請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/16911
標題: 利用氯化銅進行三步一鍋化合成苯駢[b]噻吩衍生物並應用於雷洛昔芬合成之研究
The study in copper(II) chloride-mediated one-pot three-step syntheses of benzo[b]thiophene derivatives and its application for the total synthesis of raloxifene
作者: 薛清文
Xue, Qing-Wen
關鍵字: copper chloride
三步一鍋化
one-pot three-step
benzo[b]thiophene
raloxifene
苯駢噻吩
雷洛昔芬
出版社: 化學系所
引用: 1.Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054-3131. 2.Razzuk, A.; Biehl, E. R. J. Org. Chem. 1987, 52, 2619-2622. 3.Mitchell, H.; Leblanc, Y. J. Org. Chem. 1994, 59, 682-687. 4.Ma, D.; Liu, F. Chem. Commun. 2004, 1934-1935. 5.Bourdreux, Y.; Nowaczyk, S.; Billaud, C.; Mallinger, A.; Willis, C.; Desage-El Murr, M.; Toupet, L.; Lion, C.; Le Gall, T.; Mioskowski, C. J. Org. Chem. 2007, 73, 22-26. 6.Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337-2364. 7.Kohei, T.; Miyaura, N. Topics in Current Chemistry, 2002, 219, 1-9. 8.Agrofoglio, L. A.; Gillaizeau, I.; Saito, Y. Chem. Rev. 2003, 103, 1875-1916. 9.(a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467-4470; (b) Sonogashira, K. J. Organomet. Chem. 2002, 653, 46-49; (c) Sonogashira, K. In Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., de Meijera, A., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 1, p 319; (d) Sonogashira, K. In Comprehensive Organic Synthesis; Trost, B. M., Fleing, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, p 521. 10.(a) Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636-3638; (b) Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem. Lett. 1977, 3, 301-302; (c) Scott, W. J.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033-3040; (d) Piers, E.; Friesen, R. W.; Keay, B. A. Tetrahedron 1991, 47, 4555-4570. 11.(a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483; (b) Snieckus, V. Chem. Rev. 1990, 90, 879-933; (c) Matteson, D. S. Tetrahedron 1989, 45, 1859-1885; (d) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 20, 3437-3440; (e) Miyaura, N.; Satoh, M.; Suzuki, A. Tetrahedron Lett. 1986, 27, 3745-3748. 12.(a) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518-5526; (b) Plevyak, J. E.; Dickerson, J. E.; Heck, R. F. J. Org. Chem. 1979, 44, 4078-4080; (c) Cortese, N. A.; Ziegler, C. B.; Hrnjez, B. J.; Heck, R. F. J. Org. Chem. 1978, 43, 2952-2958. 13.(a) Deng, W.; Wang, Y.-F.; Zou, Y.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2004, 45, 2311-2315; (b) Antilla, J. C.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 11684-11688; (c) Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421-7428. 14.(a) Ullmann, F. Ber. Dtsch. Chem. Ges. 1903, 36, 2382-2384; (b) Ullmann, F.; Bielecki, J. Ber. Dtsch. Chem. Ges. 1901, 34, 2174-2185. 15.Goldberg, I. Ber. Dtsch. Chem. Ges. 1906, 39, 1691-1692. 16.Hurtley, W. R. H. J. Chem. Soc. 1929, 1870-1873. 17.(a) Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727-7729; (b) Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421-7428; (c) Antilla, J. C.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 11684-11688. 18.(a) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108, 3054-3131; (b) Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001, 3, 4315-4317; (c) Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1996, 118, 2748-2749; (d) Xie, X.; Cai, G.; Ma, D. Org. Lett. 2005, 7, 4693-4695; (e) Chen, Y.-J.; Chen, H.-H. Org. Lett. 2006, 8, 5609-5612. 19.Zhang, S.-L.; Liu, L.; Fu, Y.; Guo, Q.-X. Organometallics 2007, 26, 4546-4554. 20.Cristau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M. Chem. Eur. J. 2004, 10, 5607-5622. 21.陳敏為,甘禮騅(1990年6月)《有機雜環化合物》(第一版),北京;高等教育出版社。 22.Larock, R. C.; Yue, D. Tetrahedron Lett. 2001, 42, 6011-6013. 23.Flynn, B. L.; Verdier-Pinard, P.; Hamel, E. Org. Lett. 2001, 3, 651-654. 24.Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem. Int. Ed. 2006, 45, 4473-4475. 25.Lu, W.-D.; Wu, M.-J. Tetrahedron 2007, 63, 356-362. 26.(a) Larock, R. C. In Comprehensive Organic Transformations, 2nd ed.; John Wiley & Sons: New York, 1999; pp 1707-1708; (b) Kleemann, A.; Engel, J.; Kutscher, B.; Reichert, D. Pharmaceutical substances syntheses, patents, applications, 4th ed.; Georg Thieme: Stuttgart, 2001; (c) Sundermeier, M.; Zapf, A.; Beller, M. Eur. J. Inorg. Chem. 2003, 3513-3526. 27.(a) Ellis, G. P.; Romney-Alexander, T. M. Chem. Rev. 1987, 87, 779-794; (b) Lindley, J. Tetrahedron 1984, 40, 1433-1456; (c) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651-2710. 28.Beletskaya, I. P.; Sigeev, A. S.; Peregudov, A. S.; Petrovskii, P. V. J. Organomet. Chem. 2004, 689, 3810-3812. 29.(a) Nowak, I.; Ziolek, M. Chem. Rev. 1999, 99, 3603-3624; (b) Lucke, B.; Narayana, K. V.; Martin, A.; Jahnisch, K. Adv. Synth. Catal. 2004, 346, 1407-1424. 30.Takagi, K.; Okamoto, T.; Sakakibara, Y.; Oka, S. Chem. Lett. 1973, 2, 471-474. 31.(a) Sekiya, A.; Ishikawa, N. Chem. Lett. 1975, 4, 277-278; (b) Chatani, N.; Hanafusa, T. J. Org. Chem. 1986, 51, 4714-4716. 32.(a) Percec, V.; Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60, 6895-6903; (b) Grushin, V. V.; Alper, H. Chem. Rev. 1994, 94, 1047-1062; (c) Sasaki, K.; Sakai, M.; Sakakibara, Y.; Takagi, K. Chem. Lett. 1991, 20, 2017-2018. 33.(a) Erhardt, S.; Grushin, V. V.; Kilpatrick, A. H.; Macgregor, S. A.; Marshall, W. J.; Roe, D. C. J. Am. Chem. Soc. 2008, 130, 4828-4845; (b) Arvela, R. K.; Leadbeater, N. E. J. Org. Chem. 2003, 68, 9122-9125; (c) Sundermeier, M.; Zapf, A.; Beller, M. Eur. J. Inorg. Chem. 2003, 3513-3526; (d) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234-245. 34.Wang, D.; Kuang, L.; Li, Z.; Ding, K. Synlett 2008, 69-72. 35.Zanon, J.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 2890-2891. 36.Cristau, H.-J.; Ouali, A.; Spindler, J.-F.; Taillefer, M. Chem. Eur. J. 2005, 11, 2483-2492. 37.Schareina, T.; Zapf, A.; Magerlein, W.; Muller, N.; Beller, M. Chem. Eur. J. 2007, 13, 6249-6254. 38.Fournier Dit Chabert, J.; Joucla, L.; David, E.; Lemaire, M. Tetrahedron 2004, 60, 3221-3230. 39.Hatsuda, M.; Seki, M. Tetrahedron Lett. 2005, 46, 1849-1853. 40.Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963, 28, 3313-3315. 41.Dieck, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93, 259-263. 42.Cassar, L. J. Organomet. Chem. 1975, 93, 253-257. 43.Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467-4470. 44.(a) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem. Int. Ed. 2000, 39, 2632-2657; (b) Hay, A. S. J. Org. Chem. 1962, 27, 3320-3321; (c) Kotora, M.; Takahashi, T. In Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E., de Meijere, A., Eds.; Wiley-Interscience: New York, 2002; p 973. 45.Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874-922. 46.Gottardo, C.; Kraft, T. M.; Hossain, M. S.; Zawada, P. V.; Muchall, H. M. Can. J. Chem. 2008, 86, 410-415. 47.Okuro, K.; Furuune, M.; Enna, M.; Miura, M.; Nomura, M. J. Org. Chem. 1993, 58, 4716-4721. 48.Li, J.-H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu, X.-C. J. Org. Chem. 2007, 72, 2053-2057. 49.Ma, D.; Liu, F. Chem. Commun. 2004, 1934-1935. 50.(a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4442-4489; (b) Giese, M. W.; Moser, W. H. J. Org. Chem. 2005, 70, 6222-6229; (c) Sumi, S.; Matsumoto, K.; Tokuyama, H.; Fukuyama, T. Org. Lett. 2003, 5, 1891-1893. 51.(a) Tour, J. M. Acc. Chem. Res. 2000, 33, 791-804; (b) Martin, R. E.; Diederich, F. Angew. Chem. Int. Ed. 1999, 38, 1350-1377; (c) Tour, J. M. Chem. Rev. 1996, 96, 537-554; (d) Bunz, U. H. F. Chem. Rev. 2000, 100, 1605-1644; (e) Arnt, L.; Breitenkamp, R. B.; Tew, G. N. Polym. Adv. Technol. 2005, 16, 189-194; (f) Weder, C. Chem. Commun. 2005, 5378-5389. 52.(a) Electronic Materials: The Oligomer Approach; Mullen, K., Wegner, G., Eds.; Wiley-VCH: Weinheim, 1998; (b) Nalwa, H. S.; Miyata, S. Nonlinear Optics of Organic Molecules and Polymers; CRC Press: Boca Raton, FL, 1997; (c) Supramolecular Photosensitive and Electroactive Materials; Nalwa, H. S., Ed.; Academic Press: San Diego, CA, 2001; (d) Acetylene Chemistry. Chemistry, Biology and Material Science; Diederich, F., Stang, P. J., Tykwinski, R. R. Eds.; Wiley-VCH: Weinheim, 2005. 53.Mehta, S.; Larock, R. C. J. Org. Chem. 2010, 75, 1652-1658. 54.(a) Smith, M. R.; Fallon, M. A.; Lee, H.; Finkelstein, J. S. J. Clin. Endocrinol. metab. 2004, 89, 3841-3846; (b) Siris, E. S.; Harris, S. T.; Eastell, R.; Zanchetta, J. R.; Goemaere, S.; Diez-Perez, A.; Stock, J. L.; Song, J.; Qu, Y.; Kulkarni, P. M.; Siddhanti, S. R.; Wong, M.; Cummings, S. R. J. Bone Miner. Res. 2005, 20, 1514-1524; (c) Grady, D.; Cauley, J. A.; Geiger, M. J.; Kornitzer, M.; Mosca, L.; Collins, P.; Wenger, N. K.; Song, J.; Mershon, J.; Barrett-Connor, E. J. Natl. Cancer Inst. 2008, 100, 854-861; (d) Deal, C.; Omizo, M.; Schwartz, E. N.; Eriksen, E. F.; Cantor, P.; Wang, J.; Glass, E. V.; Myers, S. L.; Krege, J. H. J. Bone Miner. Res. 2005, 20, 1905-1911; (e) Qin, Z.; Kastrati, I.; Chandrasena, R. E. P.; Liu, H.; Yao, P.; Petukhov, P. A.; Bolton, J. L.; Thatcher, G. R. J. J. Med. Chem. 2007, 50, 2682-2692; (f) Barrett-Connor, E.; Mosca, L.; Collins, P.; Geiger, M. J.; Grady, D.; Kornitzer, M.; McNabb, M. A.; Wenger, N. K. N. Engl. J. Med. 2006, 355, 125-137; (g) Palkowitz, A. D.; Glasebrook, A. L.; Thrasher, K. J.; Hauser, K. L.; Short, L. L.; Phillips, D. L.; Muehl, B. S.; Sato, M.; Shetler, P. K.; Cullinan, G. J.; Pell, T. R.; Bryant, H. U. J. Med. Chem. 1997, 40, 1407-1416. 55.Vogel, V. G.; Costantino, J. P.; Wickerham, D. L.; Cronin, W. M.; Cecchini, R. S.; Atkins, J. N.; Bevers, T. B.; Fehrenbacher, L.; Pajon, E. R.; Wade, J. L.; Robidoux, A.; Margolese, R. G.; James, J.; Lippman, S. M.; Runowicz, C. D.; Ganz, P. A.; Reis, S. E.; McCaskill-Stevens, W.; Ford, L. G.; Jordan, V. C.; Wolmark, N.; Breast, f. t. N. S. A.; Project, B. JAMA 2006, 295, 2727-2741. 56.(a) Jones, C. D.; Suarez, T. U.S. Patent 4,133,814; (b) Jones, C. D.; Jevnikar, M. G.; Pike, A. J.; Peters, M. K.; Black, L. J.; Thompson, A. R.; Falcone, J. F.; Clemens, J. A. J. Med. Chem. 1984, 27, 1057-1066. 57.Godfrey, A. G. U.S. Patent 5,466,810. 58.Schmid, C. R.; Sluka, J. P.; Duke, K. M. Tetrahedron Lett. 1999, 40, 675-678. 59.Shinde, P. S.; Shinde, S. S.; Renge, A. S.; Patil, G. H.; Rode, A. B.; Pawar, R. R. Lett. Org. Chem. 2009, 6, 8-10. 60.(a) Takimiya, K.; Kunugi, Y.; Toyoshima, Y.; Otsubo, T. J. Am. Chem. Soc. 2005, 127, 3605-3612; (b) Ebata, H.; Miyazaki, E.; Yamamoto, T.; Takimiya, K. Org. Lett. 2007, 9, 4499-4502. 61.陳鴻志論文,2009,國立中興大學陳耀鐘老師實驗室。 62.林哲毅論文,2010,國立中興大學陳耀鐘老師實驗室。 63.Cho, C.-H.; Neuenswander, B.; Lushington, G. H.; Larock, R. C. J. Comb. Chem. 2009, 11, 900-906. 64.連瑞政論文,2010,國立中興大學陳耀鐘老師實驗室。 65.Castanet, A.-S.; Colobert, F.; Broutin, P.-E. Tetrahedron Lett. 2002, 43, 5047-5048. 66.顏千雯論文,2005,國立中興大學陳耀鐘老師實驗室。 67.Fournier Dit Chabert, J.; Gozzi, C.; Lemaire, M. Tetrahedron Lett. 2002, 43, 1829-1833. 68.Marron, K. S.; Schmid, C. R.; Sluka, J. P. Eur. Pat. Appl. EP838464 A1 980429. 69.Yu, B.; Qin, Z.; Wijewickrama, G. T.; Edirisinghe, P.; Bolton, J. L.; Thatcher, G. R. J. Bioconjugate Chem. 2009, 20, 728-741.
摘要: (I)本實驗室開發出一個不使用鈀金屬和配位基催化的三步一鍋化反應,此催化系統是利用氯化銅來取代鈀金屬的使用,其有便宜和容易從產物中移除的優點,同時可方便應用於合成出一系列苯駢[b]噻吩衍生物。 (II)本實驗室開發的一鍋三步化反應,已成功應用於雷洛昔芬之合成,合成過程有7個步驟,總產率約21%。起始物使用2-碘-5甲氧基苯硫醚55經過碘化反應得到化合物56,緊接著利用氯化銅催化一鍋三步化反應做為關鍵步驟得到化合物58,最後經過格林納加成反應、去甲氧基保護和親核性芳香環取代反應得到雷洛昔芬62。
(I)A palladium- and ligand-free reaction condition for Sonogashira-type coupling was developed, which used CuCl2 as the catalyst system and was applicable to one-pot three-steps synthesis of benzo[b]thiophene derivatives. Since this catalyst is cheap and easily removable (by washing), it may have some practical usage for chemists. (II)Total synthesis of raloxifene was accomplished in seven steps in 21% of total yields. This novel route was starting from the corresponding thioanisole 55. The iodination of compound 55 by treating with NIS in the presence of TMSCl can provide the 46% yield of the desired iodothioanisole 56. After the CuCl2-promoted one-pot three-step protocol was employed to iodothioanisole 56 as the key step for the construction of benzo[b]thiophene skeleton 58, the further three steps were carried out via Grignard reagent addition, deprotection, and SNAr reaction to afford the raloxifene 62.
URI: http://hdl.handle.net/11455/16911
其他識別: U0005-2607201107315000
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2607201107315000
顯示於類別:化學系所

文件中的檔案:
檔案 描述 大小格式 
nchu-101-7099051044-1.pdf8.46 MBAdobe PDF檢視/開啟


在 DSpace 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。