一種合成3-氟喹啉衍生物的方法
【技術(shù)領(lǐng)域】
[0001] 本發(fā)明涉及含有氣原子的芳香雜環(huán)化合物，具體地說(shuō)是一種合成3-氣唾嘟衍生 物的方法。
【背景技術(shù)】
[0002] 含氣有機(jī)化合物由于其穩(wěn)定的碳-氣鍵，氣碳相特性，親脂性，偽擬效應(yīng)，代謝 穩(wěn)定性和氨鍵作用等特性，被廣泛應(yīng)用于醫(yī)藥、農(nóng)藥、材料等領(lǐng)域。尤其是在醫(yī)藥方面， W含氣芳香族化合物為活性基團(tuán)的一類藥物有著舉足輕重的作用。據(jù)報(bào)道，在所有商 品化的醫(yī)藥和農(nóng)藥中，含氣藥物所占比例高達(dá)20%左右。[文獻(xiàn)1 :a)H. Schofield, J. Fluorine Chem. 1999, 100, 7 ; b) H. J. Bohm, D. Banner, S. BendeIs, M. Kansy, B Kuhn, K. Muller,U.Obst-Sander,M. Stahl, ChemBioChem2004, 5, 637;c)K. Muller, C. Faeh, F. Diederich, Science2007, 317, 1881 ： d) W. K. Hagmann, J. Med. Chem. 2008, 51, 4359 ： e) D. O' Hagan, Chem. Soc. Rev. 2008, 37, 308：f)S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc.民ev. 2008, 37, 320. For the bookson fluorine in organic and medicinal chemistry:g)P. Kirsch. Modern Fluoroorganic Chemistry:Synthesis Reactivity Applications,Wiley-VCH,Weinheim, 2004：h)1.0 jima, Fluorine in Medicinal Chemistry and Chemical Biology, Wiley-Blackwell, Chi Chester,2009.] 如何在有機(jī)分子中引入氣原子一直是有機(jī)氣化學(xué)的研究重點(diǎn)，且已在過(guò)去的幾十年中取 得了長(zhǎng)足的發(fā)展。但是構(gòu)建芳基碳-氣鍵仍然極具挑戰(zhàn)性。[文獻(xiàn)2:a)TJuruya，C. A. Kuttruff, T. Ritter, Curr. Op in. Drug Disc. Dev. 2008, 11, 803：b)T. Furuya, A. S. Kamlet, T.民itter, Nature2011, 473, 470 : c) T. Liang, C. N. Neumann, T.民itter, Angew. Chem. 2013, 125, 8372 ;Angew. Chem. Int. Ed. 2013, 52, 8214.]。尤其對(duì)于具有潛在生物 學(xué)活性的芳香雜環(huán)類化合物，其氣化方法仍然局限于經(jīng)典氣化反應(yīng)如因交換反應(yīng)和 希曼反應(yīng)，其底物適用范圍相對(duì)較窄，已無(wú)法滿足現(xiàn)代醫(yī)藥材料界對(duì)含氣化合物的迫 切需求。[文獻(xiàn) 3:a)G.Balz，G.Schiemann，Ber.Dtsch.Oiem.Ges.l927,60，1186;b) G. C. Finger, C. W. Kruse, J. Am. Chem. Soc. 1956, 78, 6034; C) G. A. 01 ah, J. T. Welch, Y. D. Vankar, M. No jima, L. Kerekes, J. A. Olah, J. Org. Qiem. 1979, 44, 3872; d) D. J. Adams, J. 比Clark, Chem. Soc. Rev. 1999, 28, 225.]由過(guò)渡金屬催化的交叉偶聯(lián)反應(yīng)與直接碳 氨鍵官能化反應(yīng)，是目前報(bào)道最多的氣化反應(yīng)類型。[文獻(xiàn)4 :For recent reviews on the transition metal-catalyzedfluorination, see:a)V. V. Grushin, Acc. Chem. 民es.2010, 43, 160;b)T.Furuya,J.E.M.N.Klein, T. Ritter, Synthesis2010, 1804;c)A .Vigalok, 0rganometallics2011, 30, 4802;d)C. Hollingworth, V. Gouverneur, Chem. Commun. 2012, 48, 2929; e)G. Liu, Org. Biomol. Qiem. 2012, 10, 6243. For selected reviews and works on typical catalytic fluorination via C-H functionalization, see:a) K. M. Engle, T. -S. Mei, X. Wang, J. -Q. Yu, Angew. Chem. 2011，123, 1514; Angew. Chem. Int. Ed. 2011，50，1478 ; b) D. Leow, G. Li, T. -S. Mei, J. -Q. Yu, Nature2012, 486, 518 ; c) K. M. Engle, T. -S. Mei, M. Wasa, J. -Q. Yu, Acc. Chem. Res. 2012, 45, 788 ; d) K. L?加11，W. Q. Anani, M. S. Sanford, J. Am. Chem. Soc. 2006, 128, 7134; e) X. Wang, T. -S. Mei, J. -Q. Yu, J. Am. Chem. Soc. 2009，131，7520; f) K. S. L. Chan, M. Wasa, X. Wang, J. -Q. Yu, Angew. Chem. 2011，123, 9247; Angew. Chem. Int. Ed. 2011，50, 9081; g)B. Yao, Z. -L. Wang, H. 化ang, D. -X. Wang, L. Zhao, M. -X. Wang, J. Org. Qiem. 2012, 77, 3336; h) S. J. Lou, D. Q. Xu, A. B. Xia, X. F. Wang, Y. K. Liu, X. H Du, Z. Y. Xu, Chem. Commun. 2013, 49, 6218; i) T. Truong, K. Klimovica,0. Daugulis, J. Am. Chem. Soc. 2013, 135,9342.For selected works on transition metal-mediated or catalyzed C-F bond formation, see:a)T. Furuya,比 M. Kaiser, T. Ritter, Angew. Chem. 2008, 120, 6082; Angew. Qiem. Int. Ed. 2008, 47, 5993; b) T. Furuya, T. Ritter, Org. Lett. 2009, 11，2860; c) T. Furuya, A. E. Strom, T. Ritter, J. Am. Chem. Soc. 2009，131，1662 ; d) D. A. Watson, M. J. Su, G. Teverovskiy, Y. Zhang, J. Garcia-Fortanet，T.Kinzel，S. L. Buchwald, Science2009, 325, 166l:e)P. Tang, T. I^uruya，T. Ritter, J. Am. Qiem. Soc. 2010, 132, 12150 ;f)P. Tang, T. Ritter, Tetrahedron201 1，67, 4449; g) T. NoGl，T. J. Maimone, S. L. Buchwald, Angew. Qiem. 2011，123, 906