Citation: Hu Huayou, Li Guodong, Gu Ning, Ji Min. Synthesis of 3-Unsubstituted Indolizines from Electron Deficient Alkenes under Transition Metal Free Conditions[J]. Chinese Journal of Organic Chemistry, ;2016, 36(2): 330-335. doi: 10.6023/cjoc201509044 shu

Synthesis of 3-Unsubstituted Indolizines from Electron Deficient Alkenes under Transition Metal Free Conditions

Hu Huayou ^a,b ,
Li Guodong ^b ,
Gu Ning ^a ,
Ji Min ^a

1.
a School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096;
2.
b School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300

Received Date: 30 September 2015
Available Online: 26 October 2015
Fund Project: 国家自然科学基金(No. 21202058) (No. 21202058)江苏省高校重大(No. 13KJA150001) (No. 13KJA150001)中国博士后基金(Nos. 2012M511645, 2013T60483)资助项目 (Nos. 2012M511645, 2013T60483)

3-Unsubstituted indolizine not only exhibits a variety of important biological activities, but also is a kind of important intermediate in organic synthesis. A transition metal free method for synthesizing 3-unsubstituted indolizines from pyridines, 2-chloroacetic acid and electron deficient alkenes has been invented in this paper. The designed products were obtained via oxidative dehydrogenation and decarboxylation reactions, and 2,2,6,6-tetramthyl-1-piperidinyloxy (TEMPO) was used as an oxidant. This method featured simple procedure, easy available starting materials and transition metal free conditions.
- indolizine,
- 2,2,6,6-tetramthyl-1-piperidinyloxy,
- 1,3-dipolar cycloaddition,
- transition metal free reaction,
- dehydroaromatization
1. [1]
  [1] (a) Wang B.; Zhang C.-F. Chin. Wild Plant Resour. 2009, 28, 6 (in Chinese). (王冰, 张朝凤, 中国野生植物资源, 2009, 28, 6.) (b) Ewing, J.; Hughes, G. K.; Ritchie, E. W.; Taylor, C. Nature 1952, 169, 618. (c) Flitsch, W. In Comprehensive Heterocyclic Chemistry, Vol. 4, Eds.: Katritzki, A. R.; Rees, C. W., Pergamon, Oxford, 1984. (d) Swinbourne, F. T.; Hunt, J.; Klinkert, K. In Advances in Heterocyclic Chemistry, Vol. 23, Eds.: Katritzki, A. R.; Boulton, A. J., Academic Press, New York, 1978. (e) Reimann, E. Prog. Chem. Org. Nat. Prod. 2007, 88, 1. (f) Michael, J. P. Nat. Prod. Rep. 2008, 25, 139. (g) Michael, J. P. Nat. Prod. Rep. 2003, 20, 458; (h) Snyder, S. A.; ElSohly, A. M.; Kontes, F. Angew. Chem., Int. Ed. 2010, 49, 9693.
2. [2]
  [2] (a) Hagishita, S.; Yamada, M.; Shirahase, K.; Okada, T.; Murakami, Y.; Ito, Y.; Matsuura, T.; Wada, M.; Kato, T.; Ueno, M.; Chikazawa, Y.; Yamada, K.; Ono, T.; Teshirogi, I.; Ohtani, M. J. Med. Chem. 1996, 39, 3636. (b) Ghosh, A. K.; Bilcer, G.; Schiltz, G. Synthesis 2001, 2203. (c) List, B.; Castello, C. Synlett 2001, 1687. (d) Sonnet, P.; Dallemagne, P.; Guillon, J.; Enguehard, C.; Stiebing, S.; Tanguy, J.; Bureau, R.; Rault, S.; Auvray, P.; Moslemi, S.; Sourdaine, P.; Seralini, G. E. Bioorg. Med. Chem. Lett. 2000, 8, 945. (e) Maryanoff, B. E.; Vaught, J. L.; Shank, R. P.; McComsey, D. F.; Costanzo, M. J.; Nortey, S. O. J. Med. Chem. 1990, 33, 2793. (f) Lillelund, V. H.; Jensen, H. H.; Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515. (g) Liao Z.-Y.; Zhang W.-N.; You L.; Guo W.; Zhang J.; Sheng C.-Q.; Yao J.-Z.; Shan X.-Y.; Wang W.-Y. Chin. J. Med. Chem. 2008, 18, 105 (in Chinese). (缪震元, 张万年, 游亮, 郭巍, 张晶, 盛春泉, 姚建忠, 车晓颖, 王文雅, 中国药物化学杂志, 2008, 18, 105.)
3. [3]
  [3] (a) Vlahovici, A.; Andrei, M.; Druta, I. J. Lumin. 2002, 96, 279. (b) Vlahovici, A.; Druta, I.; Andrei, M.; Cotlet, M.; Dinica, R. J. Lumin. 1999, 82, 155. (c) Mitsumori, T.; Bendikov, M.; Dautel, O.; Wudl, F.; Shioya, T.; Sato, H.; Sato, Y. J. Am. Chem. Soc. 2004, 126, 16793. (d) Saeva, F. D.; Luss, H. R. J. Org. Chem. 1988, 53, 1804. (e) Sonnenschein, H.; Henrich, G.; Resch-Genger, U.; Schulz, B. Dyes Pigm. 2000, 46, 23. (f) Retaru, A. V.; Druta, L. D.; Deser, T.; Mueller, T. J. Helv. Chim. Acta 2005, 88, 1798. (g) Delattre, F.; Woisel, P.; Surpateanu, G.; Cazier, F.; Blach, P. Tetrahedron 2005, 61, 3939. (h) Mitsumori, T.; Campos, L. M.; Garcia-Garibay, M. A.; Wudl, F.; Sato, H.; Sato, Y. J. Mater. Chem. 2009, 19, 5826.
4. [4]
  [4] Selected examples: (a) Park, C.; Ryabova, V.; Seregin, I. V.; Sromek, A. W.; Gevorgyan, V. Org. Lett. 2004, 6, 1159. (b) Seregin, I. V.; Ryabova, V.; Gevorgyan, V. J. Am. Chem. Soc. 2007, 129, 7742. (c) Chernyak, N.; Tilly, D.; Li, Z.; Gevorgyan, V. ARKIVOC 2011, 76. (d) Liégault, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou, K. J. Org. Chem. 2009, 74, 1826. (e) Lapointe, D.; Fagnou, K. Org. Lett. 2009, 11, 4160. (f) Xia, J.; Wang, X.; You, S. J. Org. Chem. 2009, 74, 456. (g) Yang, Y.; Cheng, K.; Zhang, Y. Org. Lett. 2009, 11, 5606. (h) Yang, Y.; Chen, L.; Zhang, Z.; Zhang, Y. Org. Lett. 2011, 13, 1342. (i) Liu, B.; Qin, X.; Li, K.; Li, X.; Guo, Q.; Lan, J.; You, J. Chem. Eur. J. 2010, 16, 11836. (j) Huang, Y.; Song, F.; Wang, Z.; Xi, P.; Wu, N.; Wang, Z.; Lan, J.; You, J. Chem. Commun. 2012, 48, 2864. (k) Liu, B.; Wang, Z.; Wu, N.; Li, M.; You, J.; Lan, J. Chem. Eur. J. 2012, 18, 1599. (l) Ma, Y.; You, J.; Song, F. Chem. Eur. J. 2013, 19, 1189. (m) Zhao, B. Org. Biomol. Chem. 2012, 10, 7108. (n) Hu, H.; Liu, Y.; Zhong, H.; Zhu, Y.; Wang, C.; Ji, M. Chem. Asian J. 2012, 7, 884. (o) Hu, H.; Liu, Y.; Xu, J.; Kan, Y.; Wang, C.; Ji, M. RSC Adv. 2014, 4, 24389. (p) Hu, H.; Li, G.; Hu, W.; Liu, Y.; Wang, X.; Kan, Y.; Ji, M. Org. Lett. 2015, 17, 1114.
5. [5]
  [5] (a) Dawood, K. M.; Ragab, E. A.; Khedr, N. A. J. Chin. Chem. Soc. (Taipei, Taiwan) 2009, 56, 1180. (b) Darwish, E. S. Molecules 2008, 13, 1066. (c) Kheder, N. A.; Darwish, E. S.; Dawood, K. M. Heterocycles 2009, 78, 177. (d) Shen, Y.-M.; Wang, B.-X.; Feng, Y.-Y.; Shen, Z.-Y.; Shen, J.; Li, C.; Hu, H.-W. Chem. J. Chin. Univ. 2006, 27, 651 (in Chinese). (沈永淼, 王炳祥, 冯玉英, 沈珠英, 沈健, 胡宏纹, 高等学校化学学报, 2006, 27, 651.) (e) Wang, B.-X.; Hu, H.-W. Chem. J. Chin. Univ. 2004, 25, 273 (in Chinese). (王炳祥, 胡宏纹, 高等学校化学学报, 2004, 25, 273.) (f) Tanaka, A.; Usui, T. Chem. Pharm. Bull. 1979, 27, 3078. (g) Tominaga, Y.; Hidaki, S.; Matsuda, Y.; Kobayashi, G.; Sakemi, K. Yakugaku Zasshi 1979, 99, 540. (h) Hu, H.; Feng, J.; Zhu, Y.; Gu, N.; Kan, Y. RSC Adv. 2012, 2, 8637. (i) Wang, C.; Hu, H.; Xu, J.; Kan, W. RSC Adv. 2015, 5, 41255.
6. [6]
  [6] Zhang, L.; Liang, F.; Sun, L.; Hu, Y.; Hu, H. Synthesis 2000, 1733.
7. [7]
  [7] (a) Liu, Y.; Hu, H.; Zhang, Y.; Hu, H.; Xu, J. Org. Biomol. Chem. 2010, 8, 4921. (b) Hu, H.; Shi, K.; Hou, R.; Zhang, Z.; Zhu, Y.; Zhou, J. Synthesis 2010, 4007. (c) Hu, H.; Ma, K. Crystallogr. Rep. 2010, 55, 1211.
8. [8]
  [8] (d) Liu, Y.; Hu, H.; Su, X.; Sun, J.; Cao, C.; Shi, Y. Eur. J. Org. Chem. 2013, 2020. (e) Sun, J.; Wang, F.; Hu, H.; Wang, X.; Wu, H.; Liu, Y. J. Org. Chem. 2014, 79, 3992. (f) Li, G.; Hu, H.; Kan, Y.; Ma, K. Chin. J. Org. Chem. 2014, 34, 903 (in Chinese). (李国栋, 胡华友, 阚玉和, 马奎蓉, 有机化学, 2014, 34, 903.) (g) Wang, F.; Shen, Y.; Hu, H.; Wang, X.; Wu, H.; Liu, Y. J. Org. Chem. 2014, 79, 9556. (h) Sun, J.; Hu, H.; Wang, F.; Wu, H.; Liu, Y. RSC Adv. 2014, 4, 36498.
9. [9]
  [9] Selctcted reviews for TEMPO as oxidant or catalyst for oxidation: (a) Mallat, T.; Baiker, A. Chem. Rev. 2004, 104, 3037. (b) Wertz, S.; Studer, A. Green Chem. 2013, 15, 3116. (c) Campbell, A. N.; Stahl, S. S. Acc. Chem. Res. 2012, 45, 851. (d) Schultz, M. J.; Sigman, M. S. Tetrahedron 2006, 62, 8227. (e) Zhan, B.; Thompson, A. Tetrahedron 2004, 60, 2917. (f) Murarka, S.; Wertz, S.; Studer, A. Chimia 2012, 66, 413.
10. [10]
  [10] Shi, F.; Zhang, Y.; Lu, Z.; Zhu, X.; Kan, W.; Wang, X.; Hu, H. Synthesis 2016, 48, 413.
11. [11]
  [11] Shibuya, M.; Tomizawa, M.; Iwabuchi, Y. J. Org. Chem. 2008, 73, 4750
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