本篇論文主要研究，利用不同的金雞鈉鹼衍生的催化劑進行有機不對稱的催化反應來建構具有高鏡像選擇性的螺環產物。
第一部分，設計可在反應中同時扮演親核性試劑與親電子性試劑的香豆素衍生物31，與1,3-茚二酮烯類衍生物30進行協同反應 (concerted) 及逐步反應 (stepwise) 行 [3+2] 反應合環，建構單一非鏡像異構物、高鏡像選擇性且具有四個掌性中心的螺環骨架化合物，並利用各種控制實驗，觀察到逆反應的存在以及鏡像超越值的變化，藉此推導其可能的反應機構。
第二部分，以1,3-茚二酮烯類衍生物 30 與 ,-不飽合酮類 39 進行有機不對稱共價催化反應，建構具有高非鏡像與高鏡像選擇性的螺環骨架的環己酮衍生物 40，且其種一個在環己酮環上 位加成官能基的反式純鏡像螺環骨架衍生物可以差向異構形成熱力學穩定的順式產物，只有些微降低鏡像選擇性，藉此證明了本文所推導的反應機構。
反應機構會經由兩種互相競爭的反應路徑，一個是Diels−Alder反應，另一個是逐步的Michael加成，藉此形成所對應的產物。

In my thiesis, the cinchona alkaloid derived organocatalysts were utilized for the synthesis of cyclohexanone and cyclopentanone derivatives via the covalent or non-covalent asymmetric organocatalysis.

In the first part, a new class of coumarin derivatives, bearing an electrophilic and a nucleophilic site at the same time, have been developed. Cinchona alkaloid-derived chiral hydrogen bonding catalysts were utilized to carry out the [3+2] cyclization of these coumarin derivatives with 2-alkylidene indandiones. The corresponding spiro products bearing four stereocenters, including an all-carbon quaternary center, were obtained as single diastereomers with high enantioselectivity. The Michael addition intermediate was also isolated and a few control experiments have been performed to support the proposed mechanism.

In second part, a cinchona-alkaloid derived chiral primary-amine-catalyzed enantioselective spirocyclohexanones derivatives is demonstrated. Both the enantiomeric forms of the trans isomer are obtained in excellent yields and enantioselectivities. Mechanistic investigations revealed two competing pathways, a concerted Diels−Alder reaction and a stepwise Michael addition, for the formation of corresponding products.

第一部分

1. a) R. D. H. Murray, J. Mendez, R. A. Brown, The Natural Coumarins, John Wiley & Sons, New York, 1982. b) Coumarins: Biology, Applications and Mode of Action, (Eds.: R. O Kennedy, R. D. Thornes), Wiley, New York, 1997. c) J. R. S. Hoult, M. Paya, Gen. Pharmacol. 1996, 27, 713. d) K. C. Fylaktakidou, D. J. Hadjipavlou-Litina, K. E. Litinas, D. N. Nicolaides, Curr. Pharm. Des. 2004, 10, 3813. e) J. Widelski, E. Melliou, N. Fokialakis, P. Magiatis, K. Glowniak, I. Chinou, J. Nat. Prod. 2005, 68, 1637.
2. a) L. Xie, Y. Takeuchi, L. M. Cosentino, K. H. Lee, J. Med. Chem. 1999, 42, 2662. b) T. Ishikawa, Heterocycles 2000, 53, 453. c) . Xie, Y. Takeuchi, L. M. Cosentino, A. T. McPhail, K. H. Lee, J. Med. Chem. 2001, 44, 664. d) G. Cravotto, G. M. Nano, G. Palmisano, S. Tagliapietra, Tetrahedron: Asymmetry 2001, 12, 707. e) M. Ufer, Clin. Pharmacokinet. 2005, 44, 1227. f) L. E. Visser, R. H. van Schaik, M. van Vliet, P. H. Trienekens, P. A. De Smet, A. G. Vulto, A. Hofman, C. M. van Duijn, B. H. Stricker, Clin. Pharmacol. Ther. 2005, 77, 479. g) X. Cao, W. Lin, Q. Yu, J. Wang, Org. Lett. 2011, 13, 6098. h) M. G. Choi, J. Hwang, J. O. Moon, J. Sung, S.-K. Chang, Org. Lett. 2011, 13, 5260.
3. For general reviews on asymmetric organocatalysis, see: a) Enantioselective Organocatalysis, (Ed.: P. I. Dalko), Wiley-VCH, Weinheim, 2007. b) D. W. C. MacMillan, Nature 2008, 455, 304. c) E. N. Jacobsen, D. W. C. MacMillan, Proc. Natl. Acad. Sci. USA 2010, 107, 20618.
4. For reviews on aminocatalysis, see: a) G. Lelais, D. W. C. MacMillan, Aldrichimica Acta 2006, 39, 79. b) S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471. c) P. Melchiorre, M. Marigo, A. Carlone, G. Bartoli, Angew. Chem. Int. Ed. 2008, 47, 6138 d) S. Bertelsen, K. A. Jorgensen, Chem. Commun. 2009, 2178 e) M. Nielsen, D. Worgull, T. Zweifel, B. Gschwend, S. Bertelsen, K. A. Jørgensen, Chem. Commun. 2011, 47, 632.
5. For selected recent reviews on H-bond catalysis, see: a) S. J. Connon, Chem. Commun. 2008, 2499. b) Y. Takemoto, Chem. Pharm. Bull. 2010, 58, 593. c) W.-Y. Siau, J. Wang, Catal. Sci. Technol. 2011, 1, 1298. d) L.-Q. Lu, X.-L. An, J.-R. Chen, W.-J. Xiao, Synlett 2012, 490; for a review on iminium ion catalysis, see: e) A. Erkkila, I. Majander, P. M. Pihko, Chem. Rev. 2007, 107, 5416.
6. a) N. Halland, T. Hansen, K. A. Jørgensen, Angew. Chem. Int. Ed. 2003, 42, 4955. b) H. Kim, C. Yen, P. Preston, J. Chin, Org. Lett. 2006, 8, 5239. c) J.-W. Xie, L. Yue, W. Chen, W. Du, J. Zhu, J.-G. Deng, Y.-C. Chen, Org. Lett. 2007, 9, 413. d) T. E. Kristensen, K. Vestli, F. K. Hansen, T. Hansen, Eur. J. Org. Chem. 2009, 5185. e) X.-K. Chen, C.-W. Zheng, S.-L. Zhao, Z. Chai, Y.-Q. Yang, G. Zhao, W.-G. Cao, Adv. Synth. Catal. 2010, 352, 1648. f) D.-Q. Xu, Y.-F. Wang, W. Zhang, S. P. Luo, A.-G. Zhong, A. B. Xia, Z.-Y. Xu, Chem. Eur. J. 2010, 16, 4177. g) Y. Gao, Q. Ren, L. Wang, J. Wang, Chem. Eur. J. 2010, 16, 13068. h) X. Zhu, A. Lin, Y. Shi, J. Guo, C. Zhu, Y. Cheng, Org. Lett. 2011, 13, 4382. i) R. Q. Mei, X. Y. Xu, Y.-C. Li, J.-Y. Fu, Q.-C. Huang, L.-X. Wang, Tetrahedron Lett. 2011, 52, 1566. j) M. Rogozińska, A. Adamkiewicz, J. Mlynarski, Green Chem. 2011, 13, 1155. k) J. Dong, D. M. Du, Org. Biomol. Chem. 2012, 10, 8125. l) M. Leven, J. M. Neudörfl, B. Goldfuss, Beilstein J. Org. Chem. 2013, 9, 155.
7. Y.-T. Lee, U. Das, Y.-R. Chen, C.-J. Lee, C.-H. Chen, M.-C. Yang, W. Lin, Adv. Synth. Catal. 2013, 355, 3154.
8. I. R. Pottie, P. R. Nandaluru, W. L. Benoit, D. O. Miller, L. N. Dawe, G. J. Bodwell, J. Org. Chem. 2011, 76, 9015.
9. a) B. L. Feringa, Acc. Chem. Res. 2000, 33, 346. b) A. W. Hird, A. H. Hoveyda, J. Am. Chem. Soc. 2005, 127, 14988. c) M. d’Augustin, L. Palais, A. Alexakis, Angew. Chem. Int. Ed. 2005, 44, 1376 d) R. Shintani, Y. Tsutsumi, M. Nagaosa, T. Nishimura, T. Hayashi, J. Am. Chem. Soc. 2009, 131, 13588. e) Y. Tanaka, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2010, 132, 8862. f) C. Mazet, E. N. Jacobsen, Angew. Chem. Int. Ed. 2008, 47, 1762. g) X. Feng, J. Yun, Chem. Eur. J. 2010, 16, 13609. h) D. Zhao, L. Mao, L. Wang, D. Yang, R. Wang, Chem. Commun. 2012, 48, 889. i) K. Kikushima, J. C. Holder, M. Gatti, B. M. Stoltz, J. Am. Chem. Soc. 2011, 133, 6902.
10. a) M. D. Pierce, R. C. Johnston, S. Mahapatra, H. Yang, R. G. Carter, P. H.-Y. Cheong, J. Am. Chem. Soc. 2012, 134, 13624. b) L.-Y. Wu, G. Bencivenni, M. Mancinelli, A. Mazzanti, G. Bartoli, P. Melchiorre, Angew. Chem. Int. Ed. 2009, 48, 7196. c) G. Bencivenni, L.-Y. Wu, A. Mazzanti, B. Giannichi, F. Pesciaioli, M.-P. Song, G. Bartoli, P. Melchiorre, Angew. Chem. Int. Ed. 2009, 48, 7200.
11. D. Bastida, Y. Liu, X. Tian, E. Escudero-Adan, and P. Melchiorre, Org. Lett., 2013, 15, 220.
12. D. Yang, L. Wang, F. Han, D. Zhao, B. Zhang, and R. Wang, Angew. Chem., Int. Ed. 2013, 52, 6739.
13. L. Möhlmann, G.-H. Chang, G. M. Reddy, C.-J. Lee, and W. Lin, Org. Lett., 2016, 18, 688.

第二部分

1. For reviews on non-cinchona alkaloid derived chiral primary amine based organocatalysis, see (a) F. Peng, Z. J. Shao, Molecular Catalysis A: Chemical 2008, 285, 1. (b) L.-W. Xu, J. Luo, Y. Lu, Chem. Commun. 2009, 1807. (c) O. V. Serdyuk, C. M. Heckel, S. B. Tsogoeva, Org. Biomol. Chem. 2013, 11, 7051. (d) L. Zhang, S. Luo, Synlett, 2012, 1575. (e) Z. Chai, G. Zhao, Catal. Sci. Technol. 2012, 2, 29.
2. (a) U. Scheffler, R. Mahrwald, Synlett 2011, 1660. (b) B. List, Tetrahedron 2002, 58, 5573. (c) K. L. Jensen, G. Dickmeiss, H. Jiang, L. Albrecht, K. A. Jørgensen, Acc. Chem. Res. 2012, 45, 248. d) S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471.
3. (a) G. Lelais, D. W. C. MacMillan, Aldrichimica Acta 2006, 39, 79-87. (b) M. M. Heravi, V. Zadsirjan, Tetrahedron: Asymmetry 2013, 24, 1149.
4. For representative reviews on cinchona alkaloid derived primary amine catalysis, see: (a) P. Melchiorre, Angew. Chem. Int. Ed. 2012, 51, 9748. (b) J. Duan, P. Li, Catal. Sci. Technol. 2014, 4, 311. (c) L. Jiang, Y.-C. Chen, Catal. Sci. Technol. 2011, 1, 354. (d) Y.-C. Chen, Synlett, 2008, 12, 1919. (e) G. Bartoli, P. Melchiorre, Synlett, 2008, 12, 1759.
5. L.-Y. Wu, G. Bencivenni, A. Mazzanti, G. Bartoli, P. Melchiorre, Angew. Chem. Int. Ed. 2009, 48, 7196.
6. R. Thayumanavan, B. Dhevalapally, K. Sakthivel, F. Tanaka, C. F. Barbas III, Tetrahedron Lett. 2002, 43, 3817.
7. For an outlook on our group’s efforts towards developing cinchona alkaloid-derived primary amine catalysis, see (a) U. Das, C.-H. Huang, W. Lin, Chem. Commun. 2012, 48, 5590. (b) Y.-T. Lee; U. Das, Y.-R. Chen, C.-J. Lee, C.-H. Chen, M.-C. Yang, W. Lin, Adv. Synth. Catal. 2013, 355, 3154.
8. (a) D. B. Ramachary, K. Anebouselvy, N. S. Chowdari, C. F. Barbas III, J. Org. Chem. 2004, 69, 5838. (b) D. B. Ramachary, N. S. Chowdari, C. F. Barbas III, Synlett. 2003, 1910.
9. N.-H. Luo, X. Sun, W.-T. Wei, X.-J. Zhang, M. Yan, Tetrahedron: Asymmetry 2013, 24, 402.
10. S. Anwar, S. M. Li, K. Chen, Org. Lett. 2014, 16, 2993.
11. H.-H. Kuan, C.-H. Chien, K. Chen, Org. Lett. 2013, 15, 2880.
12. D. B. Ramachary, C. Venkaiah, P. M. Krishna, Chem. Commun. 2012, 48, 2252.
13. B. Bredenkotter, B. Neumann, H.-G. Stammler, D. Kuck, Eur. J. Org. Chem. 2014, 53.
14. P. S. Silaichev, V. O. Filimonov, P. A. Slepukhin, M. Rubin, A. N. Maslivets, Eur. J. Org. Chem. 2015, 2739.
15. W. Hoeve, H. Wynberg, J. Org. Chem. 1979, 44, 1508.
16. D. Pizzirani, M. Roberti, M. Recanatini, Tetrahedron Lett. 2007, 48, 7120.
17. (a) J. Shi, Y. Liu, M. Wang, L. Lin, X. Liu, X. Feng, Tetrahedron 2011, 67, 1781. (b) D. B. Ramachary, N. S. Chowdari, C. F. Barbas III, Angew. Chem. Int. Ed.. 2003, 42, 4233. (c) G. Bencivenni, L.-Y. Wu, A. Mazzanti, B. Giannichi, F. Pesciaioli, M.-P. Song, G. Bartoli. P. Melchiorre, Angew. Chem. Int. Ed. 2009, 48, 7200. (d) D. Cheng, Y. Ishihara, B. Tan, C. F. Barbas III, ACS Catal. 2014, 4, 743. (e) D. B. Ramachary, C. F. Barbas III, Org. Lett. 2005, 7, 1577.
18. D. Pizzirani, M. Roberti, S. Grimaudo, A. D. Cristina, R. M. Pipitone, M. Tolomeo, M. Recanatini, J. Med. Chem. 2009, 52, 6936.
19. The absolute configurations of trans-40ca, trans-57cca and cis-71ca, cis-72aca were established by X-ray crystallography.
20. A. T. Rowland, S. A. Filla, M. L. Coutlangus, M. D. Winemiller, M. J. Chamberlin, G. Czulada, S. D. Johnson, J. Org. Chem. 1998, 63, 4359.