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| 研究生： |
王敏 Wang, Min |
|---|---|
| 論文名稱： |
一、使用高醯香豆素與 1,3-茚二酮衍生物進行 1,6-加成反應並透過有機不對稱試劑控制 Vinylogous Ketone Enolate 之 a/r-選擇性生成香豆素類似物
二、使用3-亞烷基羥吲哚衍生物對 1,3-茚二酮衍生物進行Vinylogous Michael/Acetalization/oxa-Michael/Michael 連續性反應合成含有五個四級碳中心的化合物 I. Controlling the /-Selectivity of Vinylogous Ketone Enolates in Organocatalytic Enantioselective 1,6-addition synthesis of two kinds of Coumarin analogues II. Enantioselective cascade for simultaneous generation of six stereocenters via Vinylogous Michael/Acetalization/oxa-Michael/Michael addition Cascade reaction |
| 指導教授： |
林文偉
Lin, Wen-Wei |
| 學位類別： |
碩士 Master |
| 系所名稱： |
化學系 Department of Chemistry |
| 論文出版年： | 2018 |
| 畢業學年度： | 106 |
| 語文別： | 中文 |
| 論文頁數： | 365 |
| 中文關鍵詞： | 有機合成 、不對稱催化 、四級碳立體中心 、串聯反應 、位置選擇性 |
| 英文關鍵詞： | Organic synthesis, Asymmetry catalysis, Quaternary stereocenter, Cascade reaction, Regioselectivity |
| DOI URL： | http://doi.org/10.6345/THE.NTNU.DC.007.2018.B05 |
| 論文種類： | 學術論文 |
| 相關次數： | 點閱：188 下載：1 |
| 分享至: |
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本研究以有機不對稱催化劑進行連續性反應，期能以之控制反應之化學選擇性及立體選擇性。利用金雞納鹼衍生物作為催化劑，以本實驗室開發之 1,3-茚二酮衍生物作為親電子性試劑與良好之親核性試劑進行有機催化串聯反應建構具有生物活性及化學應用潛能骨架之產物。
第一部分為利用高醯香豆素和β-酯基芳基亞烯基-1,3-茚二酮進行1,6-加成反應後，其高活性 dienolate 中間體可在反應條件控制下進行a/r-選擇性加成，得到兩種香豆素類似物之骨架。
第二部分為利用β-醯化-1,3-茚二酮衍生物和3-亞烷基羥吲哚衍生物使用接有硫脲片段的奎寧催化劑，在溫和的反應條件下，可進行 Vinylogous Michael addition / Acetalization / oxa-Michael addition / Michael addition 的不對稱串聯反應，產率最好可達 91% 、鏡像超越值98%，產物具有六個立體中心，其中的五個為四級碳結構。
In the present research, it is demonstrated that the chemoselectivity and the stereoselectivity of cascade reactions could be controlled by using a proper asymmetric organocatalyst in an efficient manner. Cinchonine derived tertiary amines were found to be suitable catalysts for the highly chemo and stereoselective cascade reaction between electrophilic 1,3-indanedione derivatives that were developed in our laboratory and different pronucleophiles to construct complex architectures that might have potential for biological as well as other chemical applications.
Part I：A regiodivergent cascade reaction involving 3-homoacylcoumarin and 2-arylallylidene-1,3-indanedione derivatives is demonstrated. By careful optimization of reaction conditions, we were able to achieve selective synthesis of two kinds of coumarin analogues.
Part II：A sequential vinylogous Michael / acetalization / oxa-Michael / Michael cascade is presented for the synthesis of product employing 3-alkylidene oxindole pronucleophile and 1,3-indanedione derived electrophile. The cascade product was obtained in excellent yield and good enantioselectivity (up to 91%, yield, up to 98% ee).
[1]Nguyen, L. A.; He, H.; Chuong, P.-H. Int. J. Biomed. Sci. 2006, 2, 85.
[2]Rentsch, K.M. J. Biochem. Biophys. Methods 2002, 54, 1.
[3]Cancer H.; Groner, E.; Levy, L.; Agranat, I. D.D.T. 2004 ,9, 101.
[4]Rouhi, A.M. Chem. Eng. News 2003, 81, 45.
[5]Vogel, A. Annal. d. Phyk. 1820, 64, 165.
[6] (a) Irie, M. Chem. Rev. 2000, 100, 1683. (b) Kuznetsova, N.A., Kaliya, O.L. Russ. Chem. Rev. 1992, 61, 683.
[7]Gebauer, M. Bioorg. Med. Chem. 2007, 15, 2414.
[8]Han, S.; Zhou, V.; Pan, S.; Liu, Y.; Hornsby, M.; McMullan, D.; Klock, H. E.; Haugen, J.; Lesley, S. A.; Gray, N.; Caldwell, J.; Gu, X. J. Bioorg. Med. Chem. Lett. 2005, 15, 5467.
[9](a) Heide, L. Biotechnology Advances. 2009, 27, 1006. (b) Gore, J.; Bryant, Z.; Stone, M.D.; Nöllmann, M.; Cozzarelli, N.R.; Bustamante, C. Nature. 2006, 439, 100.
[10]Ng, D.; Yang, Z.; Garcia-Garibay, M.A. Org. Lett. 2004, 6, 645.
[11]Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Ishihara, Y.; Maruyama, K. J Org. Chem. 1982, 47, 119.
[12]Hatano, M.; Mizuno, M.; Ishihara, K. Org. Lett. 2016, 18, 4462.
[13]Meng, F.; Li, X.; Torker, S.; Shi, Y.; Shen, X;, Hoveyda, A.H. Nature 2016, 537, 387.
[14](a) Dell'Amico, L.; Albrecht, L.; Naicker, T.; Poulsen, P.H.; Jørgensen, K.A. J. Am. Chem. Soc. 2013, 135, 8063. (b) Feng, J.; Li, X.; Cheng, J.-P. J. Org. Chem. 2017, 82, 1412.
[15]Tian, X.; Liu, Y.; Melchiorre, P. Angew. Chem. Int. Ed. 2012, 51, 6439.
[16]Bernardi, L.; López-Cantarero, J.; Niess, B.; Jørgensen, K.A. J. Am. Chem. Soc. 2007, 129, 5772.
[17]Chu, W.-D.; Zhang, L.-F.; Bao, X.; Zhao, X.-H.; Zeng, C.; Du, J.-Y.; Zhang, G.-B.; Wang, F.-X.;n Ma, X.-Y.; Fan, C.-A. Angew. Chem. 2013, 125, 9229.
[18]Zhao, K.; Zhi, Y.; Wang, A.; Enders, D. ACS Catal. 2016, 6, 657.
[19]Brooks, J. L.; Caruana, P. A.; Frontier, A. J. J. Am. Chem. Soc. 2011, 133, 12454.
[20]Chang, F.-J.; Gurubrahamam, R.; Chen, K. Adv.Synth. Catal. 2017, 359, 1277.
[21]Zhu, T.; Mou, C.; Li, B.; Smetankova, M.; Song, B.-A.; Chi, Y.R. J. Am. Chem. Soc. 2015, 137, 5658.
[22]Katzenellenbogen, J.A.; Crumrine, A.L. J. Am. Chem. Soc. 1976, 98, 4925.
[23]Liu, Y.; Liu, J.; Huang, Y.; Qing, F.-L. Chem. Commun. 2013, 49, 7492.
[24]Manuscript is under preparation.
[25]Li, W.; Han, Y.; Chen, J. Tetrahedron 2017, 39, 5813.
[26]A. K. Awasthi; R. S. Tewari Synthesis 1986, 12, 1061.
[27]Ye, N.; Chen, H.; Wold, E. A.; Shi, P.-Y.; Zhou, J. ACS Infect. Dis. 2016, 2, 382.
[28]Wang, Q.-Y.; Dong, H.; Zou, B.; Karuna, R.; Wan, K.F.; Zou, J.; Susila, A.; Yip, A.; Shan, C.; Yeo, K.L.; Xu, H.; Ding, M.; Chan, W.L.; Gu, F.; Seah, P.G.; Liu, W.; Lakshminarayana, S.B.; Kang, C.; Lescar, J.; Blasco, F.; Smith, P.W.; Shi, P.-Y. J. Virol. 2015, 89, 8233.
[29]Jiang, T.; Kuhen, K.L; Wolff, K.; Yin, H.; Bieza, K.; Caldwell, J.; Bursulaya, B.;
Tuntland, T.; Zhang, K.; Karanewsky, D.; He, Y. Bioorg. Med. Chem. Lett. 2006, 16, 2105.
[30]Kurbatov, S.V.; Zarubaev, V.V.; Karpinskaya, L.A.; Shvets, A.A.; Kletsky, M.E.; Burov, O.N.; Morozov, P.G.; Kiselev, O.I.; Minkin, V.I. Russ. Chem. Bull. 2014, 63, 1130.
[31]Yang, J.; Wearing, X. Z.; Le Quesne, P. W.; Deschamps, J. R.; Cook, J. M. J. Nat. Prod. 2008, 71, 1431.
[32]Trost, B.M.; Cramer, N.; Bernsmann, H. J. Am. Chem. Soc. 2007, 129, 3086.
[33]Fonseca, G.O., Wang, Z.-J., Namjoshi, O.A., Deschamps, J.R., Cook, J.M. Tetrahedron Lett. 2015, 56, 3052.
[34]Cheng, D.; Ishihara, Y.; Tan, B.; BarbasIII, C. F. ACS Catal. 2014, 4, 743.
[35](a) MacMillan, D.W.C. Nature 2008, 455, 304. (b) Deiana, L.; Afewerki, S.; Palo-Nieto, C.; Verho, O.; Johnston, E.V.; Córdova, A. Sci. Rep. 2012, 2, 851.
[36]Volla, C.M.R.; Atodiresei, I.; Rueping, M. Chem. Rev. 2014, 114, 2390.
[37](a) Companyó, X.; Zea, A.; Alba, A.-N. R.; Mazzanti, A.; Moyano, A.; Rios, R.
Chem. Commun. 2010, 46, 6953. (b) Cassani, C.; Tian, X.; Escudero-Adán, E. C.; Melchiorre, P. Chem. Commun. 2011, 47, 233.
[38]Mao, Z.; Jia, Y.; Xu, Z.; Wang, R. Adv. Synth. Catal. 2012, 354, 1401.
[39]Wang, Y.; Yu, D.-F.; Liu, Y.-Z.; Wei, H.; Luo, Y.-C.; Dixon, D.J.; Xu, P.-F. Chem. Eur. J. 2010, 16, 3922.
[40]Chen, W.-B.; Wu, Z.-J.; Pei, Q.-L.; Cun, L.-F.; Zhang, X.-M.; Yuan, W.-C. Org. Lett. 2010, 12, 3132.
[41]Ramachary, D. B.; Venkaiah, C.; Krishna, P. M. Chem. Commun. 2012, 48, 2252.
[42]Rueping, M., Antonchick, A.P. Angew. Chem. Int. Ed. 2008, 47, 5836.
[43](a) Jiang, K.; Jia, Z.-J.; Yin, X.; Wu, L.; Chen, Y.-C. Org. Lett. 2010, 12, 2766. (b) Kotame, P.; Hong, B.-C.; Liao, J.-H. Tetrahedron Lett. 2009, 50, 704. (c) Enders, D.; Greb, A.; Deckers, K.; Selig, P.; Merkens, C. Chem.—Eur. J. 2012, 18, 10226.
[44]Enders, D.; Wang, C.; Mukanova, M.; Greb, A. Chem. Commun. 2010, 46, 2447.
[45]Rueping, M.; Haack, K. L.; Ieawsuwan, W.; Sunden, H.; Blanco, M.; Schoepke, F. R. Chem. Commun. 2011, 47, 3828.
[46]Yang, M.-S.; Reddy, M.G; Wang, P.-T.; Yeh S.-Y; Wang M.; Lin W.-W. Chem Commun. 2017, 53, 7649.
[47]Casiraghi, G.; Zanardi, F.; Appendino, G.,;Rassu, G. Chem. Rev. 2000, 100, 1929.
[48]Han, J.-L.; Chang, C.-H. Chem. Commun. 2016, 52, 2322.
[49]Möhlmann, L.; Chang, G.-H.; Madhusudhan Reddy, G.; Lee, C.-J.; Lin, W. Org. Lett. 2016, 18, 688.
[50]Feng, J.; Li, X. J. Org. Chem. 2017, 82, 7317.
[51]Xie, J.W.; Chen, W.; Li, R.; Zeng, M.; Du, W.; Yue, L.; Chen, Y.-C.; Wu, Y.; Zhu, J.; Deng, J.-G. Angew.Chem. Int.Ed. 2007, 46, 389.
[52]Gu, X.; Guo, T.; Dai, Y.; Franchino, A.; Fei, J.; Zou, C.; Dixon, D.J.; Ye, J. Angew.Chem. Int.Ed. 2015, 54, 10249.
[53]Feng, J.; Li, X.; Cheng, J.-P. J. Org. Chem. 2017, 82, 1412.
[54]Xiao, X.; Mei, H.; Chen, Q.; Zhao, X.; Lin, L.; Liu, X.; Feng, X. Chem. Commun. 2015, 51, 580.
[55]Chen, Q.; Wang, G.; Jiang, X.; Xu, Z.; Lin, L.; Wang, R. Org. Lett. 2014, 16, 1394.
[56]Lee, C.-J.; Sheu, C.-N.; Tsai, C.-C.; Wu, Z.-Z.; Lin, W. Chem. Commun 2014, 50, 5304.
[57]葉宇盛 “106學年度國立臺灣師範大學化學系碩士論文”
[58]Han, J.-L.; Tsai, Y.-D.; Chang, C.-H. Adv. Synth. Catal. 2017, 359, 4043.
