摘要
本论文主要利用若干串联反应合成了一些含异喹啉骨架化合物,共由以下部分组成:(1)发展了邻炔基苯甲醛腙、a,β-不饱和羰基化合物与溴的三组分反应,得到了并环的异喹啉类化合物;(2)实现了邻炔基苯甲醛肟与苯炔的串联反应,得到了一系列桥环的异喹啉类化合物。
我们发现,邻炔基苯甲醛腙、α,β-不饱和羰基化合物与溴的三组分串联反应可以很好地进行,并且反应在不同的条件可以得到不同结构的产物。当反应在70℃,以DABCO为碱的条件下,可以一步有效地合成多种取代的异喹啉并吡唑骨架化合物。当反应条件为0℃,K3PO4为碱时,得到的是1,2-二氢异喹啉骨架化合物。
同时,我们还实现了邻炔基苯甲醛肟与苯炔在三氟甲磺酸银催化下的串联环化反应。反应经过分子内环化,[3+2]环加成和重排过程,得到了一种带桥环的异喹啉类化合物。
This dissertation mainly centers on methodology development for the construction of isoquinoline compounds via tandem reactions. It is divided into two parts:(1) three-component reaction of N'-(2-alkynylbenzylidene)hydrazide, a, (3-unsaturated carbonyl compound, with bromine; (2) silver triflate-catalyzed tandem reaction of 2-alkynylbenzaldoxime with aryne.
Different outcomes were generated under different conditions for the three-component reaction of N'-(2-alkynylbenzylidene)hydrazide,α,β-unsaturated carbonyl compound, with bromine.6-BromoH-pyrazolo[5,1-α]isoquinoline was obtained when the reaction was performed in NMP at 70℃in the presence of DABCO as base, while 6-bromo-1,2,3,10b-tetrahydropyrazolo[5,1-α]isoquinoline was afforded when the reaction occurred in DMAc at 10℃in the presence of K3PO4 as base.
In the meantime, a novel and unexpected reaction of 2-alkynylbenzaldoxime with aryne in the presence of silver triflate (10 mol%) under mild conditions was discovered. This reaction proceeded through 6-endo-cyclization, [3+2] cycloaddition and rearrangement, leading to 2-oxa-6-aza-bicyclo[3.2.2]nona-6,8-diene derivatives in moderate to good yields.
引文
1. Newman, D. J.; Gragg, G. M.; Snader, K. M. J. Nat. Prod.2003,66,1022.
2. Ding, K.; Lu, Y. P.; Nikolovska-Coleska, Z.; Wang, S. M.J. Am. Chem. Soc.2001, 123,10130.
3. Vincent, G.; Williams, R. M. Angew. Chem. Int. Ed.2007,46,1517.
4. Nicolau, K. C.; Roecker, A. J.; Barluenga, S.; Pfefferkorn, J. A.; Cao, G. Chembiochem,2001,2,460.
5. Corey, E. J.; Chen, X. The logic of Chemical Synthesis [M]. New York, Wiley, 1989.
6. (a) Nicolaou, K. C.; Yang, Z.; Liu, J.; Ueno, H.; Nantermet, P. G.; Guy, R. K. Nature 1994,367,630. (b) Nicolaou, K. C.; Nantermet, P. G.; Ueno, H.; Guy, R. K.; ouladouros, E. A.; Sorensen, E. J. J. Am. Chem. Soc.1995,117,624. (c) Nicolaou, K. C.; Liu. J.; Yang, Z.; Ueno, H.; Sorensen, E. J.; Claiborne, C. F.; Guy, R. K.; Hwang. C.; Nakada, M.; Nantermet, P. G. J. Am. Chem. Soc.1995, 117,634. (d) Nicolaou, K. C.; Yang, Z.; Liu, J.; Nantermet, P. G.; Claiborne, C. F.; Renaud, J.; Guy, R. K.; Shibayama, K. J. Am. Chem. Soc.1995,117,645. (e) Nicolaou, K. C.; Ueno, H.; Liu. J.; Nantermet, P. G.; Yang, Z.; Renaud, J.; Paulvannan, K.; Chadha, R. J. Am. Chem. Soc.1995,117,653.
7. For selected examples, see:(a) Corey, E. J.; Gin, D. Y.; Kania, R. S. J. Am. Chem. Soc.1996,118,9202. (b) Cuevas, C.; Perez, M.; Martin, M. J.; Chicharro, J. L.; Fernandez-Rivas, C.; Flores, M.; Francesch, A.; Gallego, P.; Zarzuelo, M.; de la Calle, F.; Garcia, J.; Polanco, C.; Rodriguez, I.; Manzanares, I. Org. Lett.2000,2, 2545. (c) Martinez, E. J.; Corey, E. J. Org. Lett.2000,2,993. (d) Endo, A.; Yanagisawa, A.; Abe, M.; Tohma, S.; Kan, T.; Fukuyama, T. J. Am. Chem. Soc. 2002,124,6552.
8. Schreiber S. L. Science 2000,287,1964.
9. Powers, D. G.; Casebier, D. S.; Fokas. D. Tetrahedron 1998,54,4085.
10. Heerding, D. A.; Takata, D. T.; Kwon, C. S. Tetrahedron Lett.1998,39,6815.
11. For selected examples, see:(a) Weber, L. Curr. Med. Chem.2002,9,2085. (b) Povarov, L. S.; Mikohailov, B. M. Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1963,955. (c) Nicolaou, K. C.; Gao, G. Q.; Pfefferkorn, J. A. Angew. Chem. Int. Ed.2000,39,739. (d) Andreana, P. R.; Liu, C. C.; Schreiber, S. L. Org. Lett.2004,6,4231. (e) Tietze, L. F.; Rackelmann, N.; Sekar, G. Angew. Chem.Int. Ed.2003,42,4254. (f) Young, I. S.; Kerr, M. A. Angew. Chem. Int. Ed. 2003,42,3023.
12. (a) DomLing, A.; Ugi, I. Angew. Chem. Int. Ed.2000,39,3168. (b) Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P. Chem. Eur. J.2000,6,3321. (c) Weber, L. Drug Discovery Today 2002,7,143. (d) DomLing, A. Curr. Opin. Chem. Biol. 2002,6,306. (e) DomLing, A. Curr. Opin. Chem. Biol.2000,4,3318. (f) Hulme, C.; Gore, V. Curr. Med. Chem.2003,10,51.
13. Strecker, A. Liebigs Ann. Chem.1850,75,27.
14. Arend, M.; Westermann, B.; Risch, N. Angew. Chem. Int. Ed.1998,37,1044.
15. Robinson, R. J. Chem. Soc.1917,111,876.
16. Stavenger, R. A.; Schreiber, S. L. Angew. Chem. Int. Ed.2001,40,3417.
17. Nicolaou, K. C.; Pfefferkom, J. A.; Cao, G. Angew. Chem. Int. Ed.2000,39,734.
18. Nicolaou, K. C.; Pfefferkom, J. A.; Schuler, F.; Cao, G.; Casida, J. E. Chem. Biol. 2000,7,979.
19. Nicolaou, K. C.; Evans, R. M.; Roecker, A. J.; Hughes, R.; Downes, M.; Pfefferkorn, J. A. Org. Biomol. Chem.2003,1,908.
20. For selected examples, see:(a) Bently, K. W. Harwood Academic:Australia, 1998; Vol 1. (b) Trotter, B. W.; Nanda, K. K.; Kett, N. R.; Regan, C. P.; Lynch, J. J.; Stump, G. L.; Kiss, L.; Wang J.; Spencer, R. H.; Kane, S. A.; White, R. B.; Zhang R.; Anderson, K. D.; Liverton, N. J.; McIntyre, C. J.; Beshore, D. C. Hartman, G. D.; Dinsmore, C. J. J. Med. Chem.2006,49,6954. (c) Ramesh, P. Reddy, N. S.; Venkateswarlu, Y. J. Nat. Prod.1999,62,780. (d) Oi, S.; Ikedou, K.; Takeuchi, K.; Ogino, M.; Banno, Y.; Tawada, H.; Yamane, T. PCT Int. Appl. 2002,600pp (WO 2002062764 A1).
21. For selected examples, see:(a) Scott, J. D.; Williams, R. M. Chem. Rev.2002, 102,1669. (b) Chan, C.; Heid, R.; Zheng S.; Guo, J.; Zhou, B.; Furuuchi, T. Danishefsky, S. J. Am. Chem. Soc.2005,127,4596. (c) Magnus, P.; Matthews, K. S. J. Am. Chem. Soc.2005,127,12476. (d) Zheng, S.; Chan, C.; Furuuchi, T. Wright, B. J. D.; Zhou. B.; Guo, J.; Danishefsky, S. D. Angew. Chem. Int. Ed. 2006,45,1754. (e) Vincent, G.; Williams, R. M. Angew. Chem. Int. Ed.2007,46, 1517.
22.顾焕,西北大学博士学位论文,2007.
23. (a) Dai, D.;Yu, F.; Li, H. Drug Dev. Res,1996,39,138. (b) Charisson, Drugs Future 1989,14,1179. (c)冉崇昭,上海医药工业研究所博士学位论文,2000 年.(d)项勇,上海医药工业研究所硕士学位论文,2000年.
24. Gensler, W. J. In Organic Reactions; Adams, R., Ed.; Wiley:New York,1951, Vol.6,191.
25. (a) Obika, S.; Kono, H.; Yasui, Y.; Yanada, R.; Takemoto, Y. J. Org. Chem.2007, 72,4462. (b) Asao, N.; Yudha S., S.; Nogami, T.; Yamamoto, Y. Angew. Chem. Int. Ed.2005,44,5526. (c) Yanada, R.; Obika, S.; Kono, H.; Takemoto, Y. Angew. Chem. Int. Ed.2006,45,3822. (d) Asa.; Iso, K.; Yudha S., S. Org. Lett.2006,8, 4149. (e) Mori, S.; Uerdingen, M.; Krause, N.; Morokuma, K. Angew. Chem. Int. Ed.2005,44,4715. (f) Asao, N.; Chan, C. S.; Takahashi, K.; Yamamoto, Y. Tetrahedron 2005,61,11322. (g) Ohtaka, M.; Nakamura, H.; Yamamoto, Y. Tetrahedron Lett.2004,45,7339. (h) Witulski, B.; Alayrac, C.; Tevzadze-Saeftel, L. Angew. Chem. Int. Ed.2003,42,4257.
26. (a) Huang, Q.; Larock, R. C. J. Org. Chem.2003,68,980. (b) Dai, G.; Larock, R. C. J. Org. Chem.2003,68,920. (c) Dai, G.; Larock, R. C. J. Org. Chem.2002,67, 7042. (d) Huang, Q.; Hunter, J. A.; Larock, R. C. J. Org. Chem.2002,67,3437. (e) Roesch, K. R.; Larock, R. C. J. Org. Chem.2002,67,86. (f) Roesch, K. R.; Larock, R. C.J. Org. Chem.2001,66,8042. (g) Roesch, K. R.; Larock, R. C. Org. Lett.1999,1,553. (h) Roy, S.; Roy, S., Neuenswander B.; Hill, D.; Larock R. C J. Comb. Chem.2009,11,1061.
27. For selected examples, see:(a) Patil, N. T.; Mutyala, A. K.; Lakshmi, Pediredla G. V. V.; Raju, Penmatcha V. K.; Sridhar, B. Eur. J. Org. Chem.2010,10,1999. (b) Alfonsi, M.; Dell'Acqua, M.; Facoetti, D.; Arcadi, A.; Abbiati, G.; Rossi, E. Eur. J. Org. Chem.2009,2852. (c) Dyker, G.; Stirner, W.; Henkel, G. Eur. J. Org. Chem.2000,1433. (d) Asao, N.; Iso, K.; Yudha S, S. Org. Lett.2006,8,4149. (e) Huang, Q.; Hunter, J. A.; Larock, R. C. Org. Lett.2001,3,2973.
28. (a) Gao. K.; Wu, J. J. Org. Chem.2007,15,8611. (b) Ding, Q.; Wu, J. Org. Lett. 2007,9,4959. (c) Ye. Y.; Ding, Q.; Wu, J. Tetrahedron 2008,64,1378. (d) Yu, X.; Wu. J. J. Comb. Chem.2009,11,895.
29. (a) Yu, X.; Chen, Z.; Yang, X.; Wu, J. J. Comb. Chem.2010,12,374. (b) Chen, Z.; Yang, X.; Wu, J. Chem. Commun.2009,3469. (c) Chen, Z.; Su, M.; Yu, X.; Wu, J. Org. Biomol. Chem.2009,7,4641. (d) Ye, S.; Yang, X.; Wu, J. Chem. Commun. 2010,46,5238. (e) Chen, Z.; Yu, X.; Su, M.; Yang, X.; Wu, J. Adv. Synth. Catal. 2009,351,1692.
30. Fujito, H.; Tominaga, Y.; Matsuda, Y.; Kobayashi, G. Heterocycles 1977,6,379.
31. (a) Yoshinori, T.; Yuchi, I.; Tomoko, M.; Chizuko, K.; Akira, H. J. Heterocyclic Chem.1990,27,263. (b) Yoshinori, T.; Yuchi, I.; Akira, H. Heterocycles 1988,27, 2345. (c) Potts, K.; Youzwak, H.; Zurawel, S. Jr. J. Org. Chem.1980,45,90.
32. For selected examples, see:(a) Yu, X.; Wu, J. J. Comb. Chem.2009,11,895. (b) Ye, S.; Yang, X.; Wu, J. Chem. Comm.2010,46,5238. (c) Ding, Q.; Wu, J. Org. Lett.2007,9,4959. (d) Gao, K.; Wu, J. J. Org. Chem.2007,72,8611. (e) Sun, W.; Ding, Q.; Sun, X.; Fan, R.; Wu, J. J. Comb. Chem.2007,9,690. (f) Chen, Z.; Yu, X.; Su, M.; Yang, X.; Wu, J. Adv. Synth. Catal.2009,351,1692. (g) Chen, Z.; Yang, X.; Wu, J. Chem. Commun,2009,3469.
33. Ding, Q.; Chen, Z.; Yu, X.; Peng, Y.; Wu, J. Tetrahedron Lett.2009,50,340.
34. Hoffmann, R. W. Dehydrobenzene and Cycloalkynes; Academic:New York, 1967.
35. (a) Heaney, H. Chem. Rev.1961,62,81. (b) Kessar, S. V. Acc. Chem. Res.1978, 11,283. (c) Bryce, M. R.; Vernon, J. M. Advances in Heterocyclic Chemistry, KAtritsky, A. R., Boulton, A. J., Eds.; Academic:New York,1981; 28,183. (d) Buchwald, S. L.; Nielsen, R. B. Chem. Rev.1988,88,1047. (e) Snieckus, V. Chem. Rev.1990,90,879. (f) Majoral, J. P.; Igaul, A.; Cadierno, V.; Zablocka, M. Top. Curr. Chem.2002,220,54. (g) Pellissier, H.; Santelli, M. Tetrahedron 2003, 59,701. (h) Jia, G. Ace. Chem. Res.2004,37,479. (i) Guitian, E.; Perez, D.; Pena, D. Top Organomet. Chem.2005,14,109.
36. (a) Pellissier, H.; Santelli, M. Tetrahedron 2003,59,701. (b) Satindevr, K. E. Ace. Chem. Res.1978,11,283. (c) Jia, G. Ace. Chem. Res.2004,37,479. (d) Buchwald, S. L.; Nielsen, R. B. Chem. Rev.1988,88,1047. (e) Heaney, H. Chem. Rev.1961,62,81. (f) Wenk, H. H.; Winkler, M.; Sander, W. Angew. Chem. Int. Ed.2003,42,502. (g) Gilchrist, T. L. In The Chemistry of Functional Groups Supplement C; Patai, S.; Rappoport, Z., Eds.; Wiley:Chichester,1983,383. (h) Hart, H. In The Chemistry of Triple-bonded Funcional Groups Supplement C2; Patai, S., Ed.; Wiley:New York,1994; 1017.
37. (a) Friedman, L.; Logullo, F. M. J. Am. Chem. Soc.1963,85,1549. (b) Logullo, F. M.; Seitz, A. H.; Friedman, L. Org. Synth.1968,48,12. (c) Buxton, P. C.; Fensome. M.; Heaney, H.; Mason, K. G. Tetrahedron 1995,51,2959.
38. Himeshinma, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett.1983,1211.
39. Wu, Q.; Li, B.; Shi, C.; Chen, Y. Chinese Journal of Synthetic Chemistry 2007,15, 111.
40. (a) Kitamura, T.; Yamane, M. Chem. Commun.1995,983. (b) Kitamura, T.; Yamane, M.; Inoue, K.; Todaka, M.; Fukatsu, N.; Meng, Z.; Fujiwara, Y. J. Am. Chem.Soc.1999,121,11674.
41. Dong, C.; Hu, Q. Org. Lett.2006,8,5057.
42. Ganta, A.; Snowden, T. S. Synlett 2007,14,2227.
43. Gomez, B.; Guitian, E.; Castedo, L. Synlett 1992,903.
44. Hosoya, T.; Hamura, T.; Kuriyama, Y.; Miyamoto, M.; Matsumoto, T.; Suzuki, K. Synlett 2000,520.
45. Kurita, J.; Kakusawa, N.; Yasuike, S.; Tsuchiya, T. Heterocycles 1990,31,1937.
46. Khanapure, S. P.; Bhawal, B. M.; Biehl, E. R. Heterocycles 1991,32,1773.
47. (a) Yeom, H.; Kim, S.; Shin, S. Synlett 2008,924. (b) Ding, Q.; Wu, J. Adv. Synth. Catal.2008,350,1850.
48. (a) Coskun, N.; Tuncman, S. Tetrahedron 2006,62,1345. (b) Ding, Q.; Wang, Z.; Wu, J. J. Org. Chem.2009,74,921.