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2018 , Vol. 38 >Issue 7: 1569 - 1585

DOI: https://doi.org/10.6023/cjoc201801041

综述与进展

二氟甲基化方法研究进展

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  • 西安近代化学研究所 氟氮化工资源高效开发与利用国家重点实验室 西安 710065

收稿日期: 2018-01-28

  修回日期: 2018-04-02

  网络出版日期: 2018-04-27

基金资助

陕西省重点研发计划（Nos.2017ZDXM-GY-042，2017ZDXM-GY-070）资助项目.

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Recent Progress on Difluoromethylation Methods

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  • State Key Laboratory of Fluorine & Nitrogen Chemicals, Xi'an Modern Chemistry Research Institute, Xi'an 710065

Received date: 2018-01-28

  Revised date: 2018-04-02

  Online published: 2018-04-27

Supported by

Project supported by the Key Research and Development Projects of Shanxi Province (Nos. 2017ZDXM-GY-042, 2017ZDXM-GY-070).

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摘要

二氟甲基官能团（CF2H）具有强的亲脂性和吸电子性，能显著增强有机分子的生理活性.含CF2H的分子在药物、农药等领域的应用研究已受到人们的极大关注.因此，如何简便、高效地向分子中引入CF2H基团成为当前有机氟化学领域的一个研究热点.近年来，新的二氟甲基化试剂及官能化方法得到了快速发展，为研究者提供了较为丰富的引入CF2H的手段.针对不同结构分子的二氟甲基化，对近年来发展的高效二氟甲基化试剂及二氟甲基化过程涉及的新反应、新催化剂及反应机理做着重介绍，最后将对二氟甲基化领域存在的问题和难点进行简要的展望.

关键词： 二氟甲基; 亲核试剂; 亲电试剂; 二氟卡宾; 直接二氟甲基化

本文引用格式

王为强, 余秦伟, 张前, 李江伟, 惠丰, 杨建明, 吕剑 . 二氟甲基化方法研究进展[J]. 有机化学, 2018 , 38(7) : 1569 -1585 . DOI: 10.6023/cjoc201801041

Abstract

The difluoromethyl functional group (CF2H) which has strong lipophilic and electron-withdrawing properties can significantly enhance the physiological activity of organic molecules. The applications of CF2H-containing compounds in the fields of drugs, agrochemicals and so on have attracted great attention of many research groups. Therefore, the development of effective and general methodologies for the selective incorporation of difluoromethyl groups has become one of the hotspots in the field of organic chemistry. Recently, new difluoromethylation reagents and methods that were able to efficiently incorporate the difluoromethyl group under mild conditions have been developed rapidly, that pave the way for the facile introduction of difluoromethyl group into site-specific positions of the target molecules. In this paper, we will first briefly introduce some organic molecules with different functional groups which can be difluoromethylated, and then focus on the development of the recent high-performance difluoromethylation reagents, new reactions and catalysts. Finally, we will discuss the remaining problems and challenges in this particular field.

Key words： drifluoromethyl; nucleophilic reagent; electrophilic reagent; difluorocarbene; direct difluoromethylation

参考文献

[1] (a) Vulpetti, A.; Dalvit, C. Drug Discovery Today 2012, 17, 890.
(b) Wang, J.; Sánchez-Roselló, M.; Acea, J. L.; Pozo, C. D.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev. 2014, 114, 2432.
[2] (a) Mìller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
(b) Ojima, I. Fluorine in Medicinal Chemistry and Chemical Biology, Wiley-Blackwell, Chichester (UK), 2009.
[3] (a) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475.
(b) Hollingworth, C.; Gouverneur, V. Chem. Commun. 2012, 48, 2929.
(c) Koike, T.; Akita, M. J. Fluorine Chem. 2014, 167, 30.
(d) Merino, E.; Nevado, C. Chem. Rev. Soc. 2014, 43, 6598.
(e) Ni, C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765.
[4] (a) Toulgoat, F.; Alazet, S.; Billard, T. Eur. J. Org. Chem. 2014, 2415.
(b) Barata-Vallejo, S.; Bonesi, S.; Postigo, A. Org. Biomol. Chem. 2016, 14, 7150.
(c) Shi, J.; Ren, G.; Wu, N.; Liu, X.; Xu, T.; Tan, C. Chin. J. Org. Chem. 2017, 37, 2131 (in Chinese).
(史建俊, 任贵华, 吴宁捷, 刘幸海, 许天明, 谭成侠, 有机化学, 2017, 37, 2131.)
(d) Hu, C.; Liu, J.; Du, X. Chin. J. Org. Chem. 2016, 36, 1051 (in Chinese).
(胡崇波, 刘建华, 杜晓华, 有机化学, 2016, 36, 1051.)
[5] (a) Kirsch, P. Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim (Germany), 2013.
(b) Besset, T.; Poisson, T.; Pannecoucke, X. Eur. J. Org. Chem. 2015, 2765.
[6] (a) Xiong, H.; Pannecoucke, X.; Besset, T. Chem. Eur. J. 2016, 22, 16734.
(b) Bos, M.; Poisson, T.; Pannecoucke, X.; Charette, A. B.; Jubault, P. Chem. Eur. J. 2017, 23, 4950.
(c) Pan, X.; Xia, H.; Wu, J. Org. Chem. Front. 2016, 3, 1163.
(d) Yerien, D. E.; Barata-Vallejo, S.; Postigo, A. Chem. Eur. J. 2017, 23, 14676.
(e) Zhang, X.; Cao, S. Tetrahedron Lett. 2017, 58, 375.
(f) Ni, C.; Zhu, L.; Hu, J. Acta Chim. Sinica 2015, 73, 90 (in Chinese).
(倪传法, 朱林桂, 胡金波, 化学学报, 2015, 73, 90.)
[7] (a) Manteau, B.; Pazenok, S.; Vors, J.-P.; Leroux, F. R. J. Fluorine Chem. 2010, 131, 140.
(b) Huang, C.-H.; Liang, T.; Harada, S.; Lee, E.; Ritter, T. J. Am. Chem. Soc. 2011, 133, 13308.
(c) Hojczyk, K. N.; Feng, P.; Zhan, C.; Ngai, M.-Y. Angew. Chem., Int. Ed. 2014, 53, 14559.
(d) Shen, X.; Zhou, M.; Ni, C.-F.; Zhang, W.; Hu, J.-B. Chem. Sci. 2014, 5, 117.
(e) Huang, R.; Huang, Y.; Lin, X.; Rong, M.; Weng, Z. Angew. Chem. 2015, 127, 5828.
(f) Liu, J.-B.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2015, 17, 5048.
(g) Feng, P.; Lee, K. N.; Lee, J. W.; Zhan, C.; Ngai, M.-Y. Chem. Sci. 2016, 7, 424.
[8] Chauret, N.; Guay, D.; Li, C.; Day, S.; Silva, J.; blouin, M.; Ducharme, Y.; Yergey, J. A.; Nicoli-Griffith, D. A. Bioorg. Med. Chem. Lett. 2002, 12, 2149.
[9] Mizukado, J.; Matsukawa, Y.; Quan, H.-D.; Tamura, M.; Sekiya, A. J. Fluorine Chem. 2006, 127, 400.
[10] Flynn, R. M.; Burton, D. J. J. Fluorine Chem. 2011, 132, 815.
[11] (a) Fedorov, O. V.; Struchkova, M. I.; Dilman, A. D. J. Org. Chem. 2016, 81, 9455.
(b) Song, X.; Tian, S.; Zhao, Z.; Zhu, D.; Wang, M. Org. Lett. 2016, 18, 3414.
[12] Mizukado, J.; Matsukawa, Y.; Quan, H.-D.; Tamura, M.; Sekiya, A. J. Fluorine Chem. 2005, 126, 365.
[13] Miethchen, R.; Hein, M.; Naumann, D.; Tyrra, W. Eur. J. Org. Chem. 1995, 1995, 1717.
[14] Levchenko, K.; Datsenko, O. P.; Serhiichuk, O.; Tolmachev, A.; Iaroshenko, V. O.; Mykhailiuk, P. K. J. Org. Chem. 2016, 81, 5803.
[15] Fier, P. S.; Hartwig, J. F. Angew. Chem. 2013, 125, 2146.
[16] Zhang, W.; Mao, W.; Wang, B.; Zeng, J.; Yang, J.; Lü, J. Sci. Sin. Chim. 2017, 47, 1312 (in Chinese).
(张伟, 毛伟, 王博, 曾纪珺, 杨建明, 吕剑, 中国科学:化学, 2017, 47, 1312.)
[17] (a) Piou, A.; Celerier, S.; Brunet, S. J. Fluorine Chem. 2012, 134, 103.
(b) Dolbier Jr., W. R.; Wang, F.; Tang, X.; Thomoson, C. S.; Wang, L. J. Fluorine Chem. 2014, 160, 72.
[18] (a) Prakash, G. K. S.; Zhang, Z.; Wang, F.; Ni, C.-F.; Olah, G. A. J. Fluorine Chem. 2011, 132, 792.
(b) Prakash, G. K. S.; Weber, C.; Chacko, S.; Olah, G. A. Org. Lett. 2007, 9, 1863.
[19] Zhu, J.; Liu, Y.; Shen, Q. Angew. Chem., Int. Ed. 2016, 55, 1.
[20] (a) Wang, F.; Zhang, W.; Zhu, J.; Li, H.; Huang, K.-W.; Hu, J. Chem. Commun. 2011, 47, 2411.
(b) Li, L.; Wang, F.; Ni, C.; Hu, J. Angew. Chem. 2013, 125, 12616.
(c) Ni, C.; Hu, J. Synthesis 2014, 46, 842.
[21] Xie, Q.; Ni, C.; Zhang, R.; Li, L.; Rong, J.; Hu, J. Angew. Chem., 2017, 129, 3254.
[22] (a) Erickson, J. A.; McLoughlin, J. I. J. Org. Chem. 1995, 60, 1626.
(b) Jeanmart, S.; F. Edmunds, A. J.; Lamberth, C.; Pouliot, M. Bioorg. Med. Chem. 2016, 24, 317.
[23] Thomoson, C. S.; Dolbier Jr., W. R. J. Org. Chem. 2013, 78, 8904.
[24] Mehta, V. P.; Greaney, M. F. Org. Lett. 2013, 15, 5036.
[25] Prakash, G. K. S.; Krishnamoorthy, S.; Kar, S.; Olah, G. A. J. Fluorine Chem. 2015, 180, 186.
[26] Ma, J.; Liu, Q.; Lu, G.; Yi, W. J. Fluorine Chem. 2017, 193, 113.
[27] Zhang, C. Adv. Synth. Catal. 2017, 359, 372.
[28] Heine, N. B., Studer, A. Org. Lett. 2017, 19, 4150.
[29] Yang, J., Jiang, M., Jin, Y., Yang, H., Fu, H. Org. Lett. 2017, 19, 2758
[30] (a) Medebielle, M.; Dolbier, W. R., Jr J. Fluorine Chem. 2008, 129, 930.
(b) Dilman, A. D.; Levin, V. V. Eur. J. Org. Chem. 2011, 2011, 831.
(c) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015, 115, 683.
(d) Alonso, C.; de Marigorta, E. M.; Rubiales, G.; Palacios, F. Chem. Rev. 2015, 115, 1847.
[31] Deng, Z.; Lin, J.-H.; Cai, J.; Xiao, J.-C. Org. Lett. 2016, 18, 3206.
[32] Krishnamoorthy, S., Prakash, G. K. S. Synthesis 2017, 49, 3394.
[33] Krishnamoorthy, S.; Kothandaraman, J.; Saldana, J.; Prakash, G. K. S. Eur. J. Org. Chem. 2016, 29, 4965.
[34] Hagiwara, T.; Fuchikami, T. Synlett 1995, 717.
[35] Zhao, Y.; Huang, W.; Zheng, J.; Hu, J. Org. Lett. 2011, 13, 5342.
[36] Chen, D.; Ni, C.; Zhao, Y.; Cai, X.; Li, X.; Xiao, P.; Hu, J. Angew. Chem., Int. Ed. 2016, 55, 12632.
[37] Trifonov, A. L.; Zemtsov, A. A.; Levin, V. V.; Struchkova, M. I.; Dilman, A. D. Org. Lett. 2016, 18, 3458.
[38] (a) Romanenko, V. D.; Kukhar, V. P. Chem. Rev. 2006, 106, 3868.
(b) Liang, T.; Neumann C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214.
[39] (a) Sato, K.; Omote, M.; Ando, A.; Kumadaki, I. J. Fluorine Chem. 2004, 125, 509.
(b) Murakami, S.; Ishii, H.; Tajima, T.; Fuchigami, T. Tetrahedron 2006, 62, 3761.
(c) Leung, L.; Linclau, B. J. Fluorine Chem. 2008, 129, 986.
(d) Nguyen, J. D.; Tucker, J. W.; Konieczynska, M. D.; Stephenson, C. R. J. J. Am. Chem. Soc. 2011, 133, 4160.
(e) Wallentin, C. J.; Nguyen, J. D.; Finkbeiner, P.; Stephenson, C. R. J. J. Am. Chem. Soc. 2012, 134, 8875.
(f) Belhomme, M.-C.; Poisson, T.; Pannecoucke, X. Org. Lett. 2013, 15, 3428.
[40] Yu, C.; Iqbal, N.; Park S.; Cho, E. J. Chem. Commun. 2014, 50, 12884.
[41] Arai, Y.; Tomita, R.; Ando, G.; Koike, T.; Akita, M. Chem. Eur. J. 2016, 22, 1262.
[42] Pannecoucke, X.; Poisson, T. Synlett 2016, 27, 2314.
[43] (a) Wang, X.; Zhao, S.; Liu, J.; Zhu, D.; Guo, M.; Tang, X.; Wang, G. Org. Lett. 2017, 19, 4187.
(b) Chen, H.; Wang, X.; Guo, M.; Zhao, W.; Tang, X.; Wang, G. Org. Chem. Front. 2017, 4, 2403.
[44] Banik, S. M.; Medley, J. W.; Jacobsen, E. N. Science 2016, 353, 51.
[45] (a) Gu, Y.; Leng, X.; Shen, Q. Nat. Commun. 2014, 5, 5405.
(b) Wu, J.; Liu, Y.; Lu, C.; Shen, Q. Chem. Sci. 2016, 7, 3757.
(c) Lu, C.; Gu, Y.; Wu, J.; Gu, Y.; Shen, Q. Chem. Sci. 2017, 8, 4848.
[46] Xu, L.; Vicic, D. A. J. Am. Chem. Soc. 2016, 138, 2536.
[47] Aikawa, K.; Serizawa, H.; Ishii, K.; Mikami, K. Org. Lett. 2016, 18, 3690
[48] Serizawa, H.; Ishii, K.; Aikawa, K.; Mikami, K. Org. Lett. 2016, 18, 3686.
[49] (a) Ge, S.; Chaladaj, W.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 4149.
(b) Rong, J.; Ni, C.; Hu, J. Asian J. Org. Chem. 2017, 6, 139.
[50] Bour, J. R.; Kariofillis, S. K.; Sanford, M. S. Organometallics 2017, 36, 1220.
[51] Miao, W.; Zhao, Y.; Ni, C.; Gao, B.; Zhang, W.; Hu, J. J. Am. Chem. Soc. 2018, 140, 880.
[52] Fujiwara, Y.; Dixon, J. A.; Rodriguez, R. A.; Baxter, R. D.; Dixon, D. D.; Collins, M. R.; Blackmond, D. G.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 1494.
[53] Tung, T. T.; Christensen, S. B.; Nielsen, J. Chem.-Eur. J. 2017, 23, 18125.
[54] (a) Ohtsuka, Y.; Yamakawa, T. Tetrahedron 2011, 67, 2323.
(b) Lin, Q.; Chu, L.; Qing, F.-L. Chin. J. Chem. 2013, 31, 885.
(c) Jung, J.; Kim, E.; You, Y.; Cho, E. J. Adv. Synth. Catal. 2014, 356, 2741.
[55] Li, J.; Wan, W.; Ma, G.; Chen, Y.; Hu, Q.; Kang, K.; Jiang, H.; Hao, J. Eur. J. Org. Chem. 2016, 4916.
[56] Huang, Z.; Matsubara, O.; Jia, S.; Tokunaga, E.; Shibata, N. Org. Lett. 2017, 19, 934.
[57] Ismalaj, E.; Glenadel, Q.; Billard, T. Eur. J. Org. Chem. 2017, 1911.
[58] Feng, Z.; Min, Q.; Zhang, X. Org. Lett. 2016, 18, 44.
[59] Deng, X. Y.; Lin, J. H.; Xiao, J. C. Org. Lett. 2016, 18, 4384.
[60] Feng, Z.; Min, Q.; Fu, X.; An, L.; Zhang, X. Nat. Chem. 2017, 9, 918.
[61] Fu, X. P.; Xiao, Y. L.; Zhang, X. Chin. J. Chem. 2018, 36, 143.
[62] Sheng, J.; Ni, H. Q.; Bian, K. J.; Li, Y.; Wang, Y. N.; Wang, X. S. Org. Chem. Front. 2018, 5, 606.
[63] (a) Lui, N.; Pazenok, S.; Shermolovich, Y. G. US 2011/0060167, 2011.
(b) Antons, S.; Lui, N.; Gerlach, A. US 2011/0082318, 2011.
(c) Thomas, R.; Ansgar, A.; Christian, M. WO 2016/023773, 2016.
(d) Norbert, M. T.; Norbert, L.; Stefan, M. US 20140243561, 2014.
[64] (a) Yun, J.; Yang, J. M.; Lu, J.; Zhang, Q.; Li, J. W.; Zhao, F. W.; Yu, Q. W.; Mei, S. N.; Wang, W. Q.; Li, Y. N.; Hui, F. CN 106831338, 2017.
(b) Yun, J.; Yang, J. M.; Lu, J.; Hui, F.; Li, Y. N.; Zhang, Q.; Li, J. W.; Zhao, F. W.; Yu, Q. W.; Wang, W. Q.; Mei, S. N. CN 106810421, 2017.
(c) Sun, D. A.; Li, C. Y.; Du, Y. M.; Zhang, W.; Zhang, J. W..; Ma, Y. B.; Zeng J. J.; Lu, J. J. Mol. Catal. 2013, 27, 242 (in Chinese). (孙道安, 李春迎, 杜咏梅, 张伟, 张建伟, 马洋博, 曾纪珺, 吕剑, 分子催化, 2013, 27, 242.)
[65] (a) Wang, Q.; Yu, X.; Jin, J.; Wu, Y.; Liang, Y. Chin. J. Chem. 2018, 36, 223.
(b) Zhou, N.; Xu, P.; Li, W.; Cheng, Y.; Zhu, C. Acta Chim. Sinica 2017, 75, 60 (in Chinese).
(周能能, 胥攀, 李伟鹏, 成义祥, 朱成建, 化学学报, 2017, 75, 60.)
[66] (a) Fujita, T.; Sanada, S.; Chiba, Y.; Sugiyama, K.; Ichikawa, J. Org. Lett. 2014, 16, 1398.
(b) Fujita, T.; Sugiyama, K.; Sanada, S.; Ichitsuka, T.; Ichikawa, J. Org. Lett. 2016, 18, 248.
[67] Mykhailiuk, P. K. Angew. Chem., Int. Ed. 2015, 54, 1.
[68] Li, J.; X.-L.; Yu, Cossy, J.; Lv, S.-Y.; Zhang, H.-L.; Su, F.; Mykhailiuk, P. K.; Wu, Y. Eur. J. Org. Chem. 2017, 2017, 266.
[69] Nawrot, E.; Jonczyk, A. J. Org. Chem. 2007, 72, 10258.
[70] Zafrani, Y.; Amir, D.; Yehezkel, L.; Madmon, M.; Saphier, S.; Karton-Lifshin, N.; Gershonov, E. J. Org. Chem. 2016, 81, 9180.

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