Citation: Shi Minglin, Zhan Gu, Du Wei, Chen Yingchun. Direct Asymmetric Aza-Vinylogous Mannich Reaction of Nitrones from Isatins and Ketimines[J]. Acta Chimica Sinica, ;2017, 75(10): 998-1002. doi: 10.6023/A17060277 shu

Direct Asymmetric Aza-Vinylogous Mannich Reaction of Nitrones from Isatins and Ketimines

West China School of Pharmacy, Sichuan University, Chengdu 610041, China

Corresponding author: Du Wei, duweiyb@scu.edu.cn Chen Yingchun, ycchen@scu.edu.cn
Received Date: 26 June 2017
Available Online: 31 October 2017
Fund Project: the National Natural Science Foundation of China 21602143Project supported by the National Natural Science Foundation of China (No. 21602143)

Figures(2)

Direct asymmetric vinylogous Mannich reaction is an efficient and powerful method for the synthesis of δ-amino-α, β-unsaturated carbonyl compounds; however, the nucleophiles are generally limited to γ-butenolides and α, α-dicyanoolefins. Therefore, it is highly desirable to design new vinylogous nucleophiles and develop the related asymmetric reactions. Recently, we disclosed a new type of nitrones derived from isatins and N-benzyl hydroxylamines, which could easily generate nitrone ylide species in the presence of a tertiary amine, and undergo asymmetric formal[3+2] cycloadditions with α, β-unsaturated aldehydes via iminium ion catalysis of a chiral secondary amine. Subsequently, we found that such nitrone ylides could isomerize to more interesting aza-dienolate-type intermediates, and engage in direct stereoselective aza-vinylogous Michael reactions with nitroalkenes under the catalysis of a bifunctional thiourea-tertiary amine, delivering chiral nitrone derivatives with extended carbon skeletons without subsequent cyclization. In this case, the same type of nitrones are employed as nucleophilic precursors under the catalysis of a cinchona alkaloid-based thiourea substance, and effectively assembled with isatins-derived ketimines to accomplish the direct asymmetric aza-vinylogous-type Mannich reactions. A series of densely functionalized nitrones with vicinal tertiary-quaternary stereogenic centers are furnished in high yields (70%~97%) with good to excellent stereoselectivity (83%~99% ee, >19:1 dr). Moreover, subsequent[3+2] dipolar cycloaddition reactions between the chiral nitrones and activated alkenes can be realized in exclusive diastereoselectivity, producing complex spirocyclic indolenine architectures incorporating a hydrogenated isoxazole ring. These nitrones, as a new type of aza-vinylogous nucleophiles, may have a wide range of applications in asymmetric synthesis in the future. A representative procedure for the asymmetric aza-vinylogous-type Mannich reaction is as follows:nitrone 1 (0.1 mmol), ketimine 2 (0.11 mmol), catalyst C5 (0.01 or 0.02 mmol) are added into an oven-dried vial equipped with a magnetic stirbar. Xylene (1.0 mL) is added and the mixture is stirred at 50℃ and monitored by TLC. After completion, the residue is purified by flash column chromatography on silica gel eluting with petroleum ether/ethyl acetate (15:1 to 5:1) to afford the product 3.
- asymmetric catalysis,
- organocatalysis,
- vinylogous Mannich reaction,
- nitrones,
- ketimines
1. [1]
  (a) Schneider, C.; Sickert, M. In Chiral Amine Synthesis, Ed.:Nugent, T. C., Wiley-VCH, Weinheim, 2010.
  (b) Roselló, M. S.; del Pozo, C.; Fustero, S. Synthesis 2016, 48, 2553.
  (c) Martin, S. F. Acc. Chem. Res. 2002, 35, 895.
2. [2]
  (a) Yamaguchi, A.; Matsunaga, S.; Shibasaki, M. Org. Lett. 2008, 10, 2319.
  (b) Shepherd, N. E.; Tanabe, H.; Xu, Y.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2010, 132, 3666.
  (c) Zhou, L.; Lin, L.; Ji, J.; Xie, M.; Liu, X.; Feng, X. Org. Lett. 2011, 13, 3056.
  (d) Guo, Y.-L.; Bai, J.-F.; Peng, L.; Wang, L.-L.; Jia, L.-N.; Luo, X.-Y.; Tian, F.; Xu, X.-Y.; Wang, L.-X. J. Org. Chem. 2012, 77, 8338.
  (e) Yin, L.; Takada, H.; Kumagai, N.; Shibasaki, M. Angew. Chem. Int. Ed. 2013, 125, 7451.
  (f) Guo, Y.; Zhang, Y.; Qi, L.; Tian, F.; Wang, L. RSC Adv. 2014, 4, 27286.
  (g) Nakamura, S.; Yamaji, R.; Hayashi, M. Chem. Eur. J. 2015, 21, 9615.
3. [3]
  (a) Liu, T.-Y.; Cui, H.-L.; Long, J.; Li, B.-J.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. J. Am. Chem. Soc. 2007, 129, 1878.
  (b) Niess, B.; Jϕrgensen, K. A. Chem. Commun. 2007, 1620.
  (c) Chen, Q.-A.; Zeng, W.; Wang, D.-W.; Zhou, Y.-G. Synlett 2009, 2009, 2236.
  (d) Xiong, X.-F.; Jia, Z.-J.; Du, W.; Jiang, K.; Liu, T.-Y.; Chen, Y.-C. Chem. Commun. 2009, 6994.
  (e) Cheng, C.; Lu, X.; Ge, L.; Chen, J.; Cao, W.; Wu, X.; Zhao, G. Org. Chem. Front. 2017, 4, 101.
4. [4]
  Zhang, H.-J.; Shi, C.-Y.; Zhong, F.; Yin, L. J. Am. Chem. Soc. 2017, 139, 2196. doi: 10.1021/jacs.6b13042
5. [5]
  (a) Curti, C.; Rassu, G.; Zambrano, V.; Pinna, L.; Pelosi, G.; Sartori, A.; Battistini, L.; Zanardi, F.; Casiraghi, G. Angew. Chem. Int. Ed. 2012, 51, 6200.
  (b) Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.; Sartori, A.; Pelosi, G.; Zanardi, F.; Casiraghi, G. Adv. Synth. Catal. 2013, 355, 1881.
  (c) Chen, Q.; Wang, G.; Jiang, X.; Xu, Z.; Lin, L.; Wang, R. Org. Lett. 2014, 16, 1394.
  (d) Ranieri, B.; Sartori, A.; Curti, C.; Battistini, L.; Rassu, G.; Pelosi, G.; Casiraghi, G.; Zanardi, F. Org. Lett. 2014, 16, 932.
  (e) Di Iorio, N.; Righi, P.; Ranieri, S.; Mazzanti, A.; Margutta, R. G.; Bencivenni, G. J. Org. Chem. 2015, 80, 7158.
  (f) Xiao, X.; Mei, H.; Chen, Q.; Zhao, X.; Lin, L.; Liu, X.; Feng, X. Chem. Commun. 2015, 51, 580.
  (g) Zheng, C.; Chen, W.-X.; Chen, F.-E. Asian J. Org. Chem. 2015, 4, 1044.
  (h) Han, J.-L.; Chang, C.-H. Chem. Commun. 2016, 52, 2322.
  (i) Tian, L.; Hu, X.-Q.; Li, Y.-H.; Xu, P.-F. Chem. Commun. 2013, 49, 7213.
  (j) Sun, Q.; Li, X.; Su, J.; Zhao, L.; Ma, M.; Zhu, Y.; Zhao, Y.; Zhu, R.; Yan, W.; Wang, K.; Wang, R. Adv. Synth. Catal. 2015, 357, 3187.
  (k) Li, X.; Su, J.; Liu, Z.; Zhu, Y.; Dong, Z.; Qiu, S.; Wang, J.; Lin, L.; Shen, Z.; Yan, W.; Wang, K.; Wang, R. Org. Lett. 2016, 18, 956.
6. [6]
  Liu, Y.; Yang, Y.; Huang, Y.; Xu, X.-H.; Qing, F.-L. Synlett 2015, 26, 67.
7. [7]
  (a) Chen, Y.-R.; Zhan, G.; Du, W.; Chen, Y.-C. Adv. Synth. Catal. 2016, 358, 3759. For other examples with nitrone ylides, see:
  (b) Hanessian, S.; Bayrakdarian, M. Tetrahedron Lett. 2002, 43, 967.
  (c) Hanessian, S.; Bayrakdarian, M. Tetrahedron Lett. 2002, 43, 9441.
  (d) Merino, P.; Tejero, T.; Díez-Martínez, A.; Gültekin, Z. Eur. J. Org. Chem. 2011, 2011, 6567.
  (e) Merino, P.; Tejero, T.; Díez-Martínez, A. J. Org. Chem. 2014, 79, 2189.
  (f) Juste-Navarro, V.; Delso, L.; Tejero, T.; Merino, P. Chem. Eur. J. 2016, 22, 11527.
  (g) Prieto, L.; Juste-Navarro, V.; Uria, U.; Delso, I.; Reyes, E.; Tejero, T.; Carrillo, L.; Merino, P.; Vicario, J. L. Chem. Eur. J. 2017, 23, 2764.
8. [8]
  Zhan, G.; Shi, M.-L.; Lin, W.-J.; Ouyang, Q.; Du, W.; Chen, Y.-C. Chem. Eur. J. 2017, 23, 6286. doi: 10.1002/chem.201701290
9. [9]
  For selected examples, see:(a) Feng, J.; Yan, W.; Wang, D.; Li, P.; Sun, Q.; Wang, R. Chem. Commun. 2012, 48, 8003.
  (b) Hara, N.; Nakamura, S.; Sano, M.; Tamura, R.; Funahashi, Y.; Shibata, N. Chem. Eur. J. 2012, 18, 9276.
  (c) Yan, W.; Wang, D.; Feng, J.; Li, P.; Zhao, D.; Wang, R. Org. Lett. 2012, 14, 2512.
  (d) Zhao, J.; Fang, B.; Luo, W.; Hao, X.; Liu, X.; Lin, L.; Feng, X. Angew. Chem. Int. Ed. 2015, 54, 241.
  (e) Wang, Y.; Cao, Z.; Niu, Y.; Zhao, X.; Zhou, J. Acta Chim. Sinica 2014, 72, 867. (王雨卉, 曹中艳, 牛艳霏, 赵小莉, 周剑, 化学学报, 2014, 72, 867.)
  (f) Liu, Y.-L.; Zhou, J. Chem. Commun. 2013, 49, 4421.
  (g) Yin, X.; Xue, P.; Dong, K.; Liao, K.; Zhou, F.; Zhou, J. Acta Chim. Sinica 2015, 73, 685. (尹小平, 徐鹏巍, 董坤, 廖奎, 周锋, 周剑, 化学学报, 2015, 73, 685.)
10. [10]
  (a) Li, B.-J.; Jiang, L.; Liu, M.; Chen, Y.-C.; Ding, L.-S.; Wu, Y. Synlett 2005, 603.
  (b) Connon, S. J. Chem. Commun. 2008, 2499.
  (c) Takemoto, Y. Chem. Pharm. Bull. 2010, 58, 593.
  (d) Taylor, M. S.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2006, 45, 1520.
11. [11]
  CCDC-1558319(4) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
1. [1]
  Wenxiu Yang , Jinfeng Zhang , Quanlong Xu , Yun Yang , Lijie Zhang . Bimetallic AuCu Alloy Decorated Covalent Organic Frameworks for Efficient Photocatalytic Hydrogen Production. Acta Physico-Chimica Sinica, 2024, 40(10): 2312014-. doi: 10.3866/PKU.WHXB202312014
2. [2]
  Yingchun ZHANG , Yiwei SHI , Ruijie YANG , Xin WANG , Zhiguo SONG , Min WANG . Dual ligands manganese complexes based on benzene sulfonic acid and 2, 2′-bipyridine: Structure and catalytic properties and mechanism in Mannich reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1501-1510. doi: 10.11862/CJIC.20240078
3. [3]
  Peiran ZHAO , Yuqian LIU , Cheng HE , Chunying DUAN . A functionalized Eu³⁺ metal-organic framework for selective fluorescent detection of pyrene. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 713-724. doi: 10.11862/CJIC.20230355
4. [4]
  Tiantian MA , Sumei LI , Chengyu ZHANG , Lu XU , Yiyan BAI , Yunlong FU , Wenjuan JI , Haiying YANG . Methyl-functionalized Cd-based metal-organic framework for highly sensitive electrochemical sensing of dopamine. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 725-735. doi: 10.11862/CJIC.20230351
5. [5]
  Jingjing QING , Fan HE , Zhihui LIU , Shuaipeng HOU , Ya LIU , Yifan JIANG , Mengting TAN , Lifang HE , Fuxing ZHANG , Xiaoming ZHU . Synthesis, structure, and anticancer activity of two complexes of dimethylglyoxime organotin. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1301-1308. doi: 10.11862/CJIC.20240003
6. [6]
  Wendian XIE , Yuehua LONG , Jianyang XIE , Liqun XING , Shixiong SHE , Yan YANG , Zhihao HUANG . Preparation and ion separation performance of oligoether chains enriched covalent organic framework membrane. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1528-1536. doi: 10.11862/CJIC.20240050
7. [7]
  Zhuo WANG , Junshan ZHANG , Shaoyan YANG , Lingyan ZHOU , Yedi LI , Yuanpei LAN . Preparation and photocatalytic performance of CeO₂-reduced graphene oxide by thermal decomposition. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1708-1718. doi: 10.11862/CJIC.20240067
8. [8]
  Xingyang LI , Tianju LIU , Yang GAO , Dandan ZHANG , Yong ZHOU , Meng PAN . A superior methanol-to-propylene catalyst: Construction via synergistic regulation of pore structure and acidic property of high-silica ZSM-5 zeolite. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1279-1289. doi: 10.11862/CJIC.20240026
9. [9]
  Lu XU , Chengyu ZHANG , Wenjuan JI , Haiying YANG , Yunlong FU . Zinc metal-organic framework with high-density free carboxyl oxygen functionalized pore walls for targeted electrochemical sensing of paracetamol. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 907-918. doi: 10.11862/CJIC.20230431
10. [10]
  Xiaoling LUO , Pintian ZOU , Xiaoyan WANG , Zheng LIU , Xiangfei KONG , Qun TANG , Sheng WANG . Synthesis, crystal structures, and properties of lanthanide metal-organic frameworks based on 2, 5-dibromoterephthalic acid ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1143-1150. doi: 10.11862/CJIC.20230271
11. [11]
  Qiuyang LUO , Xiaoning TANG , Shu XIA , Junnan LIU , Xingfu YANG , Jie LEI . Application of a densely hydrophobic copper metal layer in-situ prepared with organic solvents for protecting zinc anodes. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1243-1253. doi: 10.11862/CJIC.20240110
12. [12]
  Jing SU , Bingrong LI , Yiyan BAI , Wenjuan JI , Haiying YANG , Zhefeng Fan . Highly sensitive electrochemical dopamine sensor based on a highly stable In-based metal-organic framework with amino-enriched pores. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1337-1346. doi: 10.11862/CJIC.20230414
13. [13]
  Youlin SI , Shuquan SUN , Junsong YANG , Zijun BIE , Yan CHEN , Li LUO . Synthesis and adsorption properties of Zn(Ⅱ) metal-organic framework based on 3, 3', 5, 5'-tetraimidazolyl biphenyl ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1755-1762. doi: 10.11862/CJIC.20240061
14. [14]
  Yuanpei ZHANG , Jiahong WANG , Jinming HUANG , Zhi HU . Preparation of magnetic mesoporous carbon loaded nano zero-valent iron for removal of Cr(Ⅲ) organic complexes from high-salt wastewater. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1731-1742. doi: 10.11862/CJIC.20240077
15. [15]
  Wenlong LI , Xinyu JIA , Jie LING , Mengdan MA , Anning ZHOU . Photothermal catalytic CO₂ hydrogenation over a Mg-doped In₂O_3-x catalyst. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 919-929. doi: 10.11862/CJIC.20230421
16. [16]
  Kun WANG , Wenrui LIU , Peng JIANG , Yuhang SONG , Lihua CHEN , Zhao DENG . Hierarchical hollow structured BiOBr-Pt catalysts for photocatalytic CO₂ reduction. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1270-1278. doi: 10.11862/CJIC.20240037
17. [17]
  Zhanggui DUAN , Yi PEI , Shanshan ZHENG , Zhaoyang WANG , Yongguang WANG , Junjie WANG , Yang HU , Chunxin LÜ , Wei ZHONG . Preparation of UiO-66-NH₂ supported copper catalyst and its catalytic activity on alcohol oxidation. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 496-506. doi: 10.11862/CJIC.20230317
18. [18]
  Juan WANG , Zhongqiu WANG , Qin SHANG , Guohong WANG , Jinmao LI . NiS and Pt as dual co-catalysts for the enhanced photocatalytic H₂ production activity of BaTiO₃ nanofibers. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1719-1730. doi: 10.11862/CJIC.20240102
19. [19]
  Ruolin CHENG , Haoran WANG , Jing REN , Yingying MA , Huagen LIANG . Efficient photocatalytic CO₂ cycloaddition over W₁₈O₄₉/NH₂-UiO-66 composite catalyst. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 523-532. doi: 10.11862/CJIC.20230349
20. [20]
  Yi YANG , Shuang WANG , Wendan WANG , Limiao CHEN . Photocatalytic CO₂ reduction performance of Z-scheme Ag-Cu₂O/BiVO₄ photocatalyst. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 895-906. doi: 10.11862/CJIC.20230434

Get Citation

PDF

XML

Metrics

PDF Downloads(6)
Abstract views(1137)
HTML views(172)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142