亲电二氟甲基试剂及其应用研究进展

doi:10.6023/cjoc202005016

摘要/Abstract

稳定、安全、便捷、高效的亲电二氟甲基化试剂的发展和应用是当前有机氟化学的热门研究领域.在过去的十几年里，由于新试剂和新方法的发展，亲电二氟甲基化反应取得了一定的进展.亲电二氟甲基试剂可以方便地向分子的富电子位点引入二氟甲基，同时还可以被还原作为二氟甲基自由基前体参与反应，因此在含氟化合物的合成上具有明显的优势.但是与亲核二氟甲基试剂及应用研究相比，仍然存在很大的发展空间.全面总结了过去十几年亲电型二氟甲基试剂的研究进展，从总体上介绍了亲电型二氟甲基试剂在氟化学中的应用和重要性，按试剂类型着重介绍和讨论了亲电型二氟甲基试剂的类型，参与的亲电二氟甲基化反应及其作为二氟甲基自由基前体的反应.

关键词: 亲电二氟甲基试剂, 亲电二氟甲基化反应, 自由基二氟甲基化反应, 二氟卡宾

In the past two decades, the development and application of bench-stable electrophilic difluoromethylating reagents have attracted considerable attention. Consequently, some progress in this area has been ongoing recently. Electrophilic difluoromethylating reagents play a very important role in the synthesis of fluorine-containing compounds, due to their capability of readily transferring difluoromethyl moiety (CF₂H) into wide range of nucleophiles, as well as being used as difluoromethyl radical(•CF₂H) precursorfor radical difluoromethylations. However, the electrophilic difluoromethylating reagents and application therein remain still underdeveloped in comparison with nucleophilic ones. The research advance in electrophilic difluoromethylating reagents in past two decades is reviewed.

Key words: electrophilic difluoromethylating reagent, electrophilic difluoromethylation reaction, radical difluoromethylation reaction, difluorocarbene

引用此文

秦文兵, 陈嘉怡, 熊威, 刘国凯. 亲电二氟甲基试剂及其应用研究进展[J]. 有机化学, 2020, 40(10): 3177-3195.

Qin Wenbing, Chen Jiayi, Xiong Wei, Liu Guokai. Recent Advance in Development and Application of Electrophilic Difluoromethylating Reagents[J]. Chinese Journal of Organic Chemistry, 2020, 40(10): 3177-3195.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

参考文献

[1] (a) Smart, B. E. Chem. Rev. 1996, 96, 1555.
(b) Jeschke, P.; Baston, E.; Leroux, F. R. Mini-Rev. Med. Chem. 2007, 7, 1027 and references therein.
(c) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.
(d) 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.
(e) Bassetto, M.; Ferla, S.; Pertusati, F. Future Med. Chem. 2015, 7, 527.
[2] (a) Goure, W. F.; Leschinsky, K. L.; Wratten, S. J.; Chupp, J. P. J. Agric. Food Chem. 1991, 39, 981.
(b) Pérez, R. A.; Sánchez-Brunete, C.; Miguel, E.; Tadeo, J. L. J. Agric. Food Chem. 1998, 46, 1864.
(c) Kirsch, P. Modern Fluoroorganic Chemistry:Synthesis, Reactivity, Applications, 2nd ed., Wiley-VCH, Weinheim, 2013.
[3] (a) Kirsch, P.; Bremer, B. Angew. Chem., Int. Ed. 2000, 39, 4216.
(b) Tasaka, T.; Takenaka, S.; Kabu, K.; Morita, Y.; Okamoto, H. Ferroelectronics 2002, 276, 83.
(c) Boltalina, O. V.; Nakajima, T. New Fluorinated Carbons:Fundamentals and Applications, Elsevier, Amsterdam, 2016.
[4] (a) Bégué, J. P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Fluorine, Wiley-VCH, Weinheim, 2008.
(b) Ojima, I. Fluorine in Medicinal Chemistry and Chemical Biology, Wiley-Blackwell, Chichester, 2009.
(c) Gouverneur, V.; Muller, K. Fluorine in Pharmaceutical and Medicinal Chemistry: From Biophysical Aspects to Clinical Applications, Imperial College Press, London, 2012.
[5] (a) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
(b) Purse, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
(c) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359.
(d) Kirk, K. L. Org. Process Res. Dev. 2008, 12, 305.
(e) Prakash, G. K. S.; Wang, F. Chim. Oggi 2012, 30, 30.
(f) Wang, J.; Liu, H. Chin. J. Org. Chem. 2011, 31, 1785(in Chinese). (王江, 柳红, 有机化学, 2011, 31, 1785.)
[6] For selected reviews on perfluoroalkylation reactions, see:(a) Lundgren, R. J.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 9322.
(b) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475.
(c) Wu, X.-F.; Neumann, H.; Beller, M. Chem.-Asian J. 2012, 7, 1744.
(d) Besset, T.; Schneider, C.; Cahard, D. Angew. Chem., Int. Ed. 2012, 51, 5048.
(e) Ye, Y.; Sanford, M. S. Synlett 2012, 2005.
(f) Qing, F.-L. Chin. J. Org. Chem. 2012, 32, 815(in Chinese). (卿凤翎, 有机化学, 2012, 32, 815.)
(g) Pan, F.; Shi, Z. Acta Chim. Sinica, 2012, 70, 1679(in Chinese). (潘菲, 施章杰, 化学学报, 2012, 70, 1679.)
(h) Wang, X.; Zhang, Y.; Wang, J. Sci. Sin. Chim. 2012, 42, 1417. (王兮, 张艳, 王剑波, 中国科学:化学, 2012, 42, 1417.)
(i) Chen, P.; Liu, G. Synthesis 2013, 45, 2929.
(j) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214.
(k) Xu, J.; Liu, X.; Fu, Y. Tetrahedron Lett. 2014, 55, 585.
(l) Wang, G.; He, X.; Dai, J.; Xu, H. Chin. J. Org. Chem. 2014, 34, 837(in Chinese). (王光祖, 赫侠平, 戴建军, 许华建, 有机化学, 2014, 34, 837.)
(m) Zhang, J.; Jin, C.; Zhang, Y. Chin. J. Org. Chem. 2014, 34, 662(in Chinese). (张霁, 金传飞, 张英俊, 有机化学, 2014, 34, 662.)
(n) Merino, E.; Nevado, C. Chem. Soc. Rev. 2014, 43, 6598.
(o) Chu, L.; Qing, F.-L. Acc. Chem. Res. 2014, 47, 1513.
[7] (a) Prakash, G. K. S.; Mandal, M.; Schweizer, S.; Petasis, N. A.; Olah, G. A. J. Org. Chem. 2002, 67, 3718.
(b) Narjes, F.; Koehler, K. F.; Koch, U.; Gerlach, B.; Colarusso, S.; Steinkhler, C.; Brunetti, M.; Altamura, S.; De Francesco, R.; Matassa, V. G. Bioorg. Med. Chem. Lett. 2002, 12, 701.
(c) Hu, J.; Zhang, W.; Wang. F. Chem. Commun. 2009, 7465.
[8] (a) Li, Y.; Hu, J. Angew. Chem., Int. Ed. 2005, 44, 5882.
(b) Prakash, G. K. S.; Weber, C.; Chacko, S.; Olah, G. A. Org. Lett. 2007, 9, 1863.
[9] (a) Cazzola, M.; Picciolo, S.; Matera, M. G. Expert Opin. Pharmacother. 2010, 11, 441.
(b) Kohl, B.; Sturm, E.; Rainer, G. US 4758579A, 1985.
(c) Gajjar, D. A.; Bello, A.; Ge, Z.; Christopher, L.; Grasela, D. M. Antimicrob. Agents Chemother. 2003, 47, 2256.
(d) Kastron, V. V.; Vitolin, R. O.; Fialkov, J. A.; Shelyazhenko, S. V. US 4219653, 1980.
[10] (a) Brahms, D. L. S.; Dailey, W. P. Chem. Rev. 1996, 96, 1585.
(b) Dolbier, W. R. Jr.; Battiste, M. A. Chem. Rev. 2003, 103, 1071.
(c) Fedoryński, M. Chem. Rev. 2003, 103, 1099.
(d) Romanenko, V. D.; Kukhar, V. P. Chem. Rev. 2006, 106, 3868.
(e) Prakash, G. K. S.; Hu, J. Acc. Chem. Res. 2007, 40, 921.
(f) Hu, J.; Zhang, W.; Wang, F. Chem. Commun. 2009, 7465.
(g) Zhang, C.-P.; Chen, Q.-Y.; Guo, Y.; Xiao, J.-C.; Gu, Y.-C. Chem. Soc. Rev. 2012, 41, 4536.
(h) Bizet, V.; Kowalczyk, R.; Bolm, C. Chem. Soc. Rev. 2014, 43, 2426.
(i) Ni, C.; Hu, J. Synthesis 2014, 46, 0842.
(j) Shen, X.; Hu, J. Eur. J. Org. Chem. 2014, 4437.
(k) Belhomme, M.-C.; Besset, T.; Poisson, T.; Pannecoucke, X. Chem.-Eur. J. 2015, 21, 12836.
(l) Barata-Vallejo, S.; Bonesi, S. M.; Postigo, A. Org. Biomol. Chem. 2015, 13, 11153.
(m) Ni, C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765.
(n) 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.)
(o) Pan, X.; Xia, H.; Wu, J. Org. Chem. Front. 2016, 3, 1163.
(p) Koike, T.; Akita, M. Chem 2018, 4, 409.
(q) Yerien, D. E.; Barata-Vallejo, S.; Postigo, A. Chem.-Eur. J. 2017, 23, 14676.
(r) Rong, J.; Ni, C.; Hu, J. Asian J. Org. Chem. 2017, 6, 139.
(s) Dilman, A. D.; Levin, V. V. Acc. Chem. Res. 2018, 51, 1272.
(t) Lemos, A.; Lemaire, C.; Luxen, A. Adv. Synth. Catal. 2019, 361, 1500.
(u) Koike, T.; Akita, M. Org. Biomol. Chem. 2019, 17, 5413.
(v) Wang, X.; Wang, X.; Wang, J. Tetrahedron 2019, 75, 949.
(w) Xie, Q.; Hu, J. Chin. J. Chem. 2020, 38, 202.
[11] Umemoto, T. Chem. Rev. 1996, 96, 1757.
[12] (a) Yagupol'skii, L. M.; Kondratenko, N. Y.; Timofeeva, G. N. Zh. Org. Khim. 1984, 20, 115.
(b) Umemoto, T.; Ishihara, S. J. Am. Chem. Soc. 1993, 115, 2156.
(c) Umemoto, T.; Ishihara, S.; Adachi, K. J. Fluorine Chem. 1995, 74, 77.
(d) Umemoto, T.; Ishihara, S. J. Fluorine Chem. 1999, 98, 75.
(e) Umemoto, T.; Adachi, K. J. Org. Chem. 1994, 59, 5692.
(f) Yang, J. J.; Kirchmeier, R. L.; Shreeve, J. M. J. Org. Chem. 1998, 63, 2656.
(g) Ma, J.-A.; Cahard, D. J. Org. Chem. 2003, 68, 8726.
[13] (a) Prakash, G. K. S.; Weber, C.; Chacko, S.; Olah, G. A. Org. Lett. 2007, 9, 1863.
(b) Prakash, G. K. S.; Weber, C.; Chacko, S.; Olah, G. A. J. Comb. Chem. 2007, 9, 920.
[14] Yue, C.-B.; Lin, J.-H.; Cai, J.; Zhang, C.-P.; Zhao, G.; Xiao, J.-C.; Li, H. RSC Adv. 2016, 6, 35705.
[15] (a) Noto, N.; Koike, T.; Akita, M. Chem. Sci. 2017, 8, 6375.
(b) Noto, N.; Tanaka, Y.; Koike, T.; Akita, M. ACS Catal. 2018, 8, 9408.
[16] (a) Tang, X.-J.; Thomoson, C. S.; Dolbier, W. R. Jr. Org. Lett. 2014, 16, 4594.
(b) Zhang, Z.; Tang, X.-J.; Thomoson, C. S.; Dolbier, W. R. Jr. Org. Lett. 2015, 17, 3528.
(c) Zhang, Z.; Tang, X.-J.; Dolbier, W. R. Jr. Org. Lett. 2015, 17, 4401.
(d) Rong, J.; Deng, L.; Tan, P.; Ni, C.; Gu, Y.; Hu, J. Angew. Chem., Int. Ed. 2016, 55, 2743.
(e) Fu, W.; Han, X.; Zhu, M.; Xu, C.; Wang, Z.; Ji, B.; Hao, X.-Q.; Song, M.-P. Chem. Commun. 2016, 52, 13413.
(f) Zhang, Z.; Tang, X.-J.; Dolbier, W. R. Jr. Org. Lett. 2016, 18, 1048.
(g) Miao, W.; Zhao, Y.; Ni, C.; Gao, B.; Zhang, W.; Hu, J. J. Am. Chem. Soc. 2018, 140, 880.
(h) Zhang, Z.; Martinez, H.; Dolbier, W. R. J. Org. Chem. 2017, 82, 2589.
(i) Zhu, M.; Fu, W.; Wang, Z.; Xu, C.; Ji, B. Org. Biomol. Chem. 2017, 15, 9057.
(j) Duchemin, N.; Buccafusca, R.; Daumas, M.; Ferey, V.; Arseniyadis, S. Org. Lett. 2019, 21, 8205.
(k) Wang, Z.-S.; Chen, Y.-B.; Zhang, H.-W.; Sun, Z.; Zhu, C.; Ye, L. J. Am. Chem. Soc. 2020, 142, 3636.
[17] (a) Lu, S.-L.; Li, X.; Qin, W.-B.; Liu, J.-J.; Huang, Y.-Y.; Wong, H. N. C.; Liu, G.-K. Org. Lett. 2018, 20, 6925.
(b) Liu, G.-K.; Li, X.; Qin, W.-B.; Peng, X.-S.; Wong, H. N. C.; Zhang, L.; Zhang, X. Chem. Commun. 2019, 55, 7446.
(c) Liu, G.-K.; Qin, W.-B.; Li, X.; Lin, L.-T.; Wong, H. N. C. J. Org. Chem. 2019, 84, 15948.
(d) Liu, G.-K.; Li, X.; Qin, W.-B.; Lin, W.-F.; Lin, L.-T.; Chen, J.-Y.; Liu, J.-J. Chin. Chem. Lett. 2019, 30, 1515.
[18] (a) Zhang, C.; Cao, H.; Wang, Z.; Zhang, C.; Chen, Q.; Xiao, J. Synlett 2010, 1089.
(b) Liu, G.; Mori, S.; Wang, X.; Noritake, S.; Tokunaga, E.; Shibata, N. New J. Chem. 2012, 36, 1769.
(c) Liu, G.; Wang, X.; Lu, X.; Xu, X.-H.; Tokunaga, E.; Shibata, N. ChemistryOpen 2012, 1, 227.
(d) Liu, G.; Wang, X.; Xu, X.-H.; Lu, X.; Tokunaga, E.; Tsuzuki, S.; Shibata, N. Org. Lett. 2013, 15, 1044.
[19] (a) Zhang, W.; Wang, F.; Hu, J. Org. Lett. 2009, 11, 2109.
(b) Pégot, B.; Urban, C.; Bourne, A.; Le, T. N.; Bouvet, S.; Marrot, J.; Diter, P.; Magnier, E. Eur. J. Org. Chem. 2015, 3069.
[20] (a) Prakash, G. K. S.; Zhang, Z.; Wang, F.; Ni, C.; Olah, G. A. J. Fluorine Chem. 2011, 132, 792.
(b) Yang, Y.; Lu, X.; Liu, G.; Tokunaga, E.; Tsuzuki, S.; Shibata, N. ChemistryOpen 2012, 1, 221.
[21] (a) Arai, Y.; Tomita, R.; Ando, G.; Koike, T.; Akita, M. Chem.-Eur. J. 2016, 22, 1262.
(b) Noto, N.; Koike, T.; Akita, M. J. Org. Chem. 2016, 81, 7064.
(c) Nakayama, Y.; Ando, G.; Abe, M.; Koike, T.; Akita, M. ACS Catal. 2019, 9, 6555.
[22] (a) Zhu, J.; Liu, Y.; Shen, Q. Angew. Chem., Int. Ed. 2016, 55, 9050.
(b) Zhu, J.; Zheng, H.; Xue, X.-S.; Xiao, Y.; Liu, Y.; Shen, Q. Chin. J. Chem. 2018, 36, 1069.
[23] Zheng, J.; Cai, J.; Lin, J.-H.; Guo, Y.; Xiao, J.-C. Chem. Commun. 2013, 49, 7513.
[24] (a) Zheng, J.; Lin, J.-H.; Cai, J.; Xiao, J.-C. Chem.-Eur. J. 2013, 19, 15261.
(b) Deng, X.-Y.; Lin, J.-H.; Zheng, J.; Xiao, J.-C. Chem. Commun. 2015, 51, 8805.
(c) Liu, C.; Deng, X.-Y.; Zeng, X.-L.; Zhao, G.; Lin, J.-H.; Wang, H.; Xiao, J.-C. J. Fluorine Chem. 2016, 192, 27.
[25] Hua, M.-Q.; Wang, W.; Liu, W.-H.; Wang, T.; Zhang, Q.; Huang, Y.; Zhu, W.-H. J. Fluorine Chem. 2016, 181, 22.
[26] Zheng, Q.-T.; Wei, Y.; Zheng, J.; Duan, Y.-Y.; Zhao, G.; Wang, Z.-B.; Lin, J.-H.; Zheng, X.; Xiao, J.-C. RSC Adv. 2016, 6, 82298.
[27] Deng, X.-Y.; Lin, J.-H.; Xiao, J.-C. J. Fluorine Chem. 2015, 179, 116.
[28] Zheng, J.; Lin, J.-H.; Yu, L.-Y.; Wei, Y.; Zheng, X.; Xiao, J.-C. Org. Lett. 2015, 17, 6150.
[29] (a) Reger, D. L.; Dukes, M. D. J. Organomet. Chem. 1978, 153, 67.
(b) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746.
[30] Feng, Z.; Min, Q.-Q.; Zhang, X. Org. Lett. 2016, 18, 44.
[31] Deng, X.-Y.; Lin, J.-H.; Xiao, J.-C. Org. Lett. 2016, 18, 4384.
[32] Fu, X.-P.; Xue, X.-S.; Zhang, X.-Y.; Xiao, Y.-L.; Zhang, S.; Guo, Y.-L.; Leng, X.; Houk, K. N.; Zhang, X. Nat. Chem. 2019, 11, 948.
[33] (a) Zheng, J.; Lin, J.-H.; Deng, X.-Y.; Xiao, J.-C. Org. Lett. 2015, 17, 532.
(b) Wei, Y.; Yu, L.; Lin, J.; Zheng, X.; Xiao, J. Chin. J. Chem. 2016, 34, 481.
[34] (a) Zheng, J.; Wang, L.; Lin, J.-H.; Xiao, J.-C.; Liang, S. H. Angew. Chem., Int. Ed. 2015, 54, 13236.
(b) Zheng, J.; Cheng, R.; Lin, J.-H.; Yu, D.-H.; Ma, L.; Jia, L.; Zhang, L.; Wang, L.; Xiao, J.-C.; Liang, S. H. Angew. Chem., Int. Ed. 2017, 56, 3196.
(c) Yu, J.; Lin, J.-H.; Xiao, J.-C. Angew. Chem., Int. Ed. 2017, 56, 16669.
(d) Luo, J.-J.; Zhang, M.; Lin, J.-H.; Xiao, J.-C. J. Org. Chem. 2017, 82, 11206.
(e) Chen, X.-L.; Zhou, S.-H.; Lin, J.-H.; Deng, Q.-H.; Xiao, J.-C. Chem. Commun. 2019, 55, 1410.
[35] (a) Lin, Q.-Y.; Xu, X.-H.; Zhang, K.; Qing, F.-L. Angew. Chem., Int. Ed. 2016, 55, 1479.
(b) Ran, Y.; Lin, Q.-Y.; Xu, X.-H.; Qing, F.-L. J. Org. Chem. 2016, 81, 7001.
(c) Lin, Q.-Y.; Ran, Y.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2016, 18, 2419.
(d) Hu, W.-Q.; Xu, X.-H.; Qing, F.-L. J. Fluorine Chem. 2018, 208, 73.
[36] Ran, Y.; Lin, Q.-Y.; Xu, X.-H.; Qing, F.-L. J. Org. Chem. 2017, 82, 7373.
[37] Yu, J.; Lin, J.-H.; Cao, Y.-C.; Xiao, J.-C. Org. Chem. Front. 2019, 6, 3580.
[38] Zhang, M.; Lin, J.-H.; Xiao, J.-C. Angew. Chem., Int. Ed. 2019, 58, 6079.
[39] (a) Urban, C.; Macé, Y.; Cadoret, F.; Blazejewski, J. C.; Magnier, E. Adv. Synth. Catal. 2010, 352, 2805.
(b) Urban, C.; Cadoret, F.; Blazejewski, J. C.; Magnier, E. Eur. J. Org. Chem. 2011, 4862.
(c) Macé, Y.; Magnier, E. Eur. J. Org. Chem. 2012, 2479.
[40] (a) Zhang, W.; Zhu, J.; Hu, J. Tetrahedron Lett. 2008, 49, 5006.
(b) He, Z.; Luo, T.; Hu, M.; Cao, Y.; Hu, J. Angew. Chem., Int. Ed. 2012, 51, 3944.
(c) He, Z.; Hu, M.; Luo, T.; Li, L.; Hu, J. Angew. Chem., Int. Ed. 2012, 51, 11545.
[41] Wang, X.; Liu, G.; Xu, X.-H.; Shibata, N.; Tokunaga, E.; Shibata, N. Angew. Chem., Int. Ed. 2014, 53, 1827.