] Wei L.; Huang C.; Luo Y.Sci. China: Life Sci. 2025, 55, 2124.
[10] (a) Lal G. S.; Pez G. P.; Syvret, R. G. Chem. Rev.1996, 96, 1737.
(b) Ma J.-A.; Cahard D. Chem. Rev.2004, 104, 6119.
(c) Brunet, V. A.; O′Hagan, D. Angew. Chem., Int. Ed. 2008, 47, 1179.
(d) Kirk, K. L. Org. Process Res. Dev. 2008, 12, 305.
(e) Zhu, Y.; Han, J.; Wang, J.; Shibata, N.; Sodeoka, M.; Soloshonok, V. A.; Coelho, J. A. S.; Toste, F. D. Chem. Rev. 2018, 118, 3887.
(f) Li, M.; Xue, X.-S.; Cheng, J.-P. Acc. Chem. Res. 2020, 53, 182.
(g) Kalita, S. J.; Qi, J.; Xiao, L.; Saha, D.; Huang, Y.-Y.; Shibata, N. Chem. Rev. 2025, 125, 8477.
[11] (a) Meyer D.; Jangra H.; Walther F.; Zipse H.; Renaud P. Nat. Commun.2018, 9, 4888.
(b) Bui T. T.; Hong W. P.; Kim, H.-K. J. Fluorine Chem.2021, 247, 109794.
(c) Zou, Z.; Zhang, W.; Wang, Y.; Pan, Y. Org. Chem. Front. 2021, 8, 2786.
(d) Wang, M.; Ruskin, J.; Marques, J.; Garrison, N.; Lectka, T. Chem. Rev. 2025, 125, 9382.
(e) Li, J.; Chiou, M.-F.; Bao, H. Org. Chem. Front. 2026, 13, 10.1039/D6QO00260A.
[12] (a) Champagne P. A.; Desroches J.; Hamel J.-D.; Vandamme M.; Paquin J.-F. Chem. Rev.2015, 115, 9073.
(b) Caron, S. Org. Process Res. Dev.2020, 24, 470.
(c) Leibler, I. N.-M.; Gandhi, S. S.; Tekle-Smith, M. A.; Doyle, A. G. J. Am. Chem. Soc. 2023, 145, 9928.
[13] (a) Li X.; Chen P.; Liu, G. Beilstein J. Org. Chem.2018, 14, 1813.
(b) Bauer A.; Maulide N. Chem. Sci.2021, 12, 853.
(c) Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2024, 124, 11108.
[14] Okuyama T.; Takino T.; Sueda T.; Ochiai, M. J. Am. Chem. Soc.1995, 117, 3360.
[15] Weinland R. F.; Stille, W. Ber. Dtsch. Chem. Ges.1901, 34, 2631.
[16] Stang P. J.; Zhdankin, V. V. Chem. Rev.1996, 96, 1123.
[17] (a) Zupan, M.; Pollak, A.J. Chem. Soc., Chem. Commun. 1975, 715.
(b) Hara S.; Nakahigashi J.; Ishi-I K.; Sawaguchi M.; Sakai H.; Fukuhara T.; Yoneda N. Synlett1998, 495.
(c) Sawaguchi, M.; Hara, S.; Yoneda, N.J. Fluor. Chem. 2000, 105, 313.
(d) Yoneda, N. J. Fluor. Chem. 2004, 125, 7.
[18] (a) Kitamura T.; Kuriki S.; Morshed M. H.; Hori Y. Org. Lett.2011, 13, 2392.
(b) Sarie J. C.; Thiehoff C.; Mudd R. J.; Daniliuc C. G.; Kehr G.; Gilmour, R. J. Org. Chem.2017, 82, 11792.
[19] Kong W.; Feige P.; de Haro T.; Nevado, C. Angew. Chem., Int. Ed.2013, 52, 2469.
[20] Roth H. G.; Romero N. A.; Nicewicz D. A. Synlett2016, 27, 714.
[21] (a) Dohi T.; Maruyama A.; Yoshimura M.; Morimoto K.; Tohma H.; Kita, Y. Angew. Chem., Int. Ed.2005, 44, 6193.
(b) Ochiai M.; Takeuchi Y.; Katayama T.; Sueda T.; Miyamoto, K. J. Am. Chem. Soc.2005, 127, 12244.
[22] (a) Cai Q.; Ma, H. Acta Chim. Sin.2019, 77, 213 (in Chinese)
(蔡倩, 马浩文, 化学学报, 2019, 77, 213).
(b) Parra, A. Chem. Rev. 2019, 119, 12033.
(c) Singh, F. V.; Shetgaonkar, S. E.; Krishnan, M.; Wirth, T. Chem. Soc. Rev. 2022, 51, 8102.
[23] Basdevant B.; Legault, C. Y. Org. Lett.2015, 17, 4918.
[24] Suzuki S.; Kamo T.; Fukushi K.; Hiramatsu T.; Tokunaga E.; Dohi T.; Kita Y.; Shibata N. Chem. Sci.2014, 5, 2754.
[25] Pluta R.; Krach P. E.; Cavallo L.; Falivene L.; Rueping M. ACS Catal.2018, 8, 2582.
[26] Wang Y.; Yuan H.; Lu H.; Zheng W.-H. Org. Lett.2018, 20, 2555.
[27] Zhou H.-J.; Yao Y.-P.; Zhang T.; Chen B.; Wu X.; Zhao H.; Zeng J.; Chen J.-A.; Xiao X.; Chen F.-E. Green Chem.2023, 25, 10447.
[28] Zhong S.; Yu Z.; Zhu Y.; Shi L. Org. Lett.2025, 27, 3452.
[29] (a) Scheidt F.; Neufeld J.; Schäfer M.; Thiehoff C.; Gilmour R. Org. Lett.2018, 20, 8073.
(b) Neufeld J.; Stünkel T.; Mück-Lichtenfeld C.; Daniliuc C. G.; Gilmour, R. Angew. Chem., Int. Ed.2021, 60, 13647.
(c) Wang, Q.; Biosca, M.; Himo, F.; Szabό, K. J. Angew. Chem., Int. Ed. 2021, 60, 26327.
(d) Longuet, M.; Vitse, K.; Martin-Mingot, A.; Michelet, B.; Guégan, F.; Thibaudeau, S. J. Am. Chem. Soc. 2024, 146, 12167.
(e) Sweeting, S. G.; Lennox, A. J. J. J. Am. Chem. Soc. 2025, 147, 19329.
[30] Woerly E. M.; Banik S. M.; Jacobsen, E. N. J. Am. Chem. Soc.2016, 138, 13858.
[31] Menie K. M.; Banik S. M.; Reichert E. C.; Jacobsen, E. N. J. Am. Chem. Soc.2018, 140, 4797.
[32] Sarie J.; Thiehoff C.; Neufeld J.; Daniliuc C. G.; Gilmour, R. Angew. Chem., Int. Ed.2020, 59, 15069.
[33] Häfliger J.; Sokolova O. O.; Lenz M.; Daniliuc C. G.; Gilmour, R. Angew. Chem., Int. Ed.2022, 61, e202205277.
[34] Wang Q.; Lübcke M.; Biosca M.; Hedberg M.; Eriksson L.; Himo F.; Szabό, K. J. J. Am. Chem. Soc.2020, 142, 20048.
[35] Zhu W.; Zhen X.; Wu J.; Cheng Y.; An J.; Ma X.; Liu J.; Qin Y.; Zhu H.; Xue J.; Jiang X. Nat. Commun.2021, 12, 3957.
[36] Chen J.; Li J.; Li X. Org. Lett.2025, 27, 13827.
[37] Stünkel T.; Siebold K.; Okumatsu D.; Murata K.; Ruyet L.; Daniliuc C. G.; Gilmour R. Chem. Sci.2023, 14, 13574.
[38] Wang Z.-X.; Xu Y.; Gilmour R. Nat. Commun.2024, 15, 5770.
[39] Banik S. M.; Medley J. W.; Jacobsen, E. N. J. Am. Chem. Soc.2016, 138, 5000.
[40] Molnár I. G.; Gilmour, R. J. Am. Chem. Soc.2016, 138, 5004.
[41] Scheidt F.; Schäfer M.; Sarie J. C.; Daniliuc C. G.; Molloy J. J.; Gilmour, R. Angew. Chem., Int. Ed.2018, 57, 16431.
[42] Haj M. K.; Banik S. M.; Jacobsen, E. N. Org. Lett.2019, 21, 4919.
[43] Banik S. M.; Medley J. W.; Jacobsen E. N. Science2016, 353, 51.
[44] Zhou B.; Haj M. K.; Jacobsen E. N.; Houk K. N.; Xue, X.-S. J. Am. Chem. Soc.2018, 140, 15206.
[45] Levin M. D.; Ovian J. M.; Read J. A.; Sigman M. S.; Jacobsen, E. N. J. Am. Chem. Soc.2020, 142, 14831.
[46] Häfliger J.; Livingstone K.; Daniliuc C. G.; Gilmour R. Chem. Sci.2021, 12, 6148.
[47] Tu F.-H.; Wang Y.; Li Z.; Yang S.; Li Y.; Tan D.-H.; Li Q.; Gao H.; Wang, H. Cell Rep. Phys. Sci.2022, 3, 101194.
[48] Ruyet L.; Roblick C.; Häfliger J.; Wang Z.-X.; Stoffels T. J.; Daniliuc C. G.; Gilmour, R. Angew. Chem., Int. Ed.2024, 63, e202403957.
[49] Banik S. M.; Mennie K. M.; Jacobsen, E. N. J. Am. Chem. Soc.2017, 139, 9152.
[50] Sharma H. A.; Mennie K. M.; Kwan E. E.; Jacobsen, E. N. J. Am. Chem. Soc.2020, 142, 16090.
[51] Zhong S.; Gan S.; Zhang X.; Song L.; Shi L. Adv. Sci.2025, 12, e06041.
[52] Kwon Y.-D.; Son J.; Chun J.-H. Org. Lett.2018, 20, 7902.
[53] Dean A. C.; Randle E. H.; Lacey A. J. D.; Giorio G. A. M.; Doobary S.; Cons B. D.; Lennox, A. J. J. Angew. Chem., Int. Ed.2024, 63, e202404666.
[54] Tu H.-F.; Lin S.; Tang Y.-J.; Liu L.-C.; Li Q.; Wang, H. Tetrahedron Chem.2023, 8, 100052.
[55] Meyer S.; Häfliger J.; Schäfer M.; Molloy J. J.; Daniliuc C. G.; Glimour, R. Angew. Chem., Int. Ed.2021, 60, 5430.
[56] Schäfer M.; Stünkel T.; Daniliuc C. G.; Gilmour, R. Angew. Chem., Int. Ed.2022, 61, e202205508.
[57] Yu Y.-J.; Häfliger J.; Wang Z.-X.; Daniliuc C. G.; Gilmour, R. Angew. Chem., Int. Ed.2023, 62, e202309789.
[58] (a) Winterson B.; Bhattacherjee D.; Wirth, T. Adv. Synth. Catal.2023, 365, 2676.
(b) Sokolovs, I.; Suna, E.; Francke, R.Acc. Chem. Res. 2026, 59, 1949.
[59] Wang Q.; Biosca M.; Himo F.; Szabό, K. J. Angew. Chem., Int. Ed.2021, 60, 26327.
[60] Lv W.-X.; Li Y.; Cai Y.-H.; Tan D.-H.; Li Z.; Li J.-L.; Li Q.; Wang H. Chem. Sci.,2022, 13, 2981.
[61] (a) Ning, Y.; Sivaguru, P.; Zanoni, G.; Anderson, E. A.; Bi, X.Chem 2020, 6, 486.
(b) Liu, X.-B.; Feng, S.-X.; Lin, S.; Qin, Q.-H.; Wang, H.*; Li, Q.CCS Chem. 2026, 8, 271.
[62] Li Y.; Liu X.-B.; Sham V.; Logvinenko I.; Xue J.-H.; Wu J.-Y.; Fu J.-L.; Lin S.; Liu Y.; Li Q.; Mykhailiuk P. K.; Wang, H. Angew. Chem., Int. Ed.2025, 64, e202422899.
Options
文章导航

/

〈 〉