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化学进展 2014, Vol. 26 Issue (04): 592-608 DOI: 10.7536/PC130904 前一篇   后一篇

• 综述与评论 •

基于C—H键官能团化的药物合成

龚浩, 杨义文, 匡春香*   

  1. 同济大学化学系 上海 200092
  • 收稿日期:2013-09-01 修回日期:2013-11-01 出版日期:2014-04-15 发布日期:2014-01-20
  • 通讯作者: 匡春香,e-mail:kuangcx@tongji.edu.cn E-mail:kuangcx@tongji.edu.cn
  • 基金资助:

    国家自然科学基金项目(No. 21272174)资助

Drug Synthesis via C—H Bond Functionalization

Gong Hao, Yang Yiwen, Kuang Chunxiang*   

  1. Department of Chemistry, Tongji University, Shanghai 200092, China
  • Received:2013-09-01 Revised:2013-11-01 Online:2014-04-15 Published:2014-01-20
  • Supported by:

    The work was supported by the National Natural Science Foundation of China (No.21272174)

过渡金属催化的C—H键官能团化是有机化学的重要研究内容,并被作为工具广泛应用于药物合成领域。本文阐述了C—H键官能团化的经典反应类型,着重综述了C—H键的芳基化、烯基化、烷基化、卤化、羟基化、胺化和C—H插入反应在药物合成中的应用,详细描述了具体药物的合成实例,并对重要的反应机理进行了分析,最后展望了C—H键官能团化在药物合成中的发展前景。

The C—H bond functionalization by transition metal is one of the essential contents in organic chemistry. And it has become an enabling tool in the synthesis of drugs. This review describes the classical reactions of C—H bond functionalization and focus on arylation, alkenylation, alkylation, halogenation, hydroxylation, amination, and insertion which provide a simple and rapid way for the drug synthesis. The detail of the applications and relevant mechanisms are also described. Finally we look forward to its development prospects in this field.

Contents
1 Introduction
2 C—C bond formation
2.1 sp2 C—H functionalization assisted by the directing group
2.2 sp2 C—H functionalization without the directing group
2.3 sp3 C—H functionalization assisted by the directing group
2.4 sp3 C—H functionalization without the directing group
3 C—H insertion
4 C—X bond formation
4.1 C—X bond formation assisted by the directing group
4.2 C—X bond formation without the directing group
5 Conclusion and outlook

中图分类号: 

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[1] Van H R, Verberg G. Trav. Chim. Pays-Bas, 1965, 84: 1263.
[2] Fujiwara Y, Moritani I, Danno S. J. Am. Chem. Soc., 1969, 91: 7166.
[3] Gol’dshleger N F, Tyabin M B, Shilov A E. Zh. Fiz. Khim., 1969, 43: 2174.
[4] 郭兴伟(Guo X W), 李志平(Li Z P), 李朝军(Li C J). 化学进展(Prog. Chem. ), 2010, 22(7): 1434.
[5] Quirk J, Thornton M, Kirkpatrick P. Nature, 2003, 2: 769.
[6] Taber D F, Neubert T D, Rheingold A L. J. Am. Chem. Soc., 2002, 124: 12416.
[7] 刘伟(Liu W. ), 毕艳兰(Bi Y L), 有机化学(Chin. J. Org. Chem. ), 2012, 32: 1041.
[8] Ouellet S G, Roy A, Molinaro C, Angelaud R, Marcoux J F, O’Shea P D, Davies I W. J. Org. Chem., 2011, 76: 1436.
[9] Seki M, Nagahama M. J. Org. Chem., 2011, 76: 10198.
[10] Wang G W, Yuan T T, Li D D. Angew. Chem. Int. Ed., 2011, 50: 1380.
[11] Blanchot M, Candito D A, Larnaud F, Lautens M. Org. Lett., 2011, 13, 6: 1486.
[12] Miao J M, Ge H B. Org. Lett., 2013, 15, 12: 2930.
[13] Wang J, Rosingana M, Watson D J, Discordia R P, Soundarajan N, Li W-S. Tetrahedron Letters, 2001 42: 8935.
[14] Tsuji J. Synthesis, 1984, 369.
[15] Lafrance M, Blaquiere N, Fagnou K. Chem. Commun., 2004, 2874.
[16] Leblanc M, Fagnou K. Org. Lett., 2005, 7, 14: 2849.
[17] Tomori H, Fox J M, Buchwald S L. J. Org. Chem., 2000, 65, 17: 5334.
[18] Vorogushin A V, Predeus A V, Wulff W D, Hansen H J. J. Org. Chem., 2003, 68, 15: 5826.
[19] Gauthier D R, Limanto J, Devine P N, Desmond R A, Szumigala R H J, Foster B S, Volante R P. J. Org. Chem., 2005, 70: 5938.
[20] Lafrance M, Gorelsky S I, Fagnou K. J. Am. Chem. Soc., 2007, 129, 47: 14570.
[21] Caron L, Campeau L C, Fagnou K. Org. Lett., 2008, 10, 20: 4533.
[22] Gaulier S M, McKay R, Swain N A. Tetrahedron Letters, 2011, 52(45): 6000.
[23] Kiser E J, Magano J, Shine R J, Chen M H. Org. Process Res. Dev., 2012, 16, 2: 255.
[24] Hennessy E J, Buchwald S L. J. Am. Chem. Soc., 2003, 125(40): 12084.
[25] 王勇(Wang Y), 程国林(Cheng G L), 崔秀灵(Cui X L). 有机化学(Chin. J. Org. Chem. ), 2012, 32: 2018.
[26] Campeau L C, Rousseaux S, Fagnou K. J. Am. Chem. Soc., 2005, 127: 18020.
[27] Youssif S. ARKIVOC, 2001, (i): 242.
[28] Leclerc J P, Fagnou K. Angew. Chem. Int. Ed., 2006, 45: 7781.
[29] Campeau L C, Bertrand-Laperle M, Leclerc J P, Villemure E, Gorelsky S, Fagnou K. J. Am. Chem. Soc., 2008, 130: 3276.
[30] Campeau L C, Sun H Y, Gorelsky S I, Stuart D R, Fagnou K. J. Org. Chem., 2010, 75: 8180.
[31] Campeau L C, Stuart D R, Leclerc J P, Bertrand-Laperle M, Villemure E, Sun H Y, Lasserre S, Guimond N, Lecavallier M, Fagnou K. J. Am. Chem. Soc., 2009, 131: 3291.
[32] Schipper D J, El-Salfiti M, Whipp C J, Fagnou K. Tetrahedron, 2009, 65: 4977.
[33] Quirk J, Thornton M, Kirkpatrick P. Nature, 2003, 2: 769.
[34] Capdeville R, Buchdunger E, Zimmermann J, Matter A. Nature, 2002, 1: 493.
[35] Friesen R W, Brideau C, Chan C C, Charleson S, DeschênesD, Dubé D, Ethier D, Fortin R, Gauthier J Y, Girard Y, Gordon R, Greig G M, Riendeau D, Savoie C, Wang Z, Wong E, Visco D, Xu L J, Young R N. Biorg. Med. Chem. Lett., 1998, 8, 2777.
[36] Campeau L C, Bertrand-Laperle M, Leclerc J P, Villemure E, Gorelsky S, Fagnou K. J. Am. Chem. Soc., 2008, 130: 3276.
[37] Ye M, Gao G L, Edmunds A J, Worthington P A, Morris J A, Yu J Q. J. Am. Chem. Soc., 2011, 133(47): 19090.
[38] Yokooji A, Okazawa T, Satoh T, Miura M, Nomura M. Tetrahedron, 2003, 59(30): 5685.
[39] Liegault B, Lapointe D, Caron L, Vlassova A, Fagnou K. J. Org. Chem., 2009, 74: 1826.
[40] Joo J M, Touré B B, Sames D. J. Org. Chem., 2010, 75: 4911.
[41] Shibahara F, Yamaguchi E, Murai T. Chem. Commun., 2010, 46: 2471.
[42] Shibahara F, Yamaguchi E, Murai T. J. Org. Chem., 2011, 76: 2680.
[43] Canivet J, Yamaguchi J, Ban I, Itami K. Org. Lett., 2009, 11, 8: 1733.
[44] Yamamoto T, Muto K, Komiyama M, Canivet J, Yamaguchi J, Itami K. Chem. Eur. J., 2011, 17: 10113.
[45] Kirchberg S, Tani S, Ueda K, Yamaguchi J, Studer A, Itami K. Angew. Chem. Int. Ed., 2011, 50, 10: 2387.
[46] Baran P S, Richter J M, Lin D W. Angew. Chem. Int. Ed., 2005, 44: 609.
[47] Jahn U, Harmann P. Chem. Commun., 1998, 2: 209.
[48] Besselivre F, Piguel S, Mahuteau-Betzer F, Grierson D S. Org. Lett., 2008, 10, 18: 4029.
[49] Xu X, Liu Y, Park C M. Angew. Chem. Int. Ed., 2012, 51: 9372.
[50] He G, Chen G. Angew. Chem. Int. Ed., 2011, 50: 5192.
[51] Muratake H, Hayakawa A, Natsume M. Tetrahedron Lett., 1997, 38: 7577.
[52] Martin C L, Overman L E, Rohde J M. J. Am. Chem. Soc., 2008, 130: 7568.
[53] Chaumontet M, Piccardi R, Baudoin O. Angew. Chem. Int. Ed., 2009, 48: 179.
[54] Kirmse W. Angew. Chem. Int. Ed. Engl., 1997, 36: 1164.
[55] Davies L, Beckwith J. Chem. Rev., 2003, 103: 2861.
[56] Astada M, Hashimoto S. Tetrahedron Letters, 1998, 39: 79.
[57] Anada M, Mita O, Watanabe H, Kitagaki S, Hashimoto S. Synlett, 1999, 1775.
[58] Axten J M, Ivy R, Krim L, Winkler J D. J. Am. Chem. Soc., 1999, 121, 27: 6511.
[59] Davies L, Stafford G, Hansen T. Org. Lett., 1999, 1, 2: 233.
[60] Davies L, Walji M, Townsend R J. Tetrahedron Lett., 2002. 43: 4981.
[61] Davies L, Gregg M, Tetrahedron Lett., 2002, 43(28): 4951.
[62] Davies L, Ni A. Chem. Commun., 2006, 3110.
[63] Taber D F, Neubert T D, Rheingold A L. J. Am. Chem. Soc., 2002, 124: 12416.
[64] Yun S Y, Zheng J C, Lee D. J. Am. Chem. Soc., 2009, 131: 8413.
[65] Kodama H, Katsuhira T, Nishida T, Hino T, Tsubata K. WO2001083421A1, 2001.
[66] Mei T S, Wang D H, Yu J Q. Org. Lett., 2010, 12(14): 3140.
[67] Xiao B, Gong T J, Xu J, Liu Z J, Liu L. J. Am. Chem. Soc., 2011, 133: 1466.
[68] Li Y, Ding Y J, Wang J Y, Wang X S. Org. Lett., 2013, 15(11): 2574.
[69] Woodward R B, Heusler K, Gosteli J, Naegeli P, Oppolzer W, Ramage R, Ranganathan S, Vorbruggen H. J. Am. Chem. Soc., 1966, 88, 4: 852.
[70] Wehn P M, Bois J D. J. Am. Chem. Soc., 2002, 124: 12950.
[71] McNeill E, Bois J D. J. Am. Chem. Soc., 2010, 132: 10202.
[72] Bullock K, Chong P, Davis R, Elitzin V, Hatcher M, Jackson M, Liu B, Patterson D, Powers J, Salmons M, Tabet E, Toczko M. Top Catal., 2012, 55: 446.
[73] 王晔峰(Wang Y F), 曾京辉(Zeng J H), 崔晓瑞(Cui X R). 有机化学(Chin. J. Org. Chem)., 2012, 32: 1041.

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