摘要
本论文主要围绕金催化的不对称加成反应展开。
在第一部分工作中,以共轭烯炔酮和硝酮为底物,实现了金催化下的不对称[3+3]环加成反应。以高区域选择性和高对映选择性获得了一系列呋喃并噁唑啉环的双环类化合物。通过研究发现：对于手性配体MeO-biphep的修饰,无论是改变配体中与磷相连基团的大小或者改变配体的二面角都可以获得优秀的结果。大部分的产物能以高区域选择性、高产率以及高对映选择性得到。该反应所用的手性配体(R)-Cn-tunephos(n=1-3)也是首次应用于金化学。反应可以放大到5mmol的量,以大于20：1的区域选择性,93%的对映选择性和几乎定量的产率得到产物,产物在钯碳催化下能进行氮氧键的选择性断裂得到氨基醇类化合物。
第二部分工作中,以Y-醇-丁炔酸酯的缩醛(酮)衍生物和芳香醛为底物。在温和的反应条件下,以较高的收率和优秀的对映选择性实现了在金催化下的[3+2]的不对称环加成反应,得到了一类功能化的4-烷氧基2,5-二氢呋喃类化合物。在研究该不对称环加成反应时,设计合成了一系列手性亚磷酰胺配体以满足不同底物的要求。在这部分工作中对于不同的底物引入了三种不同的手性配体,以优良的收率和高的对映选择性得到了4-烷氧基2,5-二氢呋喃类化合物,这类化合物作为一个结构单元在天然产物和药物分子中广泛存在。同时,将该反应的量放大到5mmol,反应能以良好的收率和优秀的对映选择性得到产物,该方法为合成这类砌块提供了一种简单有效的可能途径。通过引入光学纯的底物,我们对反应进行的机理进行了研究,反应可能是经过一个全碳1,3-偶极子的中间体参与的反应机理。
The main work of the thesis is around gold-catalyzed asymmetric cycloaddition reactions, which is devided into two parts and is listed as follows:
In the first part, gold-catalyzed asymmetric [3+3] cycloaddition reactions of conjugated eneyne ketones with nitrones are discussed. A series of furan and oxazoline bicyclic fused compounds were obtained with high yield, high diastereo selectivity and high enantioselectivity. It is found that excellent results can be achived by modification substituted groups connecting to phosphorus or changing the dugedrak angle of chiral ligand MeO-biphep.The catalyst loading could be reduced to0.2mol%without any loss in the yield, diastereoselectivity and enantioselectivity on-a5mmol scale reaction.The adduct could undergo further chemoselective transformation to give the isolated optically active multi-functionalized furan in good yield without loss of ee from the Pd/C-catalyzed hydrogenation.
The second part focuses on the gold-catlayzed asymmetric [3+2] cycloaddition reactions of y-alcohol-butyne acid ester acetal with aromatic aldehydes (ketones) derivatives. The reactions gave a class of functional4-alkoxy2,5-dihydrofuran, a key unit in some natural products and drug molecules, with high yields and excellent enantioselectivites under mild conditions. In the same time, a series of phosphoramide ligands, which were designed and synthesized, have been successfully used in the reaction. Like in the case of the first part, catalyst loading could be reduced to1mol%with a larger reaction scale (5mmol) without loss of any selectivity and efficiency to provide the product. This method provides a simple and effective route to synthesis this kind of compounds. By introducing the optical pure substrate, the reaction mechanism was also investigated, which indicated that a all-carbon1,3-dipole was involved in the reaction.
引文
1. Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc.1986,108,6405.
2. Togni, A.; Pastor, S. D. J. Org. Chem.1990,55,1649.
3. Hughes, P. F.; Smith, S. H.; Olson, J. T. J. Org. Che.1994,59,5799.
4. Reviews for gold-catalyzed asymmetric reactions:(a) Lee, A-L. Annu, Rep, Prog.Chem. Sect. B,2011,107,369; (b) Corma, A.; Leyva-Perez. A.; Sabater, M. J. Chem. Rev.2011,111.1657; (c) Aubert. C.:Fensterbank. L.; Garcia, P.; Malacria, M.; Simonneau. A. Chem. Rev.2011. 111,1954:(d) Krause. N.; Winter, C. Chem. Rev.2011. 111,1994:(e) Rudolph. M.;Hashmi, A. S. K. Chem. Soc. Rev. 2012,41,2448; (f) Marinetti, A.; Jullien. H.; Voituriez, A. Chem. Soc. Rev.2012, 41,4884; (g) Sengupta, S.; Shi, X. ChemCatChem 2010,2.609; (h) Loh, C. C. J.; Enders, D. Chem. Eur. J.2012,18,10212; (i) Rudolph, M; Hashmi, A. S. K. Chem. Commun.2011,47,6536; (j) Garayalde, D.; Nevado, C. ACS Catal 2012, 2,1462.
5. (a) Knowles, W, S.; Sabacky, M. J. J. Chem. Soc. Chem. Commun.1968,1445; (b) Horner, L.; Siegel, H.; Biithe, H. Angew. Chem., Int. Ed. Engl.1968,7,942.
6. (a) Knowles, W, S.; Sabacky, M. J. J. Chem. Soc. Chem. Commun.1968,1445; (b) Horner, L.; Siegel, H.; Biithe, H. Angew. Chem., Int. Ed. Engl.1968,7,942.
7. Miyashita, A.; Yasuda, A.; Takay, H.; Toriumi, H.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc.1980,102,7932.
8. Munoz, M. P.; Adrio, J.; Carretero, J. C.; Echavarren, A. M. Organometallics 2005,24,1293.
9. Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc.2005, 127,18002.
10. Watson, I. D. G.; Ritter, S.; Toste, F. D. J. Am. Chem. Soc.2009,131,2056.
11. Uemura, M.; Watson, I. D. G.; Katsukawa, M. Toste, F. D. J. Am. Chem. Soc. 2009,131,3464.
12. Chao, C. M.; Beltrami, D.; Toullec, P. Y.; Michelet, V. Chem. Commun.2009, 6988.
13. (a) Chao, C. M.; Vitale, M. R.; Toullec, P. Y.; Genet, J. P.; Michelet, V. Chem. Eur. J.2009,15,1319; (b) Pradal, A.; Chao, C. M.; Vitale, M. R.; Toullec, P. Y.; Michelet, V. Tetrahedron 2011,67,4731.
14. Briones, J. F.; Davies, H. M. L. J. Am. Chem. Soc.2012,134,11916.
15. Martinez, A.; Garcia-Garcia, P.; Fernandez-Rodriguez, M. A. Rodriguez, F.; Sanz, R. Anew. Chem., Int. Ed.2010,49,4633.
16. Brazeau, J. F.; Zhang, S.; Colomer,I.; Corkey. B. K.; Toste, F. D. J. Am. Chem. Soc.2012,134,2742.
17. Gawade, S. A.; Bhunia, S.; Liu. R. S. Angeu:Chem.. Int. Ed.2012.51,7835.
18. Tarselli, M. A.; Chianese. A. R.;Lee. S. J.;Gagne, M, R. Angew. Chem., Int. Ed. 2007,46,6670.
19. Luzung, M. R.;Mauleon. P. Toste. F. D. J. Am. Chem. Soc.2007,129,12402.
20. Liu, C.;Widenhofer, R. A. Org. Lett.2007.9.1935.
21. Sethofer, S. G.;Mayer, T.;Toste, F. D. J. Am. Chem. Soc.2010,132,8276.
22. Cera, G.; Chiarucci, M.; Mazzanti. A.; Mancinelli, M.; Bandini, M. Org. Lett. 2012,14,1350.
23. Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc.2009,131,9178.
24. Gampbell, M, J.; Toste, F. D. Chem. Sci.2011,2,1369.
25. (a) Zhou, G.; Liu, F.; Zhang, J. Chem.-Eur. J.2011,17,1301; (b) Zhang, Y.; Zhang, J. Chem. Commun.2012,48,4710.
26. LaLonde, R. L.; Sherry, B. D.; Kang, E. J.; Toste, F. D. J. Am. Chem. Soc.2007, 129,2452.
27. Zhang, Z.; Bender, C. F.; Widenhoefer, R. A. Org. Lett,2007,9,2887.
28. Zhang, Z.; Bender, C. F.; Wodenhoefer, R. A. J. Am. Chem. Soc.2007,129,14148.
29. Zhang, Z.; Lee, S. U.; Wodenhoefer, R. A. J. Am. Chem. Soc.2009,131,5373.
30. Kanno, O.; Kuriyama, W.; Wang, Z. J.; Toste, F. D. Angew. Chem., Int. Ed.2011, 50,9919.
31. Rodriguez, L. I.; Roth, T.; Fillol, J. L.; Wadepohl, H.; Gade, L. H. Chem,-Eur. J. 2012,18,3721.
32. Butler, K. L.; Tragni, M.; Widenhoefer. Angew. Chem., Int. Ed. 2012,51,5157.
33. Bandini, M.; Eichholzer, A. Angew. Chem., Int. Ed.2009,48,9533.
34. Bandini, M.; Monari, M.; Romaniello, A.; Tragni, M.; Chem.-Eur. J.2010,16, 14272.
35. (a) Lu. Z.; Ma. S. Angew. Chem., Int. Ed.2008,47,258; (b) Trost, B. M. Zhang, T.; Sieber. J. D. Chem. Sci.2010,1,427; (c) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003,103.2921.
36. Mukherjee, P.:Widenhoefer. R. A. Angew. Chem., Int. Ed.2012,57,1405.
37. Kojima. M.; Mikami. K. Chem.-Eur. J.2011,17,13950.
38. (a) Stanley. L. M.:Sibi. M. P. Chem. Rev.2008,108,2887; (b) Pandey, G.; Banerjee. P.; Gadre. S. R. Chem. Rev.2006.106,4484.
39. (a) Melhado. A. D.; Luparia. M.:Toste. D. F. J. Am. Chem. Soc.2007,129,12638; (b) Melhado. A. D.; Amarante. G. W.; Wang. A. J.; Luparia, M.; Toste, F. D. J. Am. Chem. Soc.2011.733.3517.
40. (a) Martin-Rodrfguez. M.:Najera. C.; Sansano, J. M.; Wu. F. L. Tetrahedron: Asymmetry 2010,27,1184; (b) Martin-Rodriguez, M.; Najera, C.; Sansano, J. M.; Cozar, A.; Cossio, F. P. Chem.-Eur. J.2011,17,14224.
41. Padilla, S.; Adrio, J.; Carretero, J. C. J. Org. Chem.2012,77,4161.
42. (a) Hulst, R.; De Vires. N. K.; Feringa, B. L. Tetrahedron:Asymmetry 1994,5, 699; (b) De Vires, A. H. M.; Meetsma, A.; Feringa, B. L. Angew. Chem., Int. Ed. 1996,45, 2374.
43. (a) Feringa, B. L.; Teichert, J. F. Angew. Chem., Int. Ed.2010,49,2486; (b) Minnaard, A. J.; Feringa, B. L.; Lefort, L.; De Vires, J. G. Ace. Chem. Res.2007. 40,1267; (c) Feringa, B. L. Acc. Chem. Res.2000,33,346.
44. (a) Alonso, I.; Trillo, B.; Lopez, F.; Montserrat, S.; Ujaque, G.; Castedo, L.; Lledos, A.; Mascarenas, J. L. J. Am. Chem. Soc.2009,131,13020; (b) Alonso, I.; Faustino, H.; Lopez, F.; Mascarenas, J. L. Angew. Chem. Int. Ed.2011,50,11496.
45. Gonzalez, A. Z.; Toste, F. D. Org. lett,2010,12,200.
46. Gonzalez, A. Z.; Benitez, D.; Tkatchouk, E.; Goddard Ⅲ, W. A.; Toste, F. D. J. Am. Chem. Soc.2011,133,5500.
47. (a) Teller, H.; Flgge, S.; Goddard, R.; Fiirstner, A. Angew. Chem., Int. Ed.2010, 49,1949; (b)Teller, H.; Furstner, A. Chem.-Em. J.2011.17,7764; (c) Teller, H.; Corbet, M.; Mantilli, L.; Gopakumar, G:Goddard. R.; Thiel. W.:Furstner, A. J. Am. Chem. Soc.2012,134,15331. (d) Liu. B.:Li. K.-N.:Luo. S.-W.; Huang, J.-Z.; Pang, H.; Gong, L.-Z. J. Am. Chem. Soc.203.135,3323.
48. (a) Wanzlick, H. W.; Schonherr. H. J. Angew:Chem.. Int. Ed. Engl.1968,7,141; (b) Ofele, K. J. Organomet. Chem.1968.72.42.
49. Arduengo, A. J. Ⅲ.;Harlow. R. L:Kline. M. J. Am. Chem. Soc.1991.113,361.
50. (a) Herrmann. W. A:kocher. C. Angew. Chem. Int., Ed.1997,36.2162; (b) Herrmann. W. A. Angew. Chem. Int. Ed.2002,41,1290; (c) Diez-Gonzalez, S.: Marion. N.; Nolan. S. P. Chem. Rev.2009,109,3612; (d) Nolan, S. P. Acc. Chem. Res,2011,44.91.
51. (a) Enders. D.:Niemeier, O.; Hensler, A. Chem. Rev.2007,107,5606; (b) Marion, N.; Diez-Gonzalez. S.; Nolan, S. P. Angew. Chem., Int. Ed.2007,46,2988.
52. Corbera, R.; Ramirez, J.; Poyatos, M.; Peris, E.; Fernandez, E. Tetrahedron: Asymmetry 2006,17,1759.
53. Matsumoto, Y.; Selim, K. B.; Nakanishi, H.; Yamada, K.; Yamamoto, Y.; Tomikoa, K. Tetrahedron Lett.2010,51,404.
54. Aartolome, C.; Garcia-Cuadrado, D.; Ramiro, Z.; Espinet, P. Inor. Chem.2010? 49, 9758.
55. Wang, Y. M.; Kuzniewski, C. N. Rauniyer, V.; Hoogn, C.; Toste, F. D. J. Am. Chem. Soc.2011,133,12972
56. Handa, S.; Slaughter, L. G. M. Angew. Chem., Int. Ed.2012,51,2912.
57. Wang, W.; Li, T.; Mulburn, R.; Yates, J.; Hinnant, E.; Luzzio, M. J.; Noble, S. A.; Attardo, G. Bioorg. Med. Chem. Lett.1998,8,1953.
58. (a) Wang, W.; Yang, J.; Wang, F.; Shi, M. Organometallics 2011,20,3859; (b) Yang, J.; Zhang, R.; Wang, W.; Zhang, Z.; Shi, M. Tetrahedron:Asymmetry 2011, 22,2029.
59. (a) Wikclens, K.; Lentz, D.; Czekelius, C. Organometallics 2011,30,1287; (b) Mourad, A. K.; Leutzow, J.; Czekelius, C. Angew. Chem., Int. Ed.2012,50, 11149.
60. Francos, J.; Grande-Carmona, F.; Faustino, H.; Iglesias-Sigiienza, J.; Diez, E.; Alonso, I.; Fernandez, R.; Lassaletta. J. M.; Lopez, F.; Mascarenas, J. L. J. Am. Chem. Soc.2012,134,14322.
61. (a) Hamilton, G. L.; Kang, E. J.; Mba. M.:Toste, F. D. Science 2007,317,496; (b) Lacour, J.; Linder, D. Science 2007,317.462; (c) Aikawa, K.; Kojima, M.; Mikami, K. Angew. Chem., Int. Ed.2009,48,6073; (d) LaLonde, R. L.; Wang. Z. J.; Mba, M.;Lackner, A. D.; Toste, F. D. Angew. Chem., Int. Ed.2010.49.598; (e) Kjimaa, M.; Mikami. K. Synlett 2012.57; Phipps. R. J.:Hamilton. G., L.;Toste, F. D. Nat. Chem.2012,4,603.
1. Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc.2004,126,11164.
2. For recent reviews of furan synthesis, see:Hou, X. L.; Yang, Z.; Yeung, K. S.; Wong, H. N. C, in Progress in Heterocyclic Chemistry,2008,19, P.176。
3. Patil, N. T.; Wu, H.; Yamamoto, Y. J. Org. Chem.2005,70,4531.
4. Oh, C. H.; Reddy, V. R.; Kim, A.; Rhim, C., Y. Tetrahedron Lett.2006,47,5307
5. Liu, Y.; Zhou, S. Org. Lett.2005,6,4609.
6. Yao, T.; Zhang, X.; Larock. R. C. J. Org. Chem.2005,70,7679.
7. Xiao, Y.; Zhang, J. Angew. Chem., Int. Ed.2008,47,1903.
8. (a) Yu, X.; Ren, H.; Xiao. Y.; Zhang, J. Chem.-Eur. J.2008.14,8481:(b) Xiao. Y.; Zhang, J. Chem. Commun.2009,3594.
9. Liu. F.;Qian. D.;Li. L.;Zhao. X.;Zhang. J. Angew. Chem.. Int. Ed.2009.48, 5505.
10. Zhang, Y.;Liu. F.; Zhang. J. Chem.-Eur. J.2010.16.6146.
11. (a) Gao, H.; Zhao. X.; Zhang. J. Chem.-Eur J.2010.16.456:(b) Gao. H.; Wu, X.; Zhang, J. Chem.-Eur. J.2011, H.2838:(c) Gao. H.; Wu. X.; Zhang. J. Chem. Commun.2010,46,8764.
12. Zhang, Z.; Qian, H.; Longmire, J.; Zhang, X. J. Org. Chem.2000,65,6223.
13. (a) LaLonde, R. L.; Sherry, B. D.; Kang, E. J.; Toste, F. D. J. Am. Chem. Soc. 2007,129,2452; (b) Aikawa, K.; Kojima, M.; Mikami, K. Adv. Synth. Catal 2010,352,3131.
14.(a)高洪银,华东师范大学博士学位论文 2011：(b)于秀招,华东师范大学 博士学位论文 2012。
15.(a)Evan,D.A.;Song,H-J.;Fandrick,K.R.Org.Lett.2006,8,3351；(b)Tian,L.; Xu,G.-Y.;Ye,Y.;Liu,L.-Z.Synthesis.2003,1329.
16.(a)Seriazwa,M.;Fujinami,S.;Ukaji,Y.;Inomata,K.Tetrahedron Asymmetric. 2008,19,921；(1)Aschwanden,P.;Kvrn,L.;Geisser,R.W.;Klernbeck,F.; Carreira,E.M.Org.Lett.2005,7,5741.
1. For selected examples on transition-metal-catalyzed cycloaddition reactions, see: (a) P. A. Evans, J. E. Robinson, E. W. Baum, A. N. Fazal, J. Am. Chem. Soc.2002, 124,8782; b) P. A. Wender, G G. Gamber, R. D. Hubbard, S. M. Pham, L. Zhang, J. Am. Chem. Soc.2005,127,2836; (c) P. R. Chopade, J. Louie, Adv. Synth. Catal 2006,348,2307; (d) B. Heller, M. Hapke, Chem. Soc. Rev.2007,36,1085; (e) M. Rubin, M. Rubina, V. Gevorgyan, Chem. Rev.2007,107,3117; (f) Z. X. Yu, Y. Wang, Y. Y. Wang, Chem. Asia. J.2010,5,1072.
2. (a) Uchida, I.; Takase, S.; Hayakiri, H.; Kiyoto, S.; Hashimoto, M.; Tada, T.; Koda, S.; Morimoto, Y.; J. Am. Chem. Soc.1987,109,4108; (b) Terano, H.; Takase, S.; Hosoda, J.; Kohsaka, M.; J. Antibiot.1989,43,145; (c) Yu, Q.-S.; Zhu, X.; Holloway, H.W.; Whittaker,N. F.; Brossi, A.; Greig,N. H. J. Med. Chem.2002,45, 3684; (d) Katoh, T.; Itoh, E.; Yoshino, T.; Terashima, S. Tetrahedron 1997,53, 10229; (e) Judd, T. C.; Williams, R. M. Angew. Chem. Int. Ed.2002,41,4683; (f) Suzuki, M.; Kambe, M.; Tokuyama, H.; Fukuyama,T. Angew. Chem. Int. Ed. 2002,41,4686.
3. For reviews on nitrone chemistry, see:(a) Martin, J. N.; Jones, R. C. F. In Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products; Padwa, A., Pearson, W. H., Eds.; Wiley and Sons:Hoboken, NJ,2003; Chapter 1, p 1; (b) Cardona,F.; Goti, A. Angew. Chem. Int. Ed.2005,44,7832; (c) Liu, F.; Qian, D.; Li, L.; Zhao, X.; Zhang, J. Angew. Chem. Int. Ed.2010,49,6669. (d) Kissane, M.; Maguire, A. R. Chem. Soc. Rev. 2010,39,845
4. (a) Hudlicky, T.; Reed, J. W. Angew. Chem. Int. Ed.2010,49,4864; (b) Clemens, R. T.; Jennings, M. P. Chem. Commun.,2006,2720; (c) Brichacek, M.; Njardarson, J. T. Org. Biomol. Chem.,2009,7,1761; () Kang, B.; Chang, S.; Decker, S.; Britton, R. Org. Lett.2010,12,1716; () Liu, J-F.; Jiang, Z-Y.; Wang, R-R.; Zheng, Y-T.; Chen, J-J.; Zhang, X-M.; Ma, Y-B. Org. Lett.2007,9,4127
5. (a) Coulson, D. R. Inorg. Synth.1971,13,121; (b) Zhang, G.; Zhang, L.;J. Am. Chem. Soc.2008,130,12598.
6. Chen, Y.; Yekta, S.; Yudin, A. K. Chem. Rev.2003,103,3155.
7. Alexakis, A.; Gille, S.; Prian, F.; Rosset, S.; Ditrich, K. Tetrahedron Lett.2004,45, 1449.
8. (a) Feringa, B. L.; Teichert, J. F. Angew. Chem., Int. Ed.2010,49,2486; (b) Minnaard, A. J.; Feringa, B. L.; Lefort, L.; De Vires, J. G. Acc. Chem. Res.2007, 40,1267; (c) Feringa, B. L. Acc. Chem. Res.2000,33,346; (d) Harada, H.; Thalji, R. K.; Bergman, R. G.; Ellman, J. A. J. Org. Chem.2008,73,6772; (e) Arnold, L. A.; Imbos, R.; Mandoli, A.; de Vriew, A. H. M.; Naasz, R.; Feringa, B. L. Tetrahedron 2000,56,2865; (f) Polet, D.; Alexakis, A. Org. Lett.2005,7,1621.