藉由還原偶合反應 (Reductive Coupling Reaction；RCR) 來達成碳-碳鍵的生成，在有機合成的領域始終是不可或缺的工具。本實驗室多年來亦致力於此一領域；藉由催化量的鎳、鈷金屬錯合物以及劑量的鋅粉所架構出來的系統，可有效的應用在各種不同的π -component之間；達成一系列的還原偶合反應。
因此，本論文旨在延續實驗室之前的研究，對RCR做更深入的探討。發展了一系列新型態以及應用性廣泛的RCR。並分為三大部分來進行討論，包括 (1) 鎳金屬催化芳香亞胺與活化烯進行分子間RCR；(2)鋅粉-氨氣為媒介來進行“芳香羰基與活化烯類”，“缺電子酮基與活化炔類”與“鄰苯二甲醯亞胺與活化烯類”的分子間RCR；(3) 氨氣-鋅粉為媒介來進行sp2-碳-鹵鍵的嵌入，並對活化烯類進行分子間的共軛加成反應。
其中結合鋅粉與氨氣來進行分子間RCR，可經由：高位向選擇性、低成本、官能基忍度高、以及常溫常壓條件進行反應的方式，合成出具有生物活性的γ-hydroxybutyric acid前驅物、γ-內酯衍伸物、4-hydroxy -(E)-2-alkenoic esters與3-hydroxyisoindolin-1-one骨架分子。然而，針對氨氣活化鋅金屬進行RCR的反應機制而言仍屬未知，期望將來有一天可以進行更深入的研究，以得到更完善的了解。

The C-C bond construction via reductive coupling reaction (RCR) is a convenient tool for organic synthesis. In our lab, we have achieved various RCRs between different π-components which were based on catalytic amount of nickel/cobalt complex combined with stoichiometric amount of zinc as a system from several years ago.
In this thesis, we go further to explore different RCRs based on previous study and develop RCR with novel fashion to wide-broad application. Here, we discuss three types of RCR: (1) Nickel catalyzed intermolecular RCR of imines and activated alkenes. (2) Zinc-ammonia mediated various RCRs: “aryl carbonyls and activated alkenes”, “electron withdrawing ketones and activated alkenes”, “phthalimide and activated alkenes”. (3) Ammonia promoted zinc insertion of sp2-carbon halide bond: direct conjugate addition of functional aryl bromides with activated alkenes.
Especially, zinc ammonia mediated RCR which equips high regioselectivity, low cost, high tolerance of functional group, reaction proceeds under room temperature and atmospheric pressure. It’s a reliable way to synthesize a series of γ-hydroxybutyric acid precursors, γ-lactone derivatives, 4-hydroxy-(E)-2-alkenoic esters and 3-hydroxyisoindolin -1-one derivatives. However, the mechanism of zinc-ammonia mediated RCR is unclear for us to date. We wish to have further study and get the insight into interaction of zinc and ammonia in the future.

CH1
(1) Shono, T.; Kise, N.; Kunimi, N.; Nomura, R. Chem. Lett. 1991, 2191.
(2) (a) Takahashi, M.; Micalizio, G. C. J. Am. Chem. Soc. 2007, 129, 7514. (b) Takahashi, M.; Micalizio, G. C. Chem. Commun., 2010, 46, 3336.
(3) Kimura, M.; Miyachi, A.; Kojima, K.; Tanaka, S.; Tamaru, Y. J. Am. Chem. Soc. 2004, 126, 14360.
(4) (a) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Ind. Ed. 1998, 37, 1045. (b) Kürti, L.; Cakó, B. Strategic Applications of Named Reactions in Organic Synthesis; Elsevier Academic Press: Burlington, 2005; p 274.
(5) Moraoka, T.; Kamiya, S.; Matsuda, I.; Itoh, K. Chem. Commun. 2002, 1284.
(6) Garner, S. A.; Krische, M. J. J. Org. Chem., 2007, 72, 5843.
(7) Nishiyama, H.; Ishikawa, J.; Shiomi, T. Tetrahedron Lett. 2007, 48, 7841.
(8) Prieto, O.; Lam, H. W. Org. Biomol. Chem. 2008, 6, 55.
(9) The proposed mechanism based on: Lam, H. W.; Joensuu, P. M.; Murray, G. J.; Fordyce, E. A. F.; Prieto, O.; Luebbers, T. Org. Lett., 2006, 8, 3729.
(10) Du, Y.; Xu, W.; Shimizu, Y.; Oisaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2008, 130, 16146.
(11) (a) Shang, G.; Yang, Q.; Zhang, X. Angew. Chem. Int. Ed. 2006, 45, 6360. (b) Suzuki, A.; Mae, M.; Amii, H.; Uneyama, K. J. Org. Chem., 2004, 69, 5132.
(12) (a) Ogoshi, S.; Ikeda, H.; Kurosawa, H. Angew. Chem. Int. Ed. 2007, 46, 4930. (b) Chowdhury, S. K.; Amarasinghe, K. K. D.; Heeg, M. J.; Montgomery, J. J. Am. Chem. Soc. 2000, 122, 6775. (c) Amarasinghe, K. K. D.; Chowdhury, S. K.; Heeg, M. J.; Montgomery, J. Organometallics, 2001, 20, 370.
(13) Shang, G.; Yang, Q.; Zhang. X. Angew. Chem. Int. Ed. 2006, 45, 6360.
(14) Suzuki, A.; Mae, M.; Amii, H.; Uneyama. K. J. Org. Chem., 2004, 69, 5132.

CH2
(1) For relevant reviews, see: (a) Nishiyama, H.; Shiomi, T. Top. Curr. Chem. 2007, 279, 105. (b) Jang, H.-Y.; Krische, M. J. Acc. Chem. Res. 2004, 37, 653. (c) Huddleston, R. R.; Krische, M. J. Synlett 2003, 12. (d)
Chiu, P. Synthesis 2004, 2210. (e) Motherwell, W. B. Pure Appl. Chem. 2002, 74, 135.
(2) Nishiyama, H.; Shiomi, T. Top. Curr. Chem. 2007, 279, 105.
(3) Revis, A.; Hilty, T. K. Tetrahedron Lett. 1987, 28, 4809.
(4) (a) Namy, J. L.; Girard, P.; Kagan, H. B. New J. Chem. 1977, 1, 5. (b) Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102, 2693.
(5) Nicolaou, K. C.; Ellery, S. P.; Chen, J. S. Angew. Chem. Int. Ed. 2009, 48, 7140.
(6) Fukuzawa, S.-i.; Nakanishi, A.; Fujinami, T.; Sakai, S. J. Chem. Soc. Chem. Commun. 1986, 624.
(7) Otsubo, K.; Inanaga, J.; Yamaguchi, M. Tetrahedron Lett. 1986, 27, 5763.
(8) Kawatsura, M.; Matsuda, F.; Shirahama, H. J. Org. Chem., 1994, 59, 6900.
(9) Fukuzawa, S.; Seki, K.; Tatsuzawa, M.; Mutoh, K. J. Am. Chem. Soc. 1997, 119, 1482.
(10) Kimura, M.; Ezoe, A.; Mori, M.; Iwata, K.; Tamaru, Y. J. Am. Chem. Soc. 2006, 128, 8559.
(11) Kimura, M.; Ezoe, A.; Shibata, K.; Tamaru, Y. J. Am. Chem. Soc. 1998, 120, 4033.
(12) Yang, Y.; Zhu, S.-F.; Duan, H.-F.; Zhou, C.-Y.; Wang, L.-X.; Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129, 2248.
(13) Shono, T.; Ohmizu, H.; Kawakami, S.; Sugiyama, H. Tetrahedron Lett. 1980, 21, 5029.
(14) Shono, T.; Hamaguchi, H.; Nishiguchi, I.; Sasaki, M.; Miyamoto, T.; Miyamoto, M.; Fujita, S. Chem. Lett. 1981, 1217.

CH3
(1) Oblinger, E.; Montgomery, J. J. Am. Chem. Soc. 1997, 119, 9065.
(2) Huang, W.S.; Chan, J.; Jamison, T.F. Org. Lett. 2000, 2, 4221.
(3) (a) Colby, E. A.; Jamison, T. F. J. Org. Chem. 2003, 68, 156. (b) Miller, K. M.; Huang, W. S.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 3442. (c) Miller, K. M.; Molinaro, C.; Jamison, T. F. Tetrahedron: Asymmetry 2003, 14, 3619. (d) Takai, K.; Sakamoto, S.; Isshiki, T. Org. Lett. 2003, 5, 653. (e) Luanphaisarnnont, T.; Ndubaku, C. O.; Jamison, T. F. Org. Lett. 2005, 7, 2937. (f) Moslin, R. M.; Miller, K. M.; Jamison, T. F. Tetrahedron 2006, 62, 7598. (g) Moslin, R. M.; Jamison, T. F. Org. Lett. 2006, 8, 455. (h) Sa-Ei, K.; Montgomery, J. Org. Lett. 2006, 8, 4441. (i) Chaulagain, M. R.; Sormunen, G. J.; Montgomery, J. J. Am. Chem. Soc. 2007, 129, 9568. (j) Yang, Y.; Zhu, S.-F.; Zhou, C.-Y.; Zhou, Q.-L. J. Am. Chem. Soc. 2008, 130, 14052. (k) Saito, N.; Katayama, T.; Sato, Y. Org. Lett. 2008, 10, 3829. (l) Trenkle, J. D.; Jamison, T. F. Angew.
Chem., Int. Ed. 2009, 48, 5366. (m) Malik, H. A.; Chaulagain, M. R.; Montgomery, J. Org. Lett. 2009, 11, 5734.
(4) Komanduri, V.; Krische, M.J. J. Am. Chem. Soc. 2006, 128, 16448.
(5) Inanaga, J.; Katsuki, J.; Ujikawa, O.; Yamaguchi, M. Tetrahedron Lett. 1991, 32, 4921.
(6) Kwon, D. W.; Cho, M. S.; Kim, Y. H. Synlett. 2001, 627.
(7) Oka, R.; Nakayama, M.; Sakaguchi, S.; Ishii, Y. Chem. Lett. 2006, 35, 1104.
(8) Geraghty, N. W. A.; Hernon, E. M. Tetrahedron Lett. 2009, 50, 570.
(9) Van Haard, P. M. M.; Thijs, L.; Zwanenburg, B. Tetrahedron Lett. 1975, 803.
(10) Arcadi, A.; Cacchi, S.; Carelli, I.; Curulli, A.; Inesi, A.; Marinelli, F.; Synlett 1990, 408.
(11) R. Tanikaga, Y. Nozaki, K. Tanaka, A. Kaji, Chem. Lett. 1982, 11, 1703.

CH4
(1) Vacas, T.; Alvarez, E.; Chiara, J. L. Org. Lett. 2007, 9, 5445.
(2) Kise, N.; Isemoto, S.; Sakurai, T. Org. Lett. 2009, 11, 4902.
(3) Shono,T.; Ohmizu, H.; Kawakami, S.; Sugiyama, H. Tetrahedron Lett. 1980, 21, 5029.
(4) (a) McDermott, G.; Yoo, D. J.; Oelgemoller, M. Heterocycles 2005, 65, 2221. (b) Oelgemoller, M.; Griesbeck, A. G. In CRC Handbook of Organic Photochemistry and Photobiology; Horspool, W. M., Lenci, F., Eds., 2nd ed.; CRC Press: Boca Raton, 2004; pp 1–19. Chapter 84. (c) Oelgemoller, M.; Griesbeck, A. G. J. Photochem. Photobiol., C: Photochem. Rev. 2002, 3, 109. (d) Yoon, U. C.; Mariano, P. S. Acc. Chem. Res. 2001, 34, 523. (e) Coyle, J. D. In Synthetic Organic Photochemistry; Horspool, W. M., Ed.; Plenum Press: New York, 1984; pp 259–284. (f) Mazzocchi, P. H. Org. Photochem. 1981, 5, 421. (g) Kanaoka, Y. Acc. Chem. Res. 1978, 11, 407.
(5) Gallagher, S.; Hatoum, F.; Zientek, N.; OelgemÖller, M. Tetrahedron Lett. 2010, 51, 3639.
(6) Neumann, H.; StrMbing, D.; Lalk, M.; Klaus, S.; HMbner, S.; Spannenberg, A.; Lindequist, U.; Beller, M.; Org. Biomol. Chem. 2006, 4, 1365.
(7) Bootwicha, T.; Kuhakarn, C.; Prabpai, S.; Kongsaeree, P.; Tuchinda, P.; Reutrakul, V.; Pohmakotr, M. J. Org. Chem., 2009, 74, 3798.
(8) Zhou, Y.; Zhai, Y.; Li, J.; Ye, D.; Jiang, H.; Liu, H. Green Chem. 2010, 12, 1397.
(9) Hardcastle, I. R.; Ahmed, S. U.; Atkins, H.; Farnie, G.; Golding, B. T.; Griffin, R. J.; Guyenne, S.; Hutton, C.; Kallblad, P.; Kemp, S. J.; Kitching, M. S.; Newell, D. R.; Norbedo, S.; Northen, J. S.; Reid, R. J.; Saravanan, K.; Willems, H. M. G.; Lunec, J. J. Med. Chem. 2006, 49, 6209.
(10) Chen, M.-D.; Zhou, X.; He, M.-Z.; Ruan, Y.-P.; Huang, P.-Q. Tetrahedron 2004, 60, 1651.
(11) Vasilevskaya, T. N.; Yakovleva, O. D.; Kobrin, V. S. Synth. Commun. 1995, 25, 2463.
(12) Chiurato, M.; Routier, S.; Troin, Y.; Guillaumet, G. E. J. Org. Chem. 2009, 3011.
(13) Barn, D.R. ; Caulfield, W.L.; Cottney, J.; McGurk, K.; Morphy, J.R.; Rankovica, Z.; Roberts, B. Bioorg. Med. Chem 2001, 9, 2609.
(14) Zhang, J.; Xiong, C.; Ying, J.; Wang, W.; Hruby, V. J. Org. Lett. 2003, 5, 3115.
(15) Little T. L.; Webber, S. E. J. Org. Chem. 1994, 59, 7299.
(16) Bull, S. D.; Davies, S. G.; Kelly, P. M.; Gianotti , M.; Smith, A. D. J. Chem. Soc., Perkin Trans. 1, 2001, 3106.

CH5
(1) Blanchard, P.; Da Silva, A. D.; El Kortbi, M. S.; Fourrey, J.-L.; Machado, A. S.; Robert-Gero, M. J. Org. Chem. 1993, 58, 6517.
(2) J. Perez Sestelo, J. L, Mascarenas, L. Castedo, A. Mourino, J. Org. Chem. 1993, 58, 118.
(3) Manchand, P. S.; Yiannikouros, G. P.; Belica, P. S.; Madan, P. J. Org. Chem. 1995, 60, 6574.
(4) (a) Petrier, C.; Dupuy, C.; Luche, J. L. Tetrahedron Lett. 1986, 27, 3149. (b) Luche, J. L.; Allavena, C.; Tetrahedron Lett. 1988, 29, 5369. (c) Dupuy, C.; Petrier, C.; Sarandeses, L. A.; Luche, J. L.; Synth. Commun. 1991, 21, 643. (d) Sarandeses, L. A.; Mourino, A.; Luche, J. L.; J. Chem. Soc. Chem. Commun. 1992, 798. (e) Perez Sestelo, J.; Cornella, I.; de Una, O.; Mourino, A.; Sarandeses, L. A. Chem. Eur. J., 2002, 8, 2747 (f) Suarez, R. M.; Perez Sestelo, J.; Sarandeses, L. A. Chem. Eur. J. 2003, 9, 4179. (g) Suarez, R. M.; Perez Sestelo, J.; Sarandeses, L. A. Org. Biomol. Chem. 2004, 2, 3584. (h) Fleming, F. F.; Gudipati, S. Org. Lett. 2006, 8, 1557.
(5) (a) Woodward, S. Chem. Soc. Rev. 2000, 29, 393. (b) Jerphagnon, T.; Pizzuti, M. G.; Minnaard, A. J.; Feringa, B. L. Chem. Soc. Rev. 2009, 38, 1039. (c) The Chemistry of Organozinc Compounds, John Wiley & Sons: Chichester, UK, 2006
(6) Cahiez, G.; Venegas, P.; Tucker, C. E.; Maid, T. N.; Knochel, P. J. Chem. Soc., Chem. Commun. 1992, 1406.
(7) Berger, S.; Langer, F.; Lutz, C.; Knochel, P.; Mobley, T. A.; Reddy, C. K. Angew. Chem., Int. Ed. 1997, 36, 1496.
(8) Jones, P.; Reddy, C. K.; Knochel, P. Tetrahedron 1998, 54, 1471.
(9) Condon, S.; Léonel, E.; Nédélec, J. Y.; Périchon, J. J. Org. Chem. 1995, 60, 7684.
(10) Condon, S.; Dupré, D.; Falgayrac, G.; Nédélec, J.-Y. Eur. J. Org. Chem. 2002, 105.
(11) Gomes, P.; Gosmini, C.; Nédélec, J. Y.; Périchon, J. Tetrahedron Lett. 2000, 41, 3385.
(12) Gomes, P.; Gosmini, C.; Périchon, J. Synlett 2002, 1673.
(13) Lebedev, S.A.; Lopatina,V. S.; Petrov,E. S.;Beletskaya, I. P. J. Organomet. Chem. 1988, 344, 253.
(14) Sustmann, R.; Hopp, P.; Holl, P. Tetrahedron Lett. 1989, 30, 689.
(15) Sim, T. B.; Choi, J.; Yoon, N. M. Tetrahedron Lett. 1996, 37, 3137.
(16) Varchi, G.; Ricci, A.; Cahiez, G.; Knochel, P. Tetrahedron 2000, 56, 2727.
(17) Shukla, P.; Hsu, Y.-C.; Cheng, C.-H. J. Org. Chem. 2006, 71, 655.
(18) Amatore, M.; Gosmini, C.; Péichon, J. J. Org. Chem. 2006, 71, 6130.