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]
  Hong Lu , Yidie Zhai , Xingxing Cheng , Yujia Gao , Qing Wei , Hao Wei . Advancements and Expansions in the Proline-Catalyzed Asymmetric Aldol Reaction. University Chemistry, 2024, 39(5): 154-162. doi: 10.3866/PKU.DXHX202310074
2. [2]
  Tingyu Zhu , Hui Zhang , Wenwei Zhang . Exploration and Practice of Ideological and Political Education in the Course of Experiments on Chemical Functional Molecules: Synthesis and Catalytic Performance Study of Chiral Mn(III)Cl-Salen Complex. University Chemistry, 2024, 39(4): 75-80. doi: 10.3866/PKU.DXHX202311011
3. [3]
  Yongqing Kuang , Jie Liu , Jianjun Feng , Wen Yang , Shuanglian Cai , Ling Shi . Experimental Design for the Two-Step Synthesis of Paracetamol from 4-Hydroxyacetophenone. University Chemistry, 2024, 39(8): 331-337. doi: 10.12461/PKU.DXHX202403012
4. [4]
  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
5. [5]
  Yue Zhao , Yanfei Li , Tao Xiong . Copper Hydride-Catalyzed Nucleophilic Additions of Unsaturated Hydrocarbons to Aldehydes and Ketones. University Chemistry, 2024, 39(4): 280-285. doi: 10.3866/PKU.DXHX202309001
6. [6]
  Guojie Xu , Fang Yu , Yunxia Wang , Meng Sun . Introduction to Metal-Catalyzed β-Carbon Elimination Reaction of Cyclopropenones. University Chemistry, 2024, 39(8): 169-173. doi: 10.3866/PKU.DXHX202401060
7. [7]
  Ke Li , Chuang Liu , Jingping Li , Guohong Wang , Kai Wang . 钛酸铋/氮化碳无机有机复合S型异质结纯水光催化产过氧化氢. Acta Physico-Chimica Sinica, 2024, 40(11): 2403009-. doi: 10.3866/PKU.WHXB202403009
8. [8]
  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
9. [9]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
10. [10]
  Yurong Tang , Yunren Shi , Yi Xu , Bo Qin , Yanqin Xu , Yunfei Cai . Innovative Experiment and Course Transformation Practice of Visible-Light-Mediated Photocatalytic Synthesis of Isoquinolinone. University Chemistry, 2024, 39(5): 296-306. doi: 10.3866/PKU.DXHX202311087
11. [11]
  Houjin Li , Wenjian Lan . Name Reactions in University Organic Chemistry Laboratory. University Chemistry, 2024, 39(4): 268-279. doi: 10.3866/PKU.DXHX202310016
12. [12]
  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
13. [13]
  Aiai WANG , Lu ZHAO , Yunfeng BAI , Feng FENG . Research progress of bimetallic organic framework in tumor diagnosis and treatment. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1825-1839. doi: 10.11862/CJIC.20240225
14. [14]
  Feng Sha , Xinyan Wu , Ping Hu , Wenqing Zhang , Xiaoyang Luan , Yunfei Ma . Design of Course Ideology and Politics for the Comprehensive Organic Synthesis Experiment of Benzocaine. University Chemistry, 2024, 39(2): 110-115. doi: 10.3866/PKU.DXHX202307082
15. [15]
  Xinyu Zhu , Meili Pang . Application of Functional Group Addition Strategy in Organic Synthesis. University Chemistry, 2024, 39(3): 218-230. doi: 10.3866/PKU.DXHX202308106
16. [16]
  Tianyun Chen , Ruilin Xiao , Xinsheng Gu , Yunyi Shao , Qiujun Lu . Synthesis, Crystal Structure, and Mechanoluminescence Properties of Lanthanide-Based Organometallic Complexes. University Chemistry, 2024, 39(5): 363-370. doi: 10.3866/PKU.DXHX202312017
17. [17]
  Shicheng Yan . Experimental Teaching Design for the Integration of Scientific Research and Teaching: A Case Study on Organic Electrooxidation. University Chemistry, 2024, 39(11): 350-358. doi: 10.12461/PKU.DXHX202408036
18. [18]
  Yong Wang , Yingying Zhao , Boshun Wan . Analysis of Organic Questions in the 37th Chinese Chemistry Olympiad (Preliminary). University Chemistry, 2024, 39(11): 406-416. doi: 10.12461/PKU.DXHX202403009
19. [19]
  Heng Zhang . Determination of All Rate Constants in the Enzyme Catalyzed Reactions Based on Michaelis-Menten Mechanism. University Chemistry, 2024, 39(4): 395-400. doi: 10.3866/PKU.DXHX202310047
20. [20]
  Zhuoming Liang , Ming Chen , Zhiwen Zheng , Kai Chen . Multidimensional Studies on Ketone-Enol Tautomerism of 1,3-Diketones By ¹H NMR. University Chemistry, 2024, 39(7): 361-367. doi: 10.3866/PKU.DXHX202311029

Get Citation

PDF

XML

Metrics

PDF Downloads(6)
Abstract views(1159)
HTML views(176)

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