烯炔複分解反應是藉由釕金屬去對於烯類與炔類進行複分解反應，已被用於一些小分子的合環反應中，而可能會有許多因素影響其反應性，像是本身其立體障礙、官能基、分子內雜原子和所利用的催化劑等。已有研究報導含有烯丙基位氧族元素(氧、硫、硒)的分子在水相進行烯烴複分解反應有著顯著提升速率的效果。本論文針對烯丙基位氧族元素的取代對其烯炔複分解反應的速率的影響及其應用於環胜肽的合成進行測試。本論文選擇的是丙炔基位硫化物小分子，催化劑方面則是選擇與硫化物最適合且可以用於水相中的Hoveyda-Grubbs 二代催化劑，發現在大量烯反應物的條件下可使反應進行，但並無明顯提升效果且產率低，而後延伸此合成方法用於環胜肽的合環反應中，可能因為立障或環張力導致無反應或者形成烯類端自身交叉複分解之產物。雖然此特性應用於烯炔複分解反應中並無特別成效，對此初步結果仍可持續探討並更進一步的改善與應用。

Enyne metathesis is a metathesis reaction between an alkyne and an alkene in the presence of metal carbene catalyst forming a conjugate diene as the product. It has been used in synthesis of small cyclic molecule via ring-closing metathesis. There are many factors that affect its reactivity. For example, steric hindrance, functional groups, heteroatom in molecule, and the type of catalyst used. It has been reported that the rate of olefin metathesis of molecules containing allyl chalcogen (O, S, Se) in the aqueous solution has a significant enhancement in rate. In this thesis, the allylic chalcogen effect in enyne metathesis and application towards bicyclic peptide synthesis is explored. Small molecules containing propargyl sulfide were chosen and Hoveyda Grubbs 2nd generation catalyst having the highest tolerance for sulfur atom was used. Large quivalence of alkenes was found to be essential for intermolecular enyne cross metathesis to work, although the reaction can be work, but no significant enhancement observed and the yield is low. Next, this method was extended to the synthesis of cyclic peptides by ring-closing enyne metathesis to see check the application of intramolecular reaction. Disappointingly, no desired product could be obtained and large amount of starting material remained in reaction mixture. Although the effect of chalcogen groups in enyne metathesis is not particularly effective, we still retain a high degree of interest and hope to improve this reaction futher for other application in synthesis.

論文審定書 i
論文公開授權書 ii
誌謝 iii
中文摘要 iv
Abstract v
目次 vi
圖目錄 viii
流程目錄 x
表目錄 xi
光譜目錄 xii
縮寫表 xiv
第一章緒論 1
第一節 研究背景 1
1.1.1 烯烴複分解反應簡介 1
1.1.2 烯炔複分解反應簡介 2
1.1.3 烯炔複分解反應機制簡介 3
1.1.4 烯炔複分解反應應用 4
第二節. 烯烴複分解化反應於擬肽物的應用 6
1.2.1 擬肽物簡介 6
1.2.2 利用RCM反應去合成β-Turn的胜肽 7
1.2.3 利用RCM去合成螺旋狀間的鍵結 7
1.2.4 利用RCM反應去合成二碳類似物 8
第三節 水相烯烴複分解反應 9
1.3.1 早期 9
1.3.2 勻相水溶液中進行烯烴複分解反應 10
1.3.3 純水相中進行烯烴複分解反應 11
1.3.4 加入介面活性劑幫助水相烯烴複分解反應 12
1.3.5 水相催化劑的發展 13
第四節 烯丙基位氧族原子對烯烴複分解反應的影響 14
1.4.1 烯丙基位氫氧根對烯烴複分解反應的影響 14
1.4.2 烯丙基位上氧族元素對烯烴複分解反應的影響 15
第二章 研究動機 18
第三章 實驗結果與討論 19
第四章 引用文獻 33
第五章 實驗步驟與光譜數據 36
第一節 儀器設備與藥品材料 36
第二節 合成步驟與光譜數據 38
第六章、光譜資料 64

(1) Katz, T. J.; Lee, S. J. J. Am. Chem. Soc. 1980, 102, 422.
(2) Katz, T. J.; Ho, T. H.; Shih, N. Y.; Ying, Y. C.; Stuart, V. I. W. J. Am. Chem. Soc. 1984, 106, 2659.
(3) Landon, S. J.; Shulman, P. M.; Geoffroy, G. L. J. Am. Chem. Soc. 1985, 107, 6739.
(4) Schuehler, D. E.; Williams, J. E.; Sponsler, M. B. Macromolecules 2004, 37, 6255.
(5) Katsumata, T.; Shiotsuki, M.; Sanda, F.; Sauvage, X.; Delaude, L.; Masuda, T. Macromol. Chem. Phys. 2009, 210, 1891.
(6) Santhosh Kumar, P.; Wurst, K.; Buchmeiser, M. R. J. Am. Chem. Soc. 2009, 131, 387.
(7) Peters, J. U.; Blechert, S. Chem. Commun. 1997, 1983.
(8) Das, S. K.; Roy, R. Tetrahedron Lett. 1999, 40, 4015.
(9) Witulski, B.; Stengel, T.; Fernández-Hernández, J. M. Chem. Commun. 2000, 1965.
(10) Katz, T. J.; Sivavec, T. M. J. Am. Chem. Soc. 1985, 107, 737.
(11) Watanuki, S.; Ochifuji, N.; Mori, M. Organometallics 1994, 13, 4129.
(12) Watanuki, S.; Ochifuji, N.; Mori, M. Organometallics 1995, 14, 5062.
(13) Lippstreu, J. J.; Straub, B. F. J. Am. Chem. Soc. 2005, 127, 7444.
(14) Kaliappan, K. P.; Subrahmanyam, A. V. Org. Lett. 2007, 9, 1121.
(15) Kotha, S.; Meshram, M.; Tiwari. J. A. Chem. Soc. Rev. 2009, 38, 2065.
(16) Schürer, S. C.; Blechert, S. Tetrahedron Lett. 1999, 40, 1877.
(17) Stragies, R.; Voigtmann, U.; Blechert, S. Tetrahedron Lett. 2000, 41, 5465.
(18) Giessert, A. J.; Snyder, L.; Markham, J.; Diver, S. T. Org. Lett. 2003, 5, 1793.
(19) Kim, M.; Park, S.; Maifeld, S. V.; Lee, D. J. Am. Chem. Soc. 2004, 126, 10242.
(20) Galan, B. R.; Giessert, A. J.; Keister, J. B.; Diver, S. T. J. Am. Chem. Soc. 2005, 127, 5762.
(21) Park, S.; Kim, M.; Lee, D. J. Am. Chem. Soc. 2005, 127, 9410.
(22) Clark, D. A.; Basile, B. S.; Karnofel, W. S.; Diver, S. T. Org. Lett. 2008, 10, 4927.
(23) Diver, S. T.; Clark, D. A.; Kulkarni, A. A. Tetrahedron 2008, 64, 6909.
(24) Giessert, A. J.; Brazis, N. J.; Diver, S. T. Org. Lett. 2003, 5, 3819.
(25) Fink, B. E.; Kym, P. R.; Katzenellenbogen. J. Am. Chem. Soc.1998, 120, 4334.
(26) Patgiri, A.; Jochim, A. L.; Arora, P. S. Acc. Chem. Res. 2008, 41, 1289.
(27) Stymiest, J. L.; Mitchell, B. F.; Wong, S.; Vederas, J. C. Org. Letters. 2003, 5, 47.
(28) Blackwell, H. E.; O'Leary, D. J.; Chatterjee, A. K.; Washenfelder, R. A.; Bussmann, D. A.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 58.
(29) Hillmyer, M. A.; Lepetit, C.; McGrath, D. V.; Novak, B. M.; Grubbs, R. H. Macromolecules 1992, 25, 3345.
(30) Mortell, K. H.; Weatherman, R. V.; Kiessling, L. L. J. Am. Chem. Soc.1996, 118, 2297.
(31) Novak, B. M.; Grubbs, R. H. J. Am. Chem. Soc.1988, 110, 7542.
(32) Binder, J. B.; Blank, J. J.; Raines, R. T. Org. Letters. 2007, 9, 4885.
(33) Conrad, J. C.; Eelman, M. D.; Silva, J. A. D.; Monfette, S.; Parnas, H. H.; Snelgrove, J. L.; Fogg, D. E. J. Am. Chem. Soc.2007, 129, 1024.
(34) Fürstner, A.; Langemann, K. The Journal of Organic Chemistry 1996, 61, 3942.
(35) Blackmond, D. G.; Armstrong, A.; Coombe, V.; Wells, A. Angew. Chem. 2007, 119, 3872.
(36) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.; Sharpless, K. B. Angew. Chem. 2005, 117, 3339.
(37) Hayashi, Y. Angew. Chem. 2006, 118, 8281.
(38) Lynn, D. M.; Kanaoka, S.; Grubbs, R. H. J. Am. Chem. Soc.1996, 118, 784.
(39) Lipshutz, B. H.; Aguinaldo, G. T.; Ghorai, S.; Voigtritter, K. Org. Lett. 2008, 10, 1325.
(40) Lipshutz, B. H.; Ghorai, S.; Aguinaldo, G. T. Advanced Synthesis & Catalysis 2008, 350, 953.
(41) Grubbs, R. H. In Aqueous Organometallic Chemistry and Catalysis; Horváth, I. T., Joó, F., Eds.; Springer Netherlands: Dordrecht, 1995, p 15.
(42) Dowden, J.; Savovic, J. Chemical Communications 2001, 37.
(43) Connon, S. J.; Blechert, S. Bioorganic & Medicinal Chemistry Letters 2002, 12, 1873.
(44) Hoye, T. R.; Zhao, H. Org. Lett.1999, 1, 1123.
(45) Nicolaou, K. C.; Leung, G. Y. C.; Dethe, D. H.; Guduru, R.; Sun, Y.-P.; Lim, C. S.; Chen, D. Y. K. J. Am. Chem. Soc. 2008, 130, 10019.
(46) Lin, Y. A.; Chalker, J. M.; Floyd, N.; Bernardes, G. J. L.; Davis, B. G. J. Am. Chem. Soc.2008, 130, 9642.
(47) Lin, Y. A.; Chalker, J. M.; Davis, B. G. J. Am. Chem. Soc.2010, 132, 16805.
(48) Marshall, J. E.; Keister, J. B.; Diver, S. T. Organometallics 2011, 30, 1319.
(49) Cochrane, S. A.; Huang, Z.; Vederas, J. C. Organic & Biomolecular Chemistry 2013, 11, 630.
(50) Trost, B. M.; Rudd, M. T. Org. Lett. 2003, 5, 4599.
(51) Trost, B. M.; Miller, J. R.; Hoffman, C. M. J. Am. Chem. Soc.2011, 133, 8165.
(52) Mangold, S. L.; O’Leary, D. J.; Grubbs, R. H. J. Am. Chem. Soc.2014, 136, 12469.
(53) Nocentini, A.; Carta, F.; Ceruso, M.; Bartolucci, G.; Supuran, C. T. Bioorg. Med. Chem. 2015, 23, 6955.
(54) Pardon, K. H.; Graney, S. D.; Capone, D. L.; Swiegers, J. H.; Sefton, M. A.; Elsey, G. M. J. Agric. Food. Chem. 2008, 56, 3758.
(55) Wang, Y.; Ji, K.; Lan, S.; Zhang, L. Angew. Chem. Int. Ed. 2012, 51, 1915.
(56) Llewellyn, D. B.; Wahhab, A. Tetrahedron Letters. 2009, 50, 3939.
(57) Crich, D.; Rahaman, M. Y. J. Am. Chem. Soc. 2009, 74, 6792.