簡易檢索 / 詳目顯示

回結果列表
研究生： 張怡雅
Chang, Yi-Ya
論文名稱： 多取代雙螺環己烷之有機催化Rauhut-Currier連鎖反應
Rauhut-Currier-Initiated Organocascade Reaction: Synthesis of Substituted Dispirocyclohexanes through a [2+2+2] Strategy Between 2-Arylideneindan-1,4-diones and Activated Alkenes
指導教授： 陳焜銘
Chen, Kwun-Min
學位類別： 碩士
Master
系所名稱： 化學系
Department of Chemistry
論文出版年： 2015
畢業學年度： 103
語文別： 中文
論文頁數： 156
中文關鍵詞： 碳－碳共價鍵 、有機催化連鎖反應 、Rauhut-Currier耦合反應 、2-芳香環亞甲基二氫茚-1,3-二酮 、活化烯類 、二螺環己烷
英文關鍵詞： carbon－carbon bond formation, organocascade reaction, Rauhut-Currier coupling reaction, 2-arylideneindan-1,3-diones, activated alkenes, dispirocyclohexane
論文種類： 學術論文
相關次數： 點閱：112  下載：1 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 中文摘要
    合成化學家透過碳—碳共價鍵之生成，擴張分子架構，製備含有多重官能基、具應用性、生物活性的化合物單元。有機催化連鎖反應於近年來，被視為高效能、低成本兼具綠色化學概念的合成策略，經由簡單的操作，伴隨多重鍵結之生成，建構連續的立體化學中心；另一方面，Rauhut-Currier耦合反應憑藉共軛加成，產生的親核兩性離子烯醇鹽，與親電子試劑進行Michael加成反應，合成出高度官能基化的耦合產物。本實驗結合有機催化連鎖合成策略及Rauhut-Currier耦合反應，發展以2-芳香環亞甲基二氫茚-1,3-二酮及活化烯類為起始物的有機催化連鎖環化反應，在路易士鹼1,4-二氮雜二環[2.2.2]辛烷（20 mol %）及鹼試劑碳酸氫鈉（20 mol %）的共催化下，乙腈作為溶劑，反應濃度為0.1 M，於室溫的環境進行反應。隨後以傑出的產率（54-99%）及優異的非鏡像選擇性（>95:5 d.r. in all cases），分離出具有剛性架構的多取代、全取代二螺環己烷衍生物，在此有機催化連鎖反應中，建構三個碳—碳共價鍵的同時，亦建立三個以上的立體化學中心，以及兩個螺接碳原子。

    關鍵字：碳—碳共價鍵、有機催化連鎖反應、Rauhut-Currier耦合反應、2-芳香環亞甲基二氫茚-1,3¬-二酮、活化烯類、二螺環己烷。

    Abstract
    In order to construct highly-functionalized, biologically-active, applicable synthons, synthetic chemists expand the structural framework by exploitation of formation of carbon—carbon bonds. Presently, organocascade reaction is regarded as a powerful, efficient, low-cost synthetic strategy, which is especially performed in an environmentally-friendly fashion. Formation of multiple covalent bonds is followed by concurrent construction of stereocenters under the simplest manipulation. Additionally, Rauhut-Currier coupling reaction takes advantage of nucleophilic zwitterionic enolate resulting from conjugate addition between Lewis base and activated alkene. Afterward Michael addition between nucleophilic zwitterionic enolate and electrophile furnishes coupling product with multi-functionalities. Herein, combination of organocascade strategy and Rauhut-Currier coupling concept leads to the [2+2+2]annulation between 2-arylideneindan-1,3-diones and activated alkenes. In the presence of 1,4-diazabicyclo[2.2.2]octane and sodium bicarbonate, the Rauhut-Currier-initiated organocascade reaction proceeds well in acetonitrile solution at ambient temperature to afford highly-strained multi- and fully-substituted dispirocyclohexanes in excellent chemical yields (54-99%), with impressive diastereoselecivities (>95:5 d.r.). Formation of three carbon—carbon covalent bonds with simultaneous construction of multiple stereogenic centers and two spirocarbon atoms is accomplishable in this desirable organocascade reaction.

    Keywords：carbon－carbon bond formation、organcascade reaction、Rauhut-Currier coupling reaction、2-Arylideneindan-1,3-dione、activated alkene、dispirocyclohexane.

    第一章 緒論 1 1-1 前言 1 1-2 常見之有機催化模式 2 1-2-1 共價催化 5 1-2-2 非共價催化 18 1-3 有機催化劑應用於碳—碳共價鍵之建構 22 1-3-1 Morita-Baylis-Hillman耦合反應 22 1-3-2 Rauhut-Currier耦合反應 25 1-4 有機催化連鎖反應 30 1-4-1 有機共價催化連鎖反應 31 1-4-2 有機非共價催化連鎖反應 36 1-5 本實驗室於有機催化連鎖反應暨環己烷衍生物之相關合成 37 1-6 研究動機 39 第二章 實驗結果與討論 41 2-1 有機催化致螺環己烷之合成 41 2-2 有機催化分子間Rauhut-Currier耦合反應 41 2-2-1 非手性親核性催化劑之篩選 42 2-2-2 反應溶劑之篩選 43 2-2-3 酸鹼添加劑之篩選 45 2-2-4 最佳反應濃度及當量數之探索 46 2-2-5 取代基效應 47 2-2-6 多取代二螺環己烷產物之結構鑑定與解析 49 2-2-7 反應機構的探討 52 2-2-8 結論 53 第三章 實驗部分 55 3-1 分析儀器及基本實驗操作 55 3-2 有機催化Rauhut-Currier連鎖[2+2+2]環化反應之實驗步驟 57 3-3 光譜數據 58 第四章 參考文獻 73 附錄一、1H NMR、13C NMR及19F NMR光譜圖 79 附錄二、X-ray單晶繞射結構解析及數據 121

    1. http://en.wikipedia.org/wiki/Chemical_bond
    2. http://en.wikipedia.org/wiki/Covalent_bond
    3. http://en.wikipedia.org/wiki/Sigma_bond
    4. Wade, L. G. Jr. Organic Chemistry. 8th ed.; Pearson Education Inc.: United States of America, 2013.
    5. http://en.wikipedia.org/wiki/Organic_chemistry
    6. Koshland, D. E. Jr. Proc. Natl. Acad. Sci. U.S.A. 1958, 44, 98.
    7. List, B.; Lerner, R. A.; Barbas, C. F. III. J. Am. Chem. Soc. 2000, 122, 2395.
    8. Zimmerman, H. E.; Traxler, M. D. J. Am. Chem. Soc. 1957, 79, 1920.
    9. Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243.
    10. Lelais, G.; MacMillan, D. W. C. Aldrichimica Acta 2006, 39, 79.
    11. List, B. J. Am. Chem. Soc. 2000, 122, 9336.
    12. Zhong, G. Angew. Chem. Int. Ed. 2003, 42, 4247.
    13. Bøgevig, A.; Juhl, K.; Kumaragurubaran, N.; Zhuang, W.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2002, 41, 1790.
    14. Betancort, J. M.; Barbas, C. F. III Org. Lett. 2001, 3, 3737.
    15. Beeson, T. D.; Macmillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 8826.
    16. List, B. Chem. Commun. 2006, 819.
    17. Marigo, M.; Franzén, J.; Poulsen, T. B.; Zhuang, W.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 6964.
    18. Kunz, R. K.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 3240.
    19. Beeson, T. D.; Mastracchio, A.; Hong, J.-B.; Ashton, K.; MacMillan, D. W. C. Science 2007, 316, 582.
    20. Devery, J. J., III, Conrad, J. C.; MacMillan, D. W. C.; Flowers, R. A., II. Angew. Chem. Int. Ed. 2010, 49, 6106.
    21. Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606.
    22. Wöhler, F.; Liebig, J. Ann. Pharm. 1832, 3, 249
    23. Ugai, T.; Tanaka, S.; Dokawa, S. J. Pharm. Soc. Jpn. 1943, 63, 296.
    24. Breslow, R. J. Am. Chem. Soc. 1958, 80, 3719.
    25. Sheehan, J. C.; Hunneman, D. H. J. Am. Chem. Soc. 1966, 88, 3666.
    26. Sheehan, J. C.; Hara, T. J. Org. Chem. 1974, 39, 1196.
    27. Enders, D.; Kallfass, U. Angew. Chem. Int. Ed. 2002, 41, 1743.
    28. Dudding, T.; Houk, K. N. Proc. Natl. Acad. Sci. 2004, 101, 5770.
    29. Stetter, H.; Schreckenberg, M. Angew. Chem. 1973, 85, 89.
    30. Stetter, H. Angew. Chem. Int. Ed. Engl. 1976, 15, 639.
    31. Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Angew. Chem. Int. Ed. 2004, 43, 1566.
    32. Yamanaka, M.; Itoh, J.; Fuchibe, K.; Akiyama, T. J. Am. Chem. Soc. 2007, 129, 6756.
    33. Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126, 5356.
    34. Seayad, J.; Seayad, A. M.; List, B. J. Am. Chem. Soc. 2006, 128, 1086.
    35. Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125, 12672.
    36. Okino, T.; Hoashi, y.; Furukawa, T.; Xu, X.; Takemoto, Y. J. Am. Chem. Soc. 2005, 127, 119.
    37. Taylor, M. S.; Tokunaga, N.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2005, 44, 6700.
    38. (a) Morita, .K; Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn. 1968, 41, 2815.
    (b) Morita, K. Japan Patent, 6803364, 1968.
    39. (a) Baylis, A. B.; Hillman, M. E. D. German Patent 2155113, 1972.; Chem. Abstr. 1972, 77, 34174q.
    40. (a) Drewes, S. E.; Emslie, N. D. J. Chem. Soc., Perkin Trans. 1 1982, 2079.
    (b) Hoffman, H. M. R.; Rabe, J. Angew. Chem. Int. Ed. Engl. 1983, 22, 795.
    (c) Hoffman, H. M. R.; Rabe, J. Helv. Chim. Acta 1984, 67, 413.
    (d) Basavaiah, D.; Gowriswari, V. V. L. Tetrahedron Lett. 1986, 27, 2031.
    41. Aggarwal, V. K.; Tarver, G. J.; McCague, R. Chem. Commun. 1996, 2713.
    42. Aggarwal, V. K.; Mereu, A.; Tarver, G. J; McCague, R. J. Org. Chem. 1998, 63, 7183.
    43. Rafel, S.; Leahy, J. W. J. Org. Chem. 1997, 62, 1521
    44. Coelho, F.; Almeida, W. P.; Veronese, D.; Mateus, C. R.; Lopes, E. C. S.; Rossi, R. C.; Silveira, G. P. C.; Pavam, C. H. Tetrahedron 2002, 58, 7437.
    45. Hayashi, Y.; Okado, K.; Ashimine, I.; Shoji, M. Tetrahedron Lett. 2002, 43, 8683.
    46. Cablewski, T.; Faux, A. F.; Strauss, C. R. J. Org. Chem. 1994, 59, 3408.
    47. Kawamura, M.; Kobayashi, S. Tetrahedron Lett. 1999, 40, 1539
    48. Aggarwal, V. K.; Dean, D. K.; Mereu, A.; Williams, R. J. Org. Chem. 2002, 67, 510.
    49. For recent review articles on asymmetric MBH coupling reaction, see:
    (a) Basavaiah, D.; Rao, A. J; Satyanarayana, T. Chem. Rev. 2003, 103, 811.
    (b) Basavaiah, D.; Rao, K. V.; Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581.
    (c) Masson, G.; Housseman, C.; Zhu, J. Angew. Chem. Int. Ed. 2007, 46, 4614.
    (d) Wei, Y.; Shi, M. Chem .Rev. 2013, 113, 6659
    50. Drews, S. E.; Manickum, T. Roos, G. H. P. Synth. Commun. 1988, 18, 1065.
    51. Gilbert, A.; Heritage, T. W.; Isaacs, N. S. Tetrahedron: Asymmetry 1991, 2, 969.
    52. Manickum, T.; Roos, G. Synth. Commun. 1991, 21, 2269.
    53. Kündig, E. P; Xu, L. H.; Romanens, P.; Bernardinelli, G. Tetrahedron Lett. 1993, 34, 7049.
    54. Bauer, T.; Tarasiuk, J. Tetrahedron: Asymmetry 2001, 12, 1741.
    55. Brzezinski, L. J.; Rafel, S.; Leahy, J. W. J. Am. Chem. Soc. 1997, 119, 4317.
    56. Yang, K.-S.; Chen, K. Org. Lett. 2000, 2, 729.
    57. Jauch, J. J. Org. Chem. 2001, 66, 609.
    58. Barrett, A. G. M.; Cook, A. S.; Kamimura, A. Chem. Commun. 1998, 2533.
    59. Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.; Hatakeyama, S. J. Am. Chem. Soc. 1999, 121, 10219.
    60. Shi, M.; Chen, L.-H. Chem. Commun. 2003, 1310.
    61. Matsui, K.; Takizawa, S.; Sasai, H. J. Am. Chem. Soc. 2005, 127, 3680.
    62. Wang, J.; Li, H.; Yu, X.; Zu, L.; Wang, W. Org. Lett. 2005, 7, 4293.
    63. Bugarin, A.; Connell, B. T. Chem. Commun. 2010, 46, 2644.
    64. Song, H.-L.; Yuan, K.; Wu, X.-Y. Chem. Commun. 2011, 47, 1012.
    65. Rauhut, M. M.; Currier, H. (American Cyanamid Co.), U.S. Patent 307,499,919,630,122, 1963; Chem. Abstr. 1963, 58, 11224a.
    66. Morita, K.; Kobayashi, T. Bull. Chem. Soc. Jpn. 1969, 42, 2732.
    67. Wang, L.-C.; Luis, A. L.; Agapiou, K.; Jang, H.-Y.; Krische, M. J. J. Am. Chem. Soc. 2002, 124, 2402.
    68. Frank, S. A.; Mergott, D. J.; Roush, W. R. J. Am. Chem. Soc. 2002, 124, 2404.
    69. Aroyan, C. E.; Miller, S. J. J. Am. Chem. Soc. 2007, 129, 256.
    70. Dong, X.; Liang, L.; Li, E.; Hunag, Y. Angew. Chem. Int. Ed. 2015, 54, 1621.
    71. (a) Basavaiah, D.; Kumaragurubaran, N.; Sharada, D. S. Tetrahedron Lett. 2001, 42, 85.
    (b) Basavaiah, D.; Sharada, D. S.; Kumaragurubaran, N.; Reddy, R. M. J. Org. Chem. 2002, 67, 7135.
    72. Krafft, M. E.; Wright, J. A. Chem. Commun. 2006, 2977.
    73. Luis, A. L.; Krische, M. J. Synthesis 2004, 15, 2579.
    74. Jellerichs, B. G.; Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2003, 125, 7758.
    75. Krafft, M. E.; Seibert, K. A.; Haxell, T. F. N.; Hirosawa, C. Chem. Commun. 2005, 5772.
    76. For selected review articles on asymmetric organocatalytic domino reactions, see:
    (a) Enders, D.; Grondal, C.; Hüttl, M. R. M. Angew. Chem. Int. Ed. 2007, 46, 1570.
    (b) Volla, C. M. R.; Atodiresei, I.; Rueping, M. Chem. Rev. 2014, 114, 2390.
    77. Enders, D.; Hüttl, M. R. M.; Grondal, C.; Raabe, G. Nature 2006, 441, 861.
    78. Yetra, S. R.; Kaicharla, T.; Kunte, S. S.; Gonnade, R. G.; Biju, A. T. Org. Lett. 2013, 15, 5202.
    79. Takizawa, S.; Inoue, N.; Hirata, S.; Sasai, H. Angew. Chem. Int. Ed. 2010, 49, 9725.
    80. Shi, Z.; Yu, P.; Loh, T.-P.; Zhong, G. Angew. Chem. Int. Ed. 2012, 51, 7825.
    81. Rueping, M.; Volla, C. M. R. RSC Adv. 2011, 1, 79.
    82. Hoashi, Y.; Yabuta, T.; Takemoto, Y. Tetrahedron Lett. 2004, 45, 9185.
    83. Anwar, S.; Chang, H.-J.; Chen, K. Org. Lett. 2011, 13, 2200.
    84. Kuan, H.-H.; Chien, C.-H.; Chen, K. Org. Lett. 2013, 15, 2880.
    85. Anwar, S.; Li, S. M.; Chen, K. Org. Lett. 2014, 16, 2993.

    下載圖示
    QR CODE