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DOI: https://doi.org/10.6023/cjoc202603001

综述与进展

光学纯α-羰基单氟代手性中心构建的研究进展

  • 金成 ,
  • 祝鑫 ,
  • 吴宪姚 ,
  • 巫辅龙 ,
  • 王长娟 ,
  • 廉翔 ,
  • 吴晶晶 ,
  • 吴范宏
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  • a上海应用技术大学化工与能源技术学部 上海 201418
    b上海绿色氟代制药工程技术研究中心 上海 201418
    c浙江海森药业股份有限公司 浙江东阳 322100

收稿日期: 2026-03-02

  修回日期: 2026-05-11

  网络出版日期: 2026-06-18

基金资助

国家自然科学基金(No.22403066,21672151,21602136)资助项目.

收起

Research Progress on the Construction of Optically Pure α-Keto Monofluoro Chiral Centers

  • Jin Cheng ,
  • Zhu Xin ,
  • Wu Xianyao ,
  • Wu Fulong ,
  • Wang Changjuan ,
  • Lian Xiang ,
  • Wu Jingjing ,
  • Wu Fanhong
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  • aFaculty of Chemical Engineering and Energy Technology, Shanghai Institute of Technology, Shanghai 201418
    bShanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai 201418
    cZhejiang Hissen Pharmaceutical Co., Ltd., Dongyang, Zhejiang 322100

Received date: 2026-03-02

  Revised date: 2026-05-11

  Online published: 2026-06-18

Supported by

National Natural Science Foundation of China (No. 22403066, 21672151 and 21602136).

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摘要

含氟有机化合物因其独特的物理化学性质,在制药、农用化学品及材料科学等领域具有广泛应用。其中,含有手性中心的光学纯α-羰基单氟代化合物因其在调控生物活性与分子构型中的关键作用,近年来在药物发现领域备受关注。本文系统总结了近十年来构建此类结构的主要策略,通过三个方向进行阐述：(1)通过C—F键生成实现不对称氟化;(2)利用含氟亲核/亲电砌块参与不对称C—C键构筑;(3)新兴的自由基与协同催化模式。通过深入探讨氟原子的电子效应、空间特性等对反应活性和立体选择性的影响,分析不同反应的底物适用范围与局限性,为未来单氟代手性中心的构建提供理性设计思路。

关键词： α-氟酮; 手性中心; 不对称氟化; 含氟砌块

本文引用格式

金成 , 祝鑫 , 吴宪姚 , 巫辅龙 , 王长娟 , 廉翔 , 吴晶晶 , 吴范宏 . 光学纯α-羰基单氟代手性中心构建的研究进展[J]. 有机化学, 0 : 3001 . DOI: 10.6023/cjoc202603001

Abstract

Fluorinated organic compounds, endowed with unique physicochemical properties, have found extensive applications in pivotal fields including pharmaceuticals, agrochemicals, and materials science. Notably, enantiomerically pure α-carbonyl monofluorinated compounds containing chiral centers have garnered considerable attention in drug discovery in recent years, owing to their crucial role in regulating biological activity and modulating molecular configuration. This review systematically summarizes the major synthetic strategies for constructing such structures over the past decade, which are categorized into three aspects: (1) Achievement of asymmetric fluorination through C—F bond formation; (2) Asymmetric formation of C—C bonds utilizing fluorinated nucleophilic or electrophilic building blocks; (3) Emerging radical and synergistic catalysis modes. By critically analyzing the electronic and steric effects of fluorine atoms on reaction activity and stereoselectivity, we assess the substrate scope and inherent limitations of existing methodologies, aiming to provide rational design principles for the future synthesis of monofluorinated chiral centers.

Key words： α-fluoroketone; chiral center; asymmetric fluorination; fluorine-containing building

参考文献

[1] Bertelli, C.; Gouverneur, V.Org. Biomol. Chem. 2006, 4, 2065.
[2] Cahard D.; Bizet, V. Chem. Soc. Rev.2014, 43, 135.
[3] Remete A. M.; Nonn M.; Escorihuela J.; Fustero S.; Kiss, L. Eur. J. Org. Chem.2021, 44, 5946.
[4] Wang Q.; Bian Y. P.; Gagan D.; Zhang W.; Smirnov A. E.; Ata M.; Soloshonok V. A.; Han, J. L. Chin. Chem. Lett.2024, 35, 138.
[5] Dobrowolski S.; Dürr M.; Gruber, M. Front. Oral Health.2022, 3, 873157.
[6] Han J. L.; Kiss L.; Ma H. B.; Remete A. M.; Sinkovic M. P.; Suresh D. M.; Riego R.; Santos F.; Mori H.; Soloshonok, V. A. Chem. Rev.2021, 121, 4678.
[7] Ghosh A.; Kallel M.; Ghosh S. K.; Saha, B. Res. Chem. Intermed.2013, 39, 2881.
[8] Munro D. D.; Wilson, L. Br. Med. J.1975, 3, 626.
[9] Youn K. S.; Seong W. C.; Won K. J.; Su H. J.; In D. J.; Yeong M. P.; Il W. C.; Jeong I. S.; Eun B. S.; Nari K.; Jin H.; Won, S. P. Life Sci.2011, 89, 331.
[10] Hartz B. P.; Brown W. D.; Ahring P. K.; Strøbæk D.; Mirza, N. R. J. Pharmacol. Exp. Ther.2005, 314, 282.
[11] Rodgers, W.; Ashley, D. F.; Scott, C.Antimicrob. Agents Chemother. 2013, 57, 1632.
[12] Ma J. A.; Cahard D.Chem. Rev.2004, 104, 6119.
[13] Lin J. H.; Xiao J. C.Tetrahedron Lett.2014, 55, 6147.
[14] Yang X.; Wu T.; Phipps R. J.; Toste, F. D. Chem. Rev.2015, 115, 826.
[15] Zhu Y.; Han J. L.; Wang J. D.; Shibata N.; Sodeoka M.; Soloshonok V. A.; Coelho J. A. S.; Toste, F. D. Chem. Rev.2018, 118, 3887.
[16] Butcher T. W.; Amberg W. M.; Hartwig, J. F. Angew. Chem. Int. Ed.2022, 134, e202112251.
[17] Wang X.; Hu, J. B. Phosphorus Sulfur Silicon Relat. Elem.2024, 199, 10.
[18] Liu S.; Zhou J.; Yu L.; Liu Y.; Huang Y.; Ouyang Y.; Liu G. K.; Xu X. H.; Shibata N. Chem. Rev.2025, 125, 4603.
[19] Kalita S. J.; Qi J.; Xiao L.; Saha D.; Huang Y. Y.; Shibata N. Chem. Rev.2025, 125, 8477.
[20] Fiorentino M. T.; Giammarco M.; Parrilli S.; Tossi A.; Bruni G.; Crisanti, M. Int. J. Antimicrob. Agents2001, 17, 151.
[21] Ito M.; Sato Y.; Shibata N. ACS Omega2020, 5, 10633.
[22] Fjelbye K.; Marigo M.; Clausen R. P.; Juhl K. Org. Lett.2016, 18, 1170.
[23] Bao X. Z.; Wei S. Q.; Zou, L. W., Song, Y. M.; Qu J. P.; Wang, B. M. Tetrahedron Asym.2016, 27, 436.
[24] González-Esguevillas, M.; Lorca, M.; Tortoreto, C.; Quintavalla, A.Chem. Eur. J. 2016, 3223.
[25] Zhang H. Y.; Cheng B.; Lu Z. Org. Lett.2018, 20, 4028.
[26] Peng S. Y.; Wang Z. F.; Zhang L. X.; Zhang X. H.; Huang Y. Nat. Commun.2018, 9, 375.
[27] Jiang, X. J.; Wang, H. T; He, H. Q.; Wang, W.; Wang, Y. Q.; Ke, Z. H.; Yeung, Y. Y.Adv. Synth. Catal. 2018, 360, 4710.
[28] Wang Y.; Yuan H.; Lu H. F.; Zheng, W. H. Org. Lett.2018, 20, 2555.
[29] Egami H.; Ryu T.; Nagato T.; Matsumoto K.; Yamamoto K.; Hirai, Y. Angew. Chem. Int. Ed.2020, 59, 14101.
[30] Ishihara K.; Nishimura K.; Yamakawa, K. Angew. Chem. Int. Ed.2020, 59, 17794.
[31] Grell Y.; Xie X. L.; Levlev S. I.; Meggers E. ACS Catal.2021, 11, 11396.
[32] Zhang Z. Y.; Ouyang Y. X.; Zhang T.; Yu, J. Q. J. Am. Chem. Soc.2025, 147, 7863.
[33] Wang, B. C.; Fan, S. X.; Zhang, C. S.; Sun, J. W.J. Am. Chem. Soc. 2025, 147, 10059.
[34] Liang Y. F.; Fu, G. C. J. Am. Chem. Soc.2014, 136, 5520.
[35] Ponra S.; Yang J. P.; Kerdphon,S.; Andersson, P. G. Angew. Chem. Int. Ed.2019, 58, 9282.
[36] Yang W. J.; Zhang J. H.; Li N.; Xie M. S.; Guo, H. M. Org. Chem. Front.2025, 12, 2746.
[37] Wang T. L.; Ding L. H.; Lu, Y. X. Chem. Commun.2015, 51, 10186.
[38] Carrillo E.; Švarm J.; Waldmann H. Org. Lett.2016, 18, 6014.
[39] Zhu Y.; Ni Y. F.; Vadim A. S.; Han J. L.; Pan Y. J. Fluor. Chem.2019, 219, 32.
[40] Dey A.; Jaiswal H.; Singh, V. K. Org. Lett.2021, 23, 9441.
[41] Biswas R. G.; Ray S. K.; Unhale R. A.; Singh, V. K. Org. Lett.2021, 23, 6504.
[42] Lu M. X.; Xiong Z. L.; Zhou Y.; Wang X.; Li X. Y.; Duan J. X.; Yao W. J.; Xia Y.; Wang Z. Chem. Commun.2021, 57, 4722.
[43] Kim S.; Jeong S.; Lee, S. Y. ACS Catal.2023, 13, 13838.
[44] Saini N.; Khajuria C.; Biswas R. G.; Singh, V. K. J. Org. Chem.2024, 89, 1264.
[45] Jin Y. H.; Wang X. P.; Ning L. W.; Wang R. J.; Li Y.; Zhang Y. C.; Chen, L. Y. J. Org. Chem.2024, 89, 8435.
[46] Trost B. M.; Saget T.; Lerchen A.; Huang, C. Angew. Chem. Int. Ed.2016, 55, 781.
[47] Carrillo, E.; El-Hage, O. D.; Švarm, J.; Ernst, M. O.; Waldmann, H. Angew. Chem. Int. Ed. 2016, 55, 13127.
[48] Li Y.; Li X.; Shang H. Q.; Chen X. Y.; Ren, X. F. J. Org. Chem.2016, 81, 9858.
[49] Venkataramasubramanian, V.; Mun, J. K.; Li, Y. D.; Yang, H. L.; Choong, E. S.Chem. Eur. J. 2017, 23, 1268.
[50] Balaji P. V.; Brewitz L.; Kumagai N.; Shibasaki, M. Angew. Chem. Int. Ed.2019, 58, 2644.
[51] Trost B. M.; Tracy J. S.; Yusoontorn, T. Angew. Chem. Int. Ed.2020, 59, 2370.
[52] Zhang X.; Wei Z. L.; Cao J. G.; Liang D. P.; Lin Y. J.; Duan H. F. Synlett2022, 33, 488.
[53] Zhao M. Y.; Zhao Z. Q.; Wei Z. L.; Cao J. G.; Liang D. P.; Lin Y. J.; Duan, H. F. J. Org. Chem.2024, 89, 4474.
[54] Jiao Z. W.; Bertrand J. B.; Jin Y. S.; Ge S. Z.; Sun J. R.; Hartwig, J. F. J. Am. Chem. Soc.2016, 138, 15980.
[55] Xie C.; Wu L. M.; Han L.; Soloshonok V. A.; Pan, Y. Angew. Chem. Int. Ed.2015, 54, 6019.
[56] Harrity J. K.; Mauduit M.; Brown A.; Noble, A. Angew. Chem. Int. Ed.2016, 55, 6767.
[57] Jin Y. S.; Chen M.; Ge S. Z.; Hartwig, J. F. Org. Lett.2017, 19, 1390.
[58] Zhang L. J.; Zhang W. Z.; Mei H. B.; Han J. L.; Soloshonok V. A.; Pan, Y. Org. Biomol. Chem.2017, 15, 311.
[59] Borra K.; Wolff, C. Angew. Chem. Int. Ed.2017, 56, 1390.
[60] Lu Y. H.; Gormley E. L.; Stoltz, B. M. Org. Lett.2018, 20, 5657.
[61] He Z. T.; Jiang X. Y.; Hartwig, J. F. J. Am. Chem. Soc.2019, 141, 13066.
[62] Yang S. Q.; Wang Y. F.; Zhao W. C.; Lin G. Q.; He, Z. T. J. Am. Chem. Soc.2021, 143, 7285.
[63] Kalita S. J.; Cheng F.; Fan Q. H.; Shibata N.; Huang, Y. Y. J. Org. Chem.2021, 86, 8695.
[64] Zheng, Y.; Zhang, S. H.; Low, K. H.; Zi, W. W.; Huang, Z. X.J. Am. Chem. Soc. 2022, 144, 1951.
[65] Lin, H. X.; Jiao, W.; Chen, Z. W.; Han, J.; Fang, D. M.; Wang, M.; Liao, J.Org. Lett. 2022, 24, 2197.
[66] Han J. X.; Hotchkin L.; Harrity, J. P. A. Chem. Eur. J.2022, 28, e202201595.
[67] Pérez E. L.; Barcons A.; Papadopoulos M.; Zakaryan A. Org. Lett.2023, 25, 6167.
[68] Liao Q. Y.; Ma C.; Wang Y. C.; Yang S. Q.; Ma J. S.; He, Z. T. Chin. Chem. Lett.2023, 34, 185.
[69] Lin H. X.; Huang X.; Jiao W.; Fang D. M.; Wang M.; Liao J. Org. Lett.2023, 25, 3239.
[70] Tian K.; Chang X.; Xiao L.; Dong X. Q.; Wang, C. J. Fundam. Res.2024, 4, 77.
[71] Gao F.; Wang X. J.; Li D.; Zhao S. N.; Wei X. P.; Li G. P.; He, Y. H. Zhao, X. J. Org. Lett.2025, 27, 9370.
[72] Hamada, S.; Sato, Y.; Komiya, Y.; Tanaka, K.Org. Lett. 2025, 27, 12172.
[73] Hou, M. M.; Lin, L.; Chai, X. P.; Zhao, X. W.; Qiao, B. K.; Jiang, Z. Y. Chem. Sci. 2019, 10, 6629.
[74] Muller M. L.; Kraus V.; Niggemann M.; Chen H. Y.; Lei A. W.; Bräse S.; Ciesielski, J. Chem. Eur. J.2020, 26, 13163.
[75] Mo X. L.; Huang H.; Zhang, G. Z. ACS Catal.2022, 12, 9944.
[76] Liu L.; Jiang Q.; Tang L.; Liu C.; Wang Y. Z.; Wu F. H.; Wu, J. J. Org. Lett.2024, 26, 10833.
[77] Wang, J. Y.; Yang, J.; He, J.; Lu, Z.J. Am. Chem. Soc. 2025, 147, 14065.
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