亚甲胺叶立德与环丙基亚甲基乙酸乙酯参与的催化不对称exo-1,3-偶极环加成反应构建5-氮杂-螺[2,4]庚烷片段
收稿日期: 2014-04-03
网络出版日期: 2014-04-21
基金资助
项目受973计划（No.2011CB808600）、国家自然科学基金（No.21172176）与湖北省青年人才基金（No.ZRZ0273）资助.
Catalytic Asymmetric exo-Selective 1,3-Dipolar Cycloaddition of Azomethine Ylides and Ethyl Cyclopropylidene Acetate for Construction of 5-aza-Spiro[2,4]heptane Motif
Received date: 2014-04-03
Online published: 2014-04-21
Supported by
Project supported by National Basic Research Program of China (973 Program) (No. 2011CB808600), the National Natural Science Foundation of China (No. 21172176) and Hubei Province NSF (No. ZRZ0273).
首次研究了Cu（CH3CN）4BF4/DTBM-BIPHEP催化的亚甲胺叶立德与环丙基亚甲基乙酸乙酯参与的不对称1，3-偶极环加成反应，获得了优异的exo-选择性，研究结果证实大空间位阻的手性双膦配体对反应的非对映选择性控制起到至关重要的影响；同时一步高效构建三个叔碳手性中心和一个螺环季碳中心. 该不对称1，3-偶极环加成反应收率良好，得到优秀的非对映（>98：2，dr）与对映选择性（ee值高达99%）. 该催化体系为合成exo构型的5-氮杂-螺[2，4]庚烷衍生物提供了一种简洁高效的方法，具有原子经济性好、反应条件温和、底物适用范围广等优点.
关键词： 不对称催化; 1,3-偶极环加成; 亚甲胺叶立德; 环丙基亚甲基乙酸乙酯; 5-氮杂-螺[2,4]庚烷
李清华 , 黄蓉 , 王春江 . 亚甲胺叶立德与环丙基亚甲基乙酸乙酯参与的催化不对称exo-1,3-偶极环加成反应构建5-氮杂-螺[2,4]庚烷片段[J]. 化学学报, 2014 , 72(7) : 830 -835 . DOI: 10.6023/A14040249
A direct and facile access to highly functionalized 5-aza-spiro[2,4]heptane derivatives is developed via Cu(CH3CN)4BF4/DTBM-BIPHEP-catalyzed asymmetric exo-selective 1,3-dipolar cycloaddition of azomethine ylides with ethyl cyclopropylidene acetate for the first time. The Cu(CH3CN)4BF4/DTBM-BIPHEP complex was identified as the optimal catalyst for the exo-selectivity. The reaction was carried out smoothly with wide substrate scope, and electron-deficient, electron-neutral and electron-rich aryl substituted imino esters were all compatible with the reaction, affording the 5-aza-spiro[2,4]heptane adducts containing three tertiary stereogenic centers and one spiro quaternary center in moderate to good yield (53%～83%) with excellent diastereoselectivity (>98:2, dr) and high enantioselectivity (up to 99% ee). The less reactive alkyl substituted imino ester derived from butyraldehyde was also tolerated in this annulation. The absolute configuration of the cycloadduct was unequivocally determined to be (4R,6S,7S) by X-ray analysis of N-tosylated derivative of exo-3a. Based on the relative and absolute configuration of the exo-cycloadducts, we proposed that an exo approach of ethyl 2-cyclopropylidene acetate to the copper(I) complex occurred predominantly because of the disfavored steric repulsion generated in the endo approach between the substituents of ethyl 2-cyclopropylidene acetate and the large bulky aryl group on the phosphorus atom of the chiral ligand. The produced 5-aza-spiro[2,4]heptanes fragment is widely present in many bioactive carbapenems derivatives, HSR-903 and substituted oxazolidinones. The optically active compounds with different stereoselectivities show different biological activities, therefore, it is important to develop the atom economical method for the asymmetric synthesis ofbiologically active exo-selective 5-aza-spiro[2,4]heptane derivatives.
[1] Zhu, S.-F.; Zhou, Q.-L. in Privileged Chiral Ligands and Catalysts Ed.: Zhou, Q.-L., Wiley-VCH, Weiheim, 2011, pp. 137～170.
[2] (a) Bindra, J. S. in The Alkaloids,Vol. 14, Ed.: Manske, R. H. F., Academic Press, New York, 1973; for reviews, see:
(b) Galliford, C. V.; Scheidt, K. A. Angew. Chem., Int. Ed. 2007, 46, 8748;
(c) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2209;
(d) Kang, T. H.; Matsumoto, K.; Murakami, Y.; Takayama, H.; Kitajima, M.; Aimi, N.; Watanabe, H. Eur. J. Pharmacol. 2002, 444, 39;
(e) Ma, J.; Hecht, S. M. Chem. Commun. 2004, 1190;
(f) Edmondson, S.; Danishefsky, S. J.; Sepp-Lorenzino, L.; Rosen, N. J. Am. Chem. Soc. 1999, 121, 2147;
(g) Lee, K. K.; Zhou, B.-N.; Kingston, D. G. I.; Vaisberg, A. J.; Hammond, G. B. Planta Med. 1999, 65, 759;
(h) Raj, A. A.; Raghunathan, R.; SrideviKumari, M. R.; Raman, N. Bioorg. Med. Chem. 2003, 11, 407.
[3] (a) Becker, M. H.; Chua, P.; Downham, R.; Douglas, C. J.; Garg, N. K.; Hiebert, S.; Jaroch, S.; Matsuoka, R. T.; Middleton, J. A.; Ng, F. W.; Overman, L. E. J. Am. Chem. Soc. 2007, 129, 11987;
(b) Sun, M. R.; Lu, H. T.; Wang, Y. Z.; Yang, H.; Liu, H. M. J. Org. Chem. 2009, 74, 2213;
(c) Shangary, S.; Qin, D.; McEachern, D.; Liu, M.; Miller, R. S.; Qiu, S.; Nikolovska-Coleska, Z.; Ding, K.; Wang, G.; Chen, J.; Bernard, D.; Zhang, J.; Lu, Y.; Gu, Q.; Shah, R. B.; Pienta, K. J.; Ling, X.; Kang, S.; Guo, M.; Sun, Y.; Yang, D.; Wang, S. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 3933;
(d) Cui, C. B.; Kakeya, H.; Osada, H. J. Antibiot. 1996, 49, 832;
(e) Park, H. B.; Jo, N. H.; Hong, J. H.; Chei, J. H.; Cho, J.-H.; Yoo, K. H.; Oh, C.-H. Arch. Pharm. Chem. Life Sci. 2007, 340, 530;
(f) Cianchetta, G.; Mannhold, R.; Cruciani, G.; Baroni, M.; Cecchetti, V. J. Med. Chem. 2004, 47, 3193.
[4] (a) Pietruszka, J. Chem. Rev. 2003, 103, 1051;
(b) Wessjohann, L. A.; Brandt, W.; Thiemann, T. Chem. Rev. 2003, 103, 1625;
(c) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem. Rev. 2003, 103, 1213.
[5] For recent reviews, see: (a) Shi, M.; Shao, L.-X.; Lu, J.-M.; Wei, Y.; Mizuno, K.; Maeda, H. Chem. Rev. 2010, 110, 5883;
(b) Pellisier, H. Tetrahedron 2010, 66, 8341;
(c) Galano, A.; Alvarez-Idaboy, J.; Vivier-Bunge, A. Theor. Chem. Acc. 2007, 118, 597; for some recent examples, see:
(d) Komagawa, S.; Takeuchi, K.; Sotome, I.; Azumaya, I.; Masu, H.; Yamasaki, R.; Saito, S. J. Org. Chem. 2009, 74, 3323;
(e) Fukusaki, Y.; Miyazaki, J.; Azumaya, I.; Katagiri, K.; Komagawa, S.; Yamasaki, R.; Saito, S. Tetrahedron 2009, 65, 10631;
(f) Yamasaki, R.; Sotome, I.; Komagawa, S.; Azumaya, I.; Masu, H.; Saito, S. Tetrahedron Lett. 2009, 50, 1143;
(g) Pohlhaus, P. D.; Sanders, S. D.; Parsons, A. T.; Li, W.; Johnson, J. S. J. Am. Chem. Soc. 2008, 130, 8642;
(h) Jackson, S. K.; Karadeolian, A.; Driega, A. B.; Kerr, M. A. J. Am. Chem. Soc. 2008, 130, 4196;
(i) Bajtos, B.; Yu, M.; Zhao, H.; Pagenkopf, B. L. J. Am. Chem. Soc. 2007, 129, 9631;
(j) Perreault, C.; Goudreau, S. R.; Zimmer, L. E.; Charette, A. B. Org. Lett. 2008, 10, 689;
(k) Saito, S.; Komagawa, S.; Azumaya, I.; Masuda, M. J. Org. Chem. 2007, 72, 9114;
(l) Saito, S.; Takeuchi, K. Tetrahedron Lett. 2007, 48, 595;
(m) Maeda, K.; Saito, S. Tetrahedron Lett. 2007, 48, 3173;
(n) Shi, M.; Liu, L. P.; Tang, J. J. Am. Chem. Soc. 2006, 128, 7430;
(o) Komagawa, S.; Saito, S. Angew. Chem., Int. Ed. 2006, 45, 2446;
(p) Saito, S.; Masuda, M.; Komagawa, S. J. Am. Chem. Soc. 2004, 126, 10540;
(q) Young, I. S.; Kerr, M. A. Angew. Chem., Int. Ed. 2003, 42, 3023;
(r) Kawasaki, T.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2002, 67, 4911;
(s) Pisaneschi, F.; Piacenti, M.; Cordero, F. M.; Brandi, A. Tetrahedron: Asymmetry 2006, 17, 292.
[6] Pisaneschi, F.; Piacenti, M.; Cordero, F. M.; Brandi, A. Tetrahedron: Asymmetry 2006, 17, 292.
[7] Henderson, J. R.; Parvez, M.; Keay, B. A. Org. Lett. 2007, 9, 5167.
[8] Kuethe, J. T.; Zhao, D. L.; Humphrey, G. R.; Journet, M.; McKeown, A. E. J. Org. Chem. 2006, 71, 2192.
[9] Liu, T.-L.; He, Z.-L.; Tao, H.-Y.; Cai, Y.-P.; Wang, C.-J. Chem. Commun. 2011, 47, 2616.
[10] Lin, G.-Q.; Sun, X.-W.; Chen, Y.-Q.; Li, Y.-M.; Chen, X.-Z. Chiral Synthesis——Principles and Application of Asymmetric Reaction, Science Press, Beijing, 2013. (林国强, 孙兴文, 陈耀全, 李月明, 陈新滋, 手性合成——不对称反应及其应用, 科学出版社, 北京, 2013.)
[11] For recent reviews about 1,3-dipolar cycloaddition reactions of azomethine ylides, see: (a) Engels, B.; Christl, M. Angew. Chem. Int. Ed. 2009, 48, 7968;
(b) Stanley, L. M.; Sibi, M. P. Chem. Rev. 2008, 108, 2887;
(c) Alvarez-Corral, M.; Munoz-Dorado, M.; Rodríguez-García, I. Chem. Rev. 2008, 108, 3174;
(d) Bonin, M.; Chauveau, A.; Micouin, L. Synlett 2006, 2349;
(e) Nájera, C.; Sansano, J. M. Angew. Chem., Int. Ed. 2005, 44, 6272;
(f) Adrio, J.; Carretero, J. C. Chem. Commun. 2011, 47, 6784; for recent examples, see:
(g) Chen, X.-H.; Zhang, W.-Q.; Gong, L.-Z. J. Am. Chem. Soc. 2008, 130, 5652;
(h) Chen, X.-H.; Wei, Q.; Luo, S.-W.; Xiao, H.; Gong, L.-Z. J. Am. Chem. Soc. 2009, 131, 13819;
(i) He, L.; Chen, X.-H.; Wang, D.-N.; Luo, S.-W.; Zhang, W.-Q.; Yu, J.; Ren, L.; Gong, L.-Z. J. Am. Chem. Soc. 2011, 133, 13504;
(j) Guo, C.; Song, J.; Gong, L.-Z. Org. Lett. 2013, 15, 2676;
(k) Zeng, W.; Chen, G.-Y.; Zhou, Y.-G.; Li, Y.-X. J. Am. Chem. Soc. 2007, 129, 750;
(l) Zeng, W.; Zhou, Y.-G. Org. Lett. 2005, 7, 5055;
(m) Zeng, W.; Zhou, Y.-G. Tetrahedron Lett. 2007, 48, 4619;
(n) Yu, S.-B.; Hu, X.-P.; Deng, J.; Wang, D.-Y.; Duan, Z.-C.; Zheng, Z. Tetrahedron: Asymmetry 2009, 20, 621;
(o) Longmire, J. M.; Wang, B.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 13400;
(p) Yan, X.-X.; Peng, Q.; Zhang, Y.; Zhang, K.; Hong, W.; Hou, X.-L.; Wu, Y.-D. Angew. Chem., Int. Ed. 2006, 45, 1979;
(q) Shi, J.-W.; Zhao, M.-X.; Lei, Z.-Y.; Shi, M. J. Org. Chem. 2008, 73, 305;
(r) Wang, L.; Shi, X.-M.; Dong, W.-P.; Zhu, L.-P.; Wang, R. Chem. Commun. 2013, 49, 3458;
(s) Wua, H.; Wang, B.; Liu, H.; Wang, L. Tetrahedron 2011,67, 1210.
[12] (a) Wang, C.-J.; Liang, G.; Xue, Z.-Y.; Gao, F. J. Am. Chem. Soc. 2008, 130, 17250;
(b) Wang, C.-J.; Xue, Z.-Y.; Liang, G.; Lu, Z. Chem. Commun. 2009, 2905;
(c) Liang, G.; Tong, M.-C.; Wang, C.-J. Adv. Synth. Catal. 2009, 351, 3101;
(d) Xue, Z.-Y.; Liu, T.-L.;Lu, Z.; Huang, H.; Tao, H.-Y.; Wang, C.-J. Chem. Commun. 2010, 46, 1727;
(e) Liang, G.; Tong, M.-C.; Tao, H.-Y.; Wang, C.-J. Adv. Synth. Catal. 2010, 352, 1851;
(f) Liu, T.-L.; Xue, Z.-Y.; Tao, H.-Y.; Wang, C.-J. Org. Biomol. Chem. 2011, 9, 1980;
(g) Xue, Z.-Y.; Fang, X.; Wang, C.-J. Org. Biomol. Chem. 2011, 9, 3622;
(h) Liu, T.-L.; He, Z.-L.; Tao, H.-Y.; Wang, C.-J. Chem. Eur. J. 2012, 18, 8042;
(i) Li, Q.-H.; Tong, M.-C.; Li, J.; Tao, H.-Y.; Wang, C.-J. Chem. Commun. 2011, 47, 11110;
(j) Liu, T.-L.; He, Z.-L.; Wang, C.-J. Chem. Commun. 2011, 47, 9600;
(k) Teng, H.-L.; Huang, H.; Tao, H.-Y.; Wang, C.-J. Chem. Commun. 2011, 47, 5494;
(l) Teng, H.-L.; Luo, F.-L.; Tao, H.-Y.; Wang, C.-J. Org. Lett. 2011, 13, 5600;
(m) Liu, T.-L.; He, Z.-L.; Li, Q.-H.; Tao, H.-Y.; Wang, C.-J. Adv. Synth. Catal. 2011, 353, 1713;
(n) Tong, M.-C.; Li, J.; Tao, H.-Y.; Li, Y.-X.; Wang, C.-J. Chem. Eur. J. 2011, 17, 12922;
(o) Yan, D.; Li, Q.; Wang, C.-J. Chin. J. Chem. 2012, 30, 2714;
(p) Liu, T.-L.; He, Z.-L.; Tao, H.-Y.; Wang, C.-J. Chem. Eur. J. 2012, 18, 8042;
(q) Teng, H.-L.; Huang, H.; Wang, C.-J. Chem. Eur. J. 2012, 18, 16214;
(r) Liu, K.; Teng, H.-L.; Yao, L.; Tao, H.-Y.; Wang, C.-J. Org. Lett. 2013, 15, 2250;
(s) He, Z.-L.; Teng, H.-L.; Wang, C.-J. Angew. Chem., Int. Ed. 2013, 52, 2934; (t) Tong, M.-C.; Chen, X.; Tao, H.-Y.; Wang, C.-J. Angew. Chem., Int. Ed. 2013, 52, 12377; (u) Teng, H.-L.; Yao, L.; Wang, C.-J. J. Am. Chem. Soc. 2014, 136, 4075.
[13] Li, Q.-H.; Xue, Z.-Y.; Tao, H.-Y.; Wang, C.-J. Tetrahedron Lett. 2012, 53, 3650.
[14] Li, Q.-H.; Liu, T.-L.; Wei, L.; Zhou, X.; Tao, H.-Y.; Wang, C.-J. Chem. Commun. 2013, 49, 9642.
/
| 〈 |
|
〉 |
