摘要
有机合成的本质是有机分子旧键的断裂和新键的生成,主要包括碳-碳、碳-杂原子原子键的生成。通常来说,亲电性饱和碳(sp3杂化)和亲核性碳、氮、氧、硫等原子之间可以直接反应生成相应的碳-碳、碳-杂原子原子键；而亲电性不饱和碳(sp或sp2杂化)与亲核性碳或杂原子的直接反应成键则相对比较困难。近年来逐渐发展起来的交叉偶联反应(Cross-Coupling Reactions)和Conia-Ene反应则是不饱和碳与亲核性碳或杂原子成键的新方法。
2003年,Li Chao-Jun课题组首次报道了金催化的三组分偶联反应。随后则在不同的文献中报道了铜、银、金、铟等金属以及金纳米颗粒、铜纳米颗粒、铁纳米颗粒等催化的三组分偶联反应。本论文中,详细研究了氧化银纳米颗粒催化的三组分偶联反应。由于氧化银纳米颗粒在空气中稳定存在,因此反应无需氮气保护即可进行。通过条件的优化,确定了常温下三氯甲烷中即可进行反应。随后,我们将该反应应用于不同的醛和胺的底物拓展中,取得了令人满意的效果。而催化剂经过简单处理循环使用数次后,产率未见明显下降,说明催化剂的活性并未明显降低。由于氧化银纳米颗粒合成简单,容易分离,而反应条件简单,迅速快捷,符合绿色化学的要求,可以将这种方法应用于炔丙胺的合成。
另外,从上个世纪八十年代,科学家们致力于研究金属催化的Conia-Ene反应,逐渐发展了铝、钯、金、铟等金属催化剂来催化反应的进行,取得了不同程度的效果。本论文中,详细研究了一价铜催化剂催化的Conia-Ene反应。由于一价铜易被氧化,因此反应需在氩气保护下进行。通过条件的优化,确定了CuOTf作为催化剂,AgBF4作为辅助银盐,在1,2-二氯乙烷中80℃下反应可以得到目标产物。然而反应产率偏低,不利于底物拓展,需要寻找更好的条件来提高产率,相关研究仍在进行中。
Organic synthesis, breaking the old organic bonds and forming the new bonds, is the process of preparing complex organic compounds through the formation of carbon-carbon bond and functional group transformation of small molecular compounds. Generally speaking, the electrophilic saturated carbon (sp3) can form corresponding carbon-carbon, carbon-heteroatom bonds directly with the nucleophilic carbon, nitrogen, oxygen, sulfur atoms, while the direct bond formation of electrophilic unsaturated carbon (sp or sp2) is relatively difficult. In recent years, as a new approach to form the bond between the unsaturated carbon and nucleophilic carbon or heteroatom, the Cross-Coupling Reactions and Conia-Ene Reactions were developed.
In2003, Li Chao-Jun's group reported the gold-catalyzed three-component coupling reaction for the first time. Then, various three-component coupling reactions catalyzed by copper, silver, gold, indium and gold nanoparticles, copper nanoparticles, iron nanoparticles, and so on were reported in diverse literatures.
In this thesis, we studied the silver-nanoparticles catalyzed three-component coupling reaction which can be carried out without the nitrogen atmosphere since silver nanoparticles are stable in the air. Through the optimization of the reaction conditions, we confirmed that the reactions can be carried in chloroform at room temperature. Subsequently, a variety of propargylamines are prepared from various aldehydes, alkynes, and amines using the optimized reaction conditions to expand the scope of the substrates, and satisfactory results were achieved. After simple purification, the catalyst can be reused several times without significant loss of yield, which indicates that the activity of the catalyst is not significantly reduced. The silver nanoparticles can be readily synthesized and separated, and the reactions are rapid and efficient under wild conditions. This method meets the requirements of green chemistry, and it can be applied for the synthesis of propargylamines.
On the other hand, from1980s, scientists were working on metal-catalyzed Conia-Ene reactions. They developed various metal catalysts such as aluminum, palladium, gold, indium and so on to catalyze the Conia-Ene reactions, and achieved various degrees of success. In this thesis, we tested copper(Ⅰ) compounds catalyzed Conia-Ene reactions. The reaction was carried out under argon atmosphere since the copper(Ⅰ) compounds can be easily oxidized in the air. After optimization, the target product can be obtained by using CuOTf as a catalyst, and AgBF4as an additive, at80℃in1,2-dichloroethane. However, the reaction yield is still low, and it is not beneficial to expand the scope of the substrates. Therefore, we need to find better conditions to improve the yield, and the related work is still in progress.
引文
[1](a) Tamao, K.; Miyaura, N. Topics in Current Chemistry 2002,219,1; (b) Prim, D.;Campagne, J. M. Tetrahedron 2002,55,2041; (c) Terao, J.; Kambe, N. Acc. Chem. Res.2008,41,1545.
[2](a) Negishi, E. Acc. Chem. Res.1982,12,349; (b) Murahashi, S. I.; Davies, S. G. Blackwell Science,1999.
[3](a) Toyota, M.; Komori, C.; Ihara, U. J. Org. Chem.2000,65,7110; (b) Paterson, I.; Davies, R. D. M.; Marquez, R. Angew. Chem. Int. Ed.2001,40,603; (c) Haddad, N.; Farina, V. J. Org. Chem.2006,71,5031; (d) Ding, Q.; Wang, B.; Wu, J.; Tetrahedron Lett.2007,48,8599; (e) Bunz, U. H. F. Chem. Rev.2000,100,1605.
[4](a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.1915,16,4467; (b) Sonogashira, K. Comp. Org. Synth.1991,3,521; (c) Pierre, G. J. J. Organomet. Chem. 1999,576,305; (d) Negishi E. J. Organomet. Chem.2002,653,34.
[5](a) Multicomponent Reactions; Zhu, J.,Bienayme, H., Eds.; Wiley:Weinheim, 2005; (b) Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc. Chem. Res.1996,29,123.
[6](a) Miura, M.; Enna, M.; Okuro, K.; Nomura, M. J. Org. Chem.1995,60,4999; (b) Naota, I.; Takaya, H.; Murahashi, S. I. Chem. Rev.1998,98,2599.
[7](a) Li, C. J. Acc. Chem. Res.2009,42,335; (b) Li, Z.; Li, C. J. J. Am. Chem. Soc. 2005,127,3672.
[8]Wei, C. M.; Li, C. J. J. Am. Chem. Soc.2003,125,9584.
[9]Gommarman, N.; Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed. 2003,42,5763.
[10]Wei, C. M.; Li, Z. G.; Li, C. J. Org. Lett.2003,5,4473.
[11]Shi, L.; Tu, Y. Q.; Wang, M.; Zhang, F. M.; Fan, C. A. Org. Lett.2004,6,1001.
[12]Li, Z. G.; Wei, C. M.; Chen, L.; Varma, R. S.; Li, C. J. Tetrahedron Lett.2004,45, 2443.
[13]Park, S. B.; Alper, H. Chem. Commun.2005,10,1315.
[14]Choudary, B. M.; Sridhar, C.; Kantam, M. L.; Sreedhar, B. Tetrahedron Lett. 2004,45,7319.
[15]Lo, V. K. Y; Liu, Y. G.; Wong, M. K.; Che, C. M. Org. Lett.2006,8,1529.
[16]Aschwanden, P.; Stephenson, C. R. J.; Carreira, E. M. Org. Lett.2006,8,2437.
[17]Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green Chem.2007,9,742.
[18]Kidwai, M.; Bansal, V.; Mishra, K. N.; Kumar, A.; Mozumdar, S. Synlett 2007, 10,1581.
[19]Li, P. H.; Wang, L.; Zhang, Y. C.; Wang, M. Tetrahedron Lett.2008,49,6650.
[20]Li, P. H.; Wang, L. Tetrahedron 2007,63,5455.
[21]Likhar, P. R.; Roy, S.; Subhas, M. S.; Kantam, M. L.; Lai De R.; Synlett 2007,14, 2301.
[22]Patil, M. K.; Keller, M.; Reddy, B. M.; Pale, P.; Sommer, J. Eur. J. Org. Chem. 2008,4440.
[23]Mukhopadhyay, C.; Rana. S. Catal. Commun.2009,11,285.
[24]Zhang, Y C.; Li, P. H.; Wang, M.; Wang, L. J. Org. Chem.2009,74,4364.
[25]Namitharan, K.; Pitchumani, K. Eur. J. Org. Chem.2010,411.
[26]Dou, X. Y.; Shuai, Q.; He, L. N.; Li, C. J. Adv. Synth. Catal.2010,352,2437.
[27]Chen, W. W.; Nguyen, R. V.; Li, C. H. Tetrahedron Lett.2009,50,2895.
[28]Li, P. H.; Zhang, Y. C.; Wang, L. Chem. Eur. J.2009,15,2045.
[29](a) Zeng, T. Q.; Chen, W. W.; Cirtiu, C. M.; Moores, A.; Li, C. J. Green Chem. 2010,12,570; (b) Sreedhar, B.; Kumar, A. S.; Reddy, P. S. Tetrahedron Lett.2010,51, 1891.
[30]Zhao, Y.; Zhou, X.; Okamura, T.; Chen, M.; Lu, Y.; Sun, W. Y.; Yu, J. Q. Dalton Trans.2012,47,5889.
[31]Eglinton, G.; Whiting, M. C. J. Chem. Soc.1953,3052.
[32]Conia, J. M.; Perchec, P. L. Synthesis 1975,1,1.
[33](a) Snider, B.B.; Karras, M.; Price. R.T.; Rodini. D.J. J.Org.Chem.1982,47,4538; (b) Jackson, A. C.; Goldman, B. E.; Snider, B. B. J.Org.Chem.1984,49,3988.
[34]Monteiro, N.; Hemelryck, B. V.; Balme, G. Synlett 1994,6,447.
[35]Monteiro, N.; Gore, J.; Balme, G. Tetrahedron 1992,48,10103.
[36]Yang, D.; Li, J. H.; Gao, Q.; Yan, Y. L. Org. Lett.2003,5,2869.
[37]Corkey, B. K.; Toste, F. D. J. Am. Chem. Soc.2005,127,17168.
[38]Duan, X. H.; Guo, L. N.; Bi, H. P.; Liu, X. Y.; Liang, Y. M. Org. Lett.2006,8, 5777.
[39]Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc.2004,126, 4526
[40]Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem. Int. Ed.2004,43, 5350.
[41]Mezailles, N.; Ricard, L.; Gagosz, F. Org. Lett.2005,7,4133.
[42]Pan, J. H.; Yang, M.; Gao, Q.; Zhu, N. Y.; Yang, D. Synthesis 2007,16,2539.
[43]Ito, H.; Makida, Y; Ochida, A.; Ohmiya, H.; Sawamura, M. Org. Lett.2008,10, 5051.
[44]Tsuji, H.; Yamagata, K.; Itoh, Y.; Endo, K.; Nakamura, M.; Nakamura, E. Angew. Chem. Int. Ed.2007,46,8060.
[45]Endo, K.; Hatakeyama, T.; Nakamura, M; Nakamura, E. J. Am. Chem. Soc.2007, 129,5264.
[46]Itoh, Y.; Tsuji, H.; Yamagata, K.; Endo, K.; Tanaka, I.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc.,2008,130,17161.
[47]Takahashi, K.; Midori, M.; Kawano, K.; Ishihara, J.; Hatakeyama, S. Angew. Chem. Int. Ed.2008,47,6244.
[48]Monteiro, N.; Balme, G.; Gore, J. Synlett 1992,3,227.
[49]Bouyssi, D.; Monteiro, N.; Balme, G Tetrahedron Lett.1999,40,1297.
[50]Gao, Q.; Zheng, B. F.; Li, H. H.; Yang, D. Org. Lett.2005,7,2185.
[51]Gou, F. R.; Bi, H. P.; Guo, L. N.; Guan, Z. H.; Liu, X. Y; Liang, Y M. J. Org. Chem.2008,73,3837.
[52]Cruciani, P.; Stammler, R.; Aubert, C.; Malacria, M. J. Org. Chem.1996,61, 2699.
[53]Kitagawa, O.; Suzuki, T.; Inoue, T.; Watanabe, Y.; Taguchi, T. J. Org. Chem. 1998,63,9470.
[54]Kuninobu, Y.; Kawata, A.; Takai, K. Org. Lett.2005,7,4823.
[55]Kuninobu, Y.; Nishi, M.; Kawata, A.; Takata, H.; Hanatani, Y.; Yudha, S. S.; Iwai, A.; Takai, K. J. Org. Chem.2010,75,334.
[56]Zhao, W. G.; Hua, R. M. Tetrahedron 2007,63,11803.
[1](a) Samai, S.; Nandi, G. C.; Singh, M. S. Tetrahedron Lett.2010,51,5555; (b) Park, S. B.; Alper, H. Chem. Commun.2005,1315; (c) Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green Chem.2007,9,742; (d) Zhang, Y. C.; Li, P. H.; Wang, M.; Wang, L. J. Org. Chem.2009,74,4364; (e) Wei, C. M.; Li, Z. G.; Li, C. ]. Org. Lett.2003,5,4473.
[2]Murai, T.; Mutoh, Y.; Ohta, Y.; Murakami, M. J. Am. Chem. Soc.2004,126,5968.
[3](a) Gommarman, N.; Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed. 2003,42,5163; (b) Dou, X. Y.; Shuai, Q.; He, L. N.; Li, C. J. Adv. Synth. Catal. 2010,352,2437.
[4](a) Wei, C. M.; Li, Z. G.; Li, C. J. Org. Lett.2003,5,4473; (b) Li, Z. G.; Wei, C. M.; Chen, L.; Varma, R. S.; Li, C. J. Tetrahedron Lett.2004,45,2443.
[5](a) Wei, C. M.; Li, C. J. J. Am. Chem. Soc.2003,125,9584; (b) Lo, V. K. Y.; Liu, Y G; Wong, M. K.; Che, C. M. Org. Lett.2006,8,1529.
[6]Zhang, Y C.; Li, P. H.; Wang, M.; Wang, L.J. Org. Chem.2009,74,4364
[7]Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green Chem.2007,9,742.
[8]Kidwai, M.; Bansal, V.; Mishra, K. N.; Kumar, A.; Mozumdar, S. Synlett 2007,10, 1581.
[9](a) Zeng, T. Q.; Chen, W. W.; Cirtiu, C. M.; Moores, A.; Li, C. J. Green Chem. 2010,12,570; (b) Sreedhar, B.; Kumar, A. S.; Reddy, P. S. Tetrahedron Lett.2010, 57,1891.
[10](a) Wang, X., Wu, H. F., Kuang, Q., Huang, R. B., Xie, Z. X., Zheng, L. S. Langmuir 2010,26,211 A; (b) Lyu, L. M., Wang, W. C, Huang, M. H. Chem. Eur. J. 2010,16,14167.
[1](a) Snider, B.B.; Karras, M.; Price. R.T.; Rodini. D.J. J.Org.Chem.1982,47,4538. (b) Jackson, A. C.; Goldman, B. E.; Snider, B. B. J.Org.Chem.1984,49,3988.
[2](a) Monteiro, N.; Hemelryck, B. V.; Balme, G. Synlett 1994,6,447; (b) Monteiro, N.; Gore, J.; Balme, G. Tetrahedron 1992,48,10103.
[3](a) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc.2004,126, 4526; (b) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem. Int. Ed. 2004,43,5350.
[4](a) Tsuji, H.; Yamagata, K.; Itoh, Y.; Endo, K.; Nakamura, M.; Nakamura, E. Angew. Chem. Int. Ed.2007,46,8060; (b) Endo, K.; Hatakeyama, T.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc.2007,129,5264; (c) Itoh, Y.; Tsuji, H.; Yamagata, K.; Endo, K.; Tanaka, I.; Nakamura, M; Nakamura, E. J. Am. Chem. Soc.,2008,130, 17161.