臺灣博碩士論文加值系統

本論文研究掩飾鄰苯之Diels-Alder反應，以及掩飾鄰苯之合成應用，內容共分為兩部份：第一部份係探討掩飾鄰苯與碳六十之Diels-Alder反應；第二部份係應用掩飾鄰苯於天然物(±)- magellanine（52）之全合成。
第一部份：各種掩飾鄰苯19與碳六十（1）進行Diels-Alder反應，可以製備出新的且多官能基雙環[2.2.2]辛烯酮類碳六十之衍生物35。
第二部份：可直接購得之17d為起始物，經由二乙醯基亞碘苯氧化、分子間Diels-Alder反應、照光反應、選擇性保護酮基反應及自由基開環反應可得到線性參環戊烷架構的化合物152。
化合物152經由三個步驟官能基轉換和1,4-加成反應生成化合物150，再經過選擇性還原酮基、保護、以及分子內合環反應獲得化合物149，後者經由氧化斷裂、兩次還原胺化反應和去保護得到天然物(±)- magellanine（52），總共用了16步，總產率為12.1%。
將化合物170直接進行分子內合環反應生成化合物177。再經由氧化斷裂、兩次還原胺化反應獲得天然物(±)-magellanine（52），總共用了14步，總產率為9.1%。

The thesis consists of two parts: The first part is concerned with Diels-Alder reactions of masked o-benzoquinones (MOBs) 19 with [60]fullerene (1) and the second part describes the applications of MOBs in the synthesis of (±)-magellanine (52).
The Diels-Alder reactions of various MOBs with [60]fullerene, affording novel and highly functionalized bicyclo[2.2.2]octenone-fused [60]fullerene derivatives 35 is discussed in the chapter 1.
In the chapter 2, the total synthesis of (±)-magellanine (52) is presented. The linearly fused triquinane 152 was obtained by means of sequential intermolecular Diels-Alder reaction of an MOB generated in situ by DAIB mediated oxidation of acetovanillone (17d) in methanol followed by the photochemical oxa-di-p-methane rearrangement, selective protection of aceto functionality and the opening of a strained cyclopropane-ring.
The transformation of triquinane 152 into compound 150 was achieved by functional group manipulations and 1,4-addition of a diallylcyanocuprate reagent. Tetracyclic compound 149 was obtained from compound 150 by selective reduction; protection and intramolecular cyclization. Finally, the total synthesis of (±)-magellanine (52) was accomplished by means of sequential regiospecific oxidative cleavage of cyclopentene ring of 149, double reductive amination followed by deprotection of TBS group. Thus, the total synthesis of (±)-magellanine (52) was achieved in 12.1% overall yield from commercially available acetovanillone (17d) in sixteen synthetic operations.
Alternatively, the triquinane compound 170 was cyclized intramolecularly into tetracyclic 177. Subsequently, 177 was subjected to sequential regiospecific oxidative cleavage followed by double reductive amination to afford the targeted molecule (±)-magellanine (52), in 9.1% overall yield from commercially available acetovanillone (17d) in fourteen steps.

中文摘要………………………………………………………………… i
英文摘要…………………………………………………………………ii
謝誌…………………………………………………………………….. iii
縮寫對照表…………………………………………………………….. iv
目錄…………………………………………………………………….. vi
第一章 掩飾鄰苯與碳六十的Diels-Alder反應之研究……………..1
第一節 緒論……………………………………………………..…..1
1-1-1 碳六十之簡介………………………………………..…..1
1-1-2 碳六十的Diels-Alde反應之回顧………………………5
第二節 掩飾鄰苯之文獻回顧…………………………………...9
1-2-1 掩飾鄰苯之製備………………………………………9
1-2-2 掩飾鄰苯之性質………………………………………9
1-2-3 掩飾鄰苯之Diels-Alder反應………………………..11
（一）掩飾鄰苯與烯類之Diels-Alder反應………....11
(1) 與烯類分子間之Diels-Alder反應……………...11
(2) 與烯類分子內之Diels-Alder反應……………...12
（二）掩飾鄰苯與雙烯類之Diels-Alder反應……....13
(1) 與雙烯類分子間之Diels-Alder反應…………...13
(2) 與雜環雙烯類分子間之Diels-Alder反應……...14
(3) 與雙烯類分子內之Diels-Alder反應…………...14
1-2-4 研究動機………………………………………………..15
第三節 結果與討論……………………………………………….16
1-3-1 掩飾鄰苯之製備……………………………………..16
1-3-2 掩飾鄰苯與碳六十進行Diels-Alder反應之結果與討
論……………………………………………………….17
1-3-3 結構鑑定……………………………………………….23
1-3-4 理論計算……………………………………………….26
第三節 結論……………………………………………………….28
第二章 天然物(±)-Magellanine之全合成…………………………….29
第一節 緒論……………………………………………………….29
第二節 研究構想………………………………………………….42
第三節 逆合成分析……………………………………………….44
第四節 結果與討論……………………………………………….46
2-4-1 線性參環戊烷化合物152之合成…………………….46
2-4-2 烯酮化合物151之合成……………………………….50
2-4-3 肆環化合物149之合成……………………………….53
2-4-4 天然物(±)-magellanine（52）之合成..……………….60
第五節 結論………………………………………………………72
第三章 實驗部份………………………………………………………75
第一節 一般實驗方法…………………………………………….75
第二節 掩飾鄰苯與碳六十之Diels-Alder反應的實驗步驟與光
譜資料…………………………………………………….79
3-2-1 化合物40的合成………………………………………79
3-2-2 化合物17c的合成……………………………………...80
3-2-3 化合物41的合成………………………………………81
3-2-4 化合物43的合成………………………………………82
3-2-5 化合物45的合成……………………………………….83
3-2-6 化合物47的合成………………………………………84
3-2-7 化合物51的合成………………………………………85
3-2-8 化合物19f的合成……………………………………...86
3-2-9 化合物19g的合成……………………………………..87
3-2-10 化合物19h的合成……………………………………88
3-2-11 化合物19i的合成…………………………………….89
3-2-12 化合物19j的合成…………………………………….90
3-2-13 化合物19k的合成……………………………………91
3-2-14 化合物19l的合成…………………………………….92
3-2-15 化合物35a的合成……………………………………93
3-2-16 化合物35b的合成……………………………………95
3-2-17 化合物35c的合成…………………………………….96
3-2-18 化合物35d的合成……………………………………97
3-2-19 化合物35e的合成…………………………………….99
3-2-20 化合物35f的合成…………………………………....100
3-2-21 化合物35g的合成…………………………………...101
3-2-22 化合物35h的合成…………………………………..102
3-2-13 化合物35i的合成……………………………………104
第三節 天然物(±)-Magellanine之全合成的實驗步驟與光譜資料 ………………106
3-3-1 化合物154的合成……………………………………106
3-3-2 化合物153的合成…………………………………..107
3-3-3 化合物157的合成…………………………………..108
3-3-4 化合物152的合成…………………………………..109
3-3-5 化合物161的合成…………………………………..110
3-3-6 化合物162的合成…………………………………..111
3-3-7 化合物163的合成…………………………………..112
3-3-8 化合物151的合成…………………………………..114
3-3-9 化合物165的合成…………………………………..115
3-3-10 化合物150的合成………………………………….116
3-3-11 化合物170的合成………………………………….117
3-3-12 化合物171的合成………………………………….118
3-3-13 化合物149的合成………………………………….119
3-3-14 化合物173的合成………………………………….121
3-3-15 化合物176的合成………………………………….123
3-3-16 化合物176的合成………………………………….124
3-3-17 化合物(±)-52的合成……………………………….125
3-3-18 化合物177的合成………………………………….126
3-3-19 化合物(±)-52的合成……………………………….127
第四節 參考資料………………………………………………...129
附錄…………………………………………………136

1.Kroto, H. W.; Heath, J. R.; O''Brien, S. C.; Curl, R. F.; Smalley, E. E. Nature 1985, 318, 162.
2.Kratschmer, W; Lamb, L. D.; Fostiropoulos, K.; Huffmann, D. R. Nature 1990, 347, 354.
3.Scrirens, W. A.; Bedworth, P. V.; Tour, J. M. J. Am. Chem. Soc. 1992, 114, 7917.
4.Hirsch, A. The Chemistry of the Fullerenes; Thieme: Stuttgart, 1994, p. 3.
5.Hawkins, J. M.; Meyer, A.; Lewis, T. A.; Loren, S.; Hollander, F. J. Science 1991, 252, 312.
6.(a) Hirsch, A. The Chemistry of the Fullerenes; Thieme: Stuttgart, 1994, p. 32. (b) Hirsch, A. The Chemistry of the Fullerenes; Thieme: Stuttgart, 1994, p. 30.
7.Johnson, R. D.; Meijer, G.; Bethune, D. S. J. Am. Chem. Soc. 1990, 112, 8983.
8.Haddon, R. C.; Brus, L. E.; Raghavachari, K. Chem. Phys. Lett. 1986, 125, 459.
9.Ohno, M.; Azuma, T.; Kojima, S.; Shirakawa, Y.; Eguchi, S. Tetrahedron 1996, 52, 4983.
10.(a) Hirsch, A. Angew. Chem. Int. Ed. Engl. 1993, 32, 1138. (b) Bouto- rine, A.; Tokuyama, H.; Takasugi, M.; Isobe, H.; Nakamura, E.; Helene, C. Angew. Chem. Int. Ed. Engl. 1994, 33, 2462. (c) Yamako- shi, Y. N.; Yagami, T.; Sueyoshi, S.; Miyata, N. J. Org. Chem. 1996, 61, 7236. (d) Higashi, N.; Inoue, T.; Niwa, M. Chem. Commun. 1997, 1507. (e) Ros, D. T.; Prato, M. Chem. Commun. 1999, 663.
11.(a) Schinazi, R. F.; Sijbesma, R. P.; Srdanov, G.; Hill, C. L.; Wudl, F. Antimicrob. Agents Chemother. 1993, 37, 1707. (b) Nakamura, E.; Tokuyama, H.; Yamago, S.; Shiraki, T.; Sugiura, Y. Bull. Chem. Soc. Jpn. 1996, 69, 2143. (c) Friedman, S. H.; Ganapathi, P. S.; Rubin, Y.; Kenyon, G. L. J. Med. Chem. 1998, 41, 2424.
12.Li, L.-S.; Hu, Y.-J.; Wu, Y.; Wu, Y.-L.; Yue, J.; Yang, F. J. Chem. Soc. Perkin Trans. 1 2001, 617.
13.Belik, P.; Gugel, A.; Spickermann, J.; Mullen, K. Angew. Chem. Int. Ed. Engl. 1993, 32, 78.
14.Diederich, F.; Jonas, U.; Gramlich, V.; Herrmann, H.; Ringsdorf, H.; Thilgen, C. Helv. Chim. Acta 1993, 76, 2445.
15.Gugel, A.; Kraus, A.; Spikermann, J.; Belik, P.; Mullen, K. Angew. Chem. Int. Ed. Engl. 1994, 33, 559.
16.Iyoda, M.; Sultana, F.; Sasaki, S.; Yoshida, M. J. Chem. Soc., Chem. Commun. 1994, 1929.
17.Zhang, X.; Foote, C. S. J. Org. Chem. 1994, 59, 5235.
18.Bidell, W.; Douthwaite, R. E.; Green, M. L. H.; Stephens, A. H. H.; Turner, J. F. C. J. Chem. Soc., Chem. Commun. 1994, 1641.
19.Tsuda, M.; Ishida, T.; Nogami, T.; Kurono, S.; Ohashi, M. J. Chem. Soc., Chem. Commun. 1993, 1296.
20.Prato, M.; Suzuki, T.; Foroudian, H.; Li, Q.; Khemani, K.; Wudl, F.; Little, T.; Rickborn, B.; Yamago, S.; Nakamura, E. J. Am. Chem. Soc. 1993, 115, 1594.
21.Krautler, B.; Puchberger, M. Helv. Chim. Acta 1993, 76, 1626.
22.Rubin, Y.; Khan, S.; Freedberg, D. I.; Yeretzian, C. J. Am. Chem. Soc. 1993, 115, 344.
23.An, Y.-Z.; Anderson, J. L.; Rubin, Y. J. Org. Chem. 1993, 58, 4799.
24.Ohno, M.; Azuma, T.; Kojima, S.; Shirakawa, Y.; Eguchi, S. Tetrahedron 1996, 52, 4983.
25.Ohno, M.; Shirakawa, Y.; Eguchi, S. Synthesis 1998, 1812.
26.Mori, S.; Karita, T.; Komatsu, K.; Sugita, N.; Wan, T. S. M. Synth. Commun. 1997, 27, 1475.
27.Liou, K.-F.; Hsiao, T.-Y.; Cheng, C.-H.; Fullerene Sci. Tech. 1998, 6, 351.
28.McKillop, A.; Perry, D. H.; Edward, M.; Antus, S.; Farkas, L.; Nogradi, M.; Taylor, E. C. J. Org. Chem. 1976, 41, 282.
29.(a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic Press: San Diego, 1997. (b) Tamura, Y.; Yakura, T.; Harnata, J. I.; Kita, Y. J. Org. Chem. 1987, 52, 3927. (c) Yahura, T.; Tohma, H.; Kikchi, K.; Kita, Y. Synthesis 1989, 126. (d) Kurti, L.; Herczegh, P.; Visy, J.; Simonyi, M.; Antus, S.; Pelter, A. J. Chem. Soc. Perkin Trans. 1 1999, 379. (e) Tohma, H.; Morioka, H.; Takizawa, S; Arisawa, M; Kita, Y. Tetrahedron 2001, 57, 345 and references therein.
30.(a) Liao, C.-C. "Synthetic Applications of Masked Benzoquinones," In Modern Methodology in Organic Synthesis, Proceeding of the 1991 International Symposium of Organic Reactions, Kyoto; Sheno, T. Ed.; Kodansha: Tokyo, 1992; p 409. (b) Liao, C.-C.; Peddinti, R. K.; Acc. Chem. Res. Accepted for publication.
31.Ko, S. unpublished results.
32.(a) Andersson, G.; Berntsson, P. Acta Chem. Scand. B 1975, 29, 948. (b) Andersson, G. Acta Chem. Scand. B 1976, 30, 403.
33.Liao, C.-C.; Chu, C.-S.; Lee, T.-H.; Rao, P.D.; Ko, S.; Song, L.-D.; Hsiao, H.-C. J. Org. Chem. 1999, 64, 4102.
34.(a) Gao, S.-Y.; Lin, Y.-L.; Rao, P. D.; Liao, C.-C. Synlett 2000, 421. (b) Gao, S.-Y; Ko, S; Lin, Y.-L; Peddinti, R. K; Liao, C.-C. Tetrahedron 2001, 57, 297.
35.Chu, C.-S.; Lee, T.-H.; Rao, P. D.; Song, L.-D.; Liao, C.-C. J. Org. Chem. 1999, 64, 4111.
36.Hsu, D.-S.; Rao, P. D.; Liao, C.-C.Chem. Commun. 1998,1795.
37.Rao, P. D.; Chen, C.-H.;. Liao, C.-C. Chem. Commun. 1998, 155
38.Chen, C.-H.; Rao, P. D.; Liao C.-C. J. Am. Chem. Soc. 1998, 120, 13254.
39.(a) Hsieh, M.-F.; Rao, P. D.; Liao, C.-C. Chem. Commun. 1999, 1141. (b) Hsieh, M.-F.; Peddinti, R. K.; Liao, C.-C. Tetrahedron Lett. 2001, 42, 5481.
40.Lai, C.-H.; Ko, S.; Rao, P. D.; Liao, C.-C. Tetrahedron Lett. 2001, 42, 7851.
41.Hsiu, P.-Y.; Liao, C.-C. Chem. Commun. 1997, 1085.
42.(a) 宋玲端碩士論文, 國立清華大學, 1991年. (b) 沈意綾碩士論文, 國立清華大學, 1993年. (c) Coleman, R. S.; Grant, E. B. J. Am. Chem. Soc. 1995, 117, 10889. (d) 王明男碩士論文, 國立清華大學, 1997年. (e) Lai, C.-H.; Shen, Y.-L.; Liao C.-C. Synlett 1997, 1351. (f) 陳耀光博士論文, 國立清華大學, 1999年.
43.Hou, H.-F. ; Peddinti, R. K.; Liao, C.-C. manuscripted submitted.
44.Chittimalla, S. K. unpublished results.
45.(a) Castillo, M.; Morales, G.; Loyola, L. A.; Singh, I.; Calvo, C.; Holland, H. L.; MacLean,D. B. Can. J. Chem. 1975, 53, 2513. (b) Loyola, L. A.; Morales, G.; Castillo, M. Phytochemistry 1979, 18, 1721. (c) Castillo, M.; Morales, G.; Loyola, L. A.; Singh, I.; Calvo, C.; Holland, H. L.; MacLean, D. B. Can. J. Chem. 1976, 54, 2893. (d) Castillo, M.; Morales, G.; Loyola, L. A.; Singh, I.; Calvo, C.; Holland, H. L.; MacLean, D. B. Can. J. Chem. 1976, 54, 2900.
46.(a) Hirst, G. C.; Johnson, T. O.; Overman, L. E. J. Am. Chem. Soc. 1993, 115, 2992. (b) Paquette, L. A.; Friedrich, D.; Pinard, E.; Williams, J. P.; St. Laurent, D. S.; Roden, B. A. J. Am. Chem. Soc. 1993, 115, 4377. (c) Williams, J. P.; St. Laurent, D. S.; Friedrich, D.; Pinard, E.; Roden, B. A.; Paquette, L. A. J. Am. Chem. Soc. 1994, 116, 4689. (d) Sha, C.-K.; Lee, F.-K.; Chang, C.-J. J. Am. Chem. Soc. 1999, 121, 9875. (e) Mehta, G. Rao, K. S. J. Chem. Soc., Chem. Commun. 1987, 1578. (f) Mehta, G.; Reddy, M. S. Tetrahedron Lett. 1990, 31, 2039. (g) Mehta, G.; Reddy, M. S.; Thomas, A. Tetrahedron 1998, 54, 7865. (h) Sandham, D. A.; Meyers, A. I. J. Chem. Soc. Chem. Commun. 1995, 24, 2511. (i) Ishizaki, M.; Niimi, Y.; Hoshino, O. Chem. Lett. 2001, 546. (j) Crimmins, M. T.; Watson, P. S. Tetrahedron Lett. 1993, 34, 199.
47.Collington, E. W.; Wallis, C. J.; Waterhouse, I. Tetrahedron Lett. 1983, 24, 3125.
48.St. Laurent, D. R.; Paquette, L. A. J. Org. Chem. 1986, 51, 3861.
49.Caine, D.; Procter, K.; Cassell, R. A. J. Org. Chem. 1984, 49, 2647.
50.Baraldi, P. G.; Barco, A.; Benetti, S.; Pollini, G. P.; Zanirato, V. Tetrahedron Lett. 1984, 25, 4291.
51.Crimmins, M. T.; Nantermet, P. G. J. Org. Chem., 1990, 55, 4235.
52.Rezgui, F.; Gaied, M. M. E. Tetrahedron Lett. 1998, 39, 5965.
53.(a) Liao, C.-C.; Wei, C.-P. Tetrahedron Lett. 1989, 30, 2255. (b) Chu, C.-S.; Liao, C.-C.; Rao, P. D. Chem. Commun. 1996, 1537. (c) Lee, T.-H.; Liao, C.-C. Tetrahedron Lett. 1996, 37, 6869. (d) Liu, W.-C.; Liao C.-C. Synlett 1998, 912. (e) Liu, W.-C.; Liao C.-C. Chem. Commun. 1999, 117. (f) Hsu, D.-S.; Hsu, P.-Y.; Liao. C.-C. Org. Lett. 2001, 3, 263. (g) Hsu, D.-S. unpublished results.
54.(a) Givens, R. S.; Oettle, W. F.; Coffin, R. L.; Carlson, R. G. J. Am. Chem. Soc. 1971, 93, 3957. (b) Givens, R. S.; Oettle, W. F. J. Am. Chem. Soc. 1971, 93, 3963.
55.Enholm, E. J.; Jia, Z. J. J. Org. Chem. 1997, 62, 174.
56.(a) Pappo, R.; Allen, D. S., Jr.; Lemieux, R. U.; Johnson, W. S. J. Org. Chem. 1956, 21, 478. (b) Vanrheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 23, 1973.
57. (a) Borch, R. F.; Bernstein, M. D.; Durst, H. D. J. Am. Chem. Soc. 1971, 93, 2897. (b) Danheiser, R. L.; Morin, J. M., Jr.; Salaski, E. J. J. Am. Chem. Soc. 1985, 107, 8066.
58.(a) Yashida, K.; Nakajima, S.; Wakamatsu, T.; Ban, Y.; Shibasaki, M. Hetercycles 1988, 27, 1167. (b) Anwer, M. K.; Spatola, A. F. Synthesis 1980, 929. (c) Felix, A. M.; Heimer, E. P.; Lambros, T. J.; Tzougraki, C.; Meienhofer, J. J. Org. Chem. 1978, 43, 4194. (d) Congreve, M. S.; Davison, E. C.; Fuhry, M. A. M.; Holmes, A. B.; Payne, A. N.; Robinson, R. A. Ward, S. E. Synlett 1993, 663.
59.(a) Higashiyama, K.; Inoue, H.; Takahashi, H. Tetrahedron Lett. 1992, 33, 235. (b) Kozikowski, A. P.; Ma, D.; Pang, Y.-P.; Shum, P.; Likic, V.; Mishra, P. K.; Macura, S.; Basu, A. Lazo, J. S.; Ball, R. G. J. Am. Chem. Soc. 1993, 115, 3957. (c) Lakshmaiah, G.; Kawabata, T.; Shang, M.; Fuji, K. J. Org. Chem. 1999, 64, 1699. (d) Borch, R. F.; Hassid, A. J. Org. Chem. 1972, 37, 1673.
60.(a) Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43, 1011. (b) Ito, Y.; Aoyama, H.; Hirao, T.; Mochizuki, A.; Saegusa, T. J. Am. Chem. Soc. 1979, 101, 494. (c) Ito, Y.; Aoyama, H.; Saegusa, T. J. Am. Chem. Soc. 1980, 102, 4519. (d) Kende, A. S.; Roth, B.; Sanfilippo, P. J. J. Am. Chem. Soc. 1982, 104, 1784. (e) Kende, A. S.; Roth, B.; Sanfilippo, P. J.; Blacklock, T. J. J. Am. Chem. Soc. 1982, 104, 1784. (f) Kende, A. S.; Sanfilippo, P. J. Synth. Commun. 1983, 13, 715. (g) Shibasaki, M.; Mase, T.; Ikegami, S. J. Am. Chem. Soc. 1986, 108, 2090. (h) Larock, R. C.; Lee, N. H. Tetrahedron Lett. 1991, 32, 5911. (i) Toyota, M.; Seishi, T.; Fukumoto, K. Tetrahedron Lett. 1993, 34, 5947. (j) Toyota, M.; Nishikawa, Y.; Motoki, K.; Yoshida, N.; Fukumoto, K. Tetrahedron Lett. 1993, 34, 6099.
61.(a) Seyferth, D.; Weiner, M. A. J. Org. Chem. 1961, 26, 4797. (b) Whitesides, G. M.; Fischer, W. F., Jr.; Filippo, J. S., Jr.; Bashe, R. W.; House, H. O. J. Am. Chem. Soc. 1969, 91, 4871. (c) Lipshutz, B. H. Synlett 1990, 119.
62.(a) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299. (b) Comins, D. L.; LaMunyon, D. H.; Chen, X. J. Org. Chem. 1997, 26, 8182. (c) Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1984, 25, 4821. (d) Yang, M.-S.; Chang, S.-Y.; Lu, S.-S.; Rao, P. D.; Liao, C.-C. Synlett 1999, 225.
63.Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980, 21, 1357.