Citation: Qian Xiangyang, Xiong Peng, Xu Hai-Chao. Modular Synthesis of Functionalized 4-Quinolones via a Radical Cyclization Cascade Reaction[J]. Acta Chimica Sinica, ;2019, 77(9): 879-883. doi: 10.6023/A19050193 shu

Modular Synthesis of Functionalized 4-Quinolones via a Radical Cyclization Cascade Reaction

College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005

Corresponding author: Xu Hai-Chao, haichao.xu@xmu.edu.cn
Received Date: 25 May 2019
Available Online: 1 September 2019
Fund Project: Project supported by the National Natural Science Foundation of China (No. 21672178) and Fundamental Research Funds for the Central Universitiesthe National Natural Science Foundation of China 21672178

Figures(4)

4-Quinolones are structural motifs prevalent in natural products and biologically active compounds. However, it remains challenging to synthesize 4-quinolones that bears diverse substituents at 2-and 3-positions. Herein we report an efficient and modular method for the synthesis of 4-quinolones from easily available N-aryl-O-propargyl carbamates and CO. The reactions employ 2-iodoxybenzoic acid (IBX) as an oxidant to oxidize the N-H group of the carbamate to generate an amide radical, which undergoes radical cyclization cascade with CO to afford the 4-quinolone product. The reactions provide speedy access to a series of 2, 3-disubstituted 4-quinolones by varying the substituents of the carbamate substrate. Late stage functionalization employing Ni-catalysis allows the conversion of an OMe group on the 4-quinonone benzene ring to alkyl substituents, further increasing the diversity of the 4-quinone product. The synthetic potential is further demonstrated by running the synthesis on gram scale and by preparation of an enantiomerically enriched 4-quinolone product. The typical procedure is detailed as follows:A magnetic stirring bar, the carbamate substrate (0.25 mmol), IBX (1.0 mmol), and anhydrous dimethyl sulfoxide (DMSO, 10 mL) were placed in a 50 mL stainless steel autoclave. The autoclave was sealed, vacuumed and purged five times with CO, and finally pressurized with 10 MPa of CO. The reaction vessel was heated at 90℃ for 12 h and then cooled to r.t.. Excess CO was released in a fume hood. The reaction mixture was diluted with ethyl acetate (20 mL) and 5% NaHCO₃ (15 mL). The phases were separated. The aqueous phase was extracted with ethyl acetate (20 mL×2). The combined organic solution was washed with 5% NaHCO₃ (20 mL) and brine (20 mL). The organic solution was dried over anhydrous MgSO₄, filtered and concentrated under reduced pressure. The residue was chromatographed through silica gel eluting with ethyl acetate/hexanes to give the desired product.
- radical,
- cyclization,
- 4-quinolone,
- oxidation
1. [1]
  (a) Mitscher, L. A. Chem. Rev. 2005, 105, 559; (b) Zhanel, G. G.; Ennis K.; Vercaigne, L.; Walkty, A.; Gin, A. S.; Embil, J.; Smith, H.; Hoban1, D. J. Drugs 2002, 62, 13.
2. [2]
  (a) Nilsen, A.; Miley, G. P.; Forquer, I. P.; Mather, M. W.; Katneni, K.; Li, Y.; Pou, S.; Pershing, A. M.; Stickles, A. M.; Ryan, E.; Kelly, J. X.; Doggett, J. S.; White, K. L.; Hinrichs, D. J.; Winter, R. W.; Charman, S. A.; Zakharov, L. N.; Bathurst, I.; Burrows, J. N.; Vaidya, A. B.; Riscoe, M. K. J. Med. Chem. 2014, 57, 3818; (b) Nilsen, A.; LaCrue, A. N.; White, K. L.; Forquer, I. P.; Cross, R. M.; Marfurt, J.; Mather, M. W.; Delves, M. J.; Shackleford, D. M.; Saenz, F. E.; Morrisey, J. M.; Steuten, J.; Mutka, T.; Li, Y.; Wirjanata, G.; Ryan, E.; Duffy, S.; Kelly, J. X.; Sebayang, B. F.; Zeeman, A.-M.; Noviyanti, R.; Sinden, R. E.; Kocken, C. H. M.; Price, R. N.; Avery, V. M.; Angulo-Barturen, I.; Jiménez-Díaz, M. B.; Ferrer, S.; Herreros, E.; Sanz, L. M.; Gamo, F.-J.; Bathurst, I.; Burrows, J. N.; Siegl, P.; Guy, R. K.; Winter, R. W.; Vaidya, A. B.; Charman, S. A.; Kyle, D. E.; Manetsch, R.; Riscoe, M. K. Sci. Transl. Med. 2013, 5, 177ra137.
3. [3]
  Wang, Z. (2010). Conrad-Limpach Quinoline Synthesis. In Comprehensive Organic Name Reactions and Reagents, Z. Wang (Ed.). doi: 10.1002/9780470638859.conrr152.
4. [4]
  Gould, R. G.; Jacobs, W. A. J. Am. Chem. Soc. 1939, 61, 2890. doi: 10.1021/ja01265a088
5. [5]
  (a) Mukhina, O. A.; Kutateladze, A. G. J. Am. Chem. Soc. 2016, 138, 2110; (b) Kwon, S.; Kang, D.; Hong, S. Eur. J. Org. Chem. 2015, 2015, 3671; (c) Shao, T.; Jiang, Z. Acta Chim. Sinica 2017, 75, 70. (d) Qiang Xie, Q.; Chen, X.-J.; Huang, P.-Q. Acta Chim. Sinica 2015, 73, 705.
6. [6]
  (a) Malacria, M. Chem. Rev. 1996, 96, 289; (b) Curran, D. P. Aldrichimica Acta 2000, 33, 104.
7. [7]
  Fuentes, N.; Kong, W. Q.; Fernandez-Sanchez, L.; Merino, E.; Nevado, C. J. Am. Chem. Soc. 2015, 137, 964. doi: 10.1021/ja5115858
8. [8]
  (a) Hou, Z. W.; Mao, Z. Y.; Zhao, H. B.; Melcamu, Y. Y.; Lu, X.; Song, J.; Xu, H.-C. Angew. Chem., Int. Ed. 2016, 55, 9168; (b) Zhu, L.; Xiong, P.; Mao, Z. Y.; Wang, Y. H.; Yan, X.; Lu, X.; Xu, H.-C. Angew. Chem., Int. Ed. 2016, 55, 2226; (c) Hou, Z.-W.; Mao, Z.-Y.; Song, J.; Xu, H.-C. ACS Catal. 2017, 5810; (d) Hou, Z.-W.; Yan, H.; Song, J.-S.; Xu, H.-C. Chin. J. Chem. 2018, 36, 909; (e) Hou, Z.-W.; Mao, Z.-Y.; Melcamu, Y. Y.; Lu, X.; Xu, H.-C. Angew. Chem., Int. Ed. 2018, 57, 1636; (f) Xu, F.; Long, H.; Song, J.; Xu, H.-C. Angew. Chem., Int. Ed. 2019, 58, 9017; (g) Long, H.; Song, J. S.; Xu, H. C. Org. Chem. Front. 2018, 5, 3129; (h) Xiong, P.; Xu, H.-H.; Xu, H.-C. J. Am. Chem. Soc. 2017, 139, 2956.
9. [9]
  Nicolaou, K. C.; Baran, P. S.; Zhong, Y. L.; Barluenga, S.; Hunt, K. W.; Kranich, R.; Vega, J. A. J. Am. Chem. Soc. 2002, 124, 2233. doi: 10.1021/ja012126h
10. [10]
  Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1997, 119, 8738. doi: 10.1021/ja971570a
11. [11]
  (a) Tobisu, M.; Chatani, N. Acc. Chem. Res. 2015, 48, 1717; (b) Guan, B.-T.; Xiang, S.-K.; Wu, T.; Sun, Z.-P.; Wang, B.-Q.; Zhao, K.-Q.; Shi, Z.-J. Chem. Commun. 2008, 1437; (c) Leiendecker, M.; Hsiao, C.-C.; Guo, L.; Alandini, N.; Rueping, M. Angew. Chem., Int. Ed. 2014, 53, 12912; (d) Tobisu, M.; Takahira, T.; Chatani, N. Org. Lett. 2015, 17, 4352.
12. [12]
  (a) Matsubara, H.; Ryu, I.; Schiesser, C. H. J. Org. Chem. 2005, 70, 3610; (b) Uenoyama, Y.; Fukuyama, T.; Nobuta, O.; Matsubara, H.; Ryu, I. Angew. Chem., Int. Ed. 2005, 44, 1075; (c) Fukuyama, T.; Nakashima, N.; Okada, T.; Ryu, I. J. Am. Chem. Soc. 2013, 135, 1006.
1. [1]
  Lei Shi . Nucleophilicity and Electrophilicity of Radicals. University Chemistry, 2024, 39(11): 131-135. doi: 10.3866/PKU.DXHX202402018
2. [2]
  Jiajia Li , Xiangyu Zhang , Zhihan Yuan , Zhengyang Qian , Jian Zhu . 3D Printing Based on Photo-Induced Reversible Addition-Fragmentation Chain Transfer Polymerization. University Chemistry, 2024, 39(5): 11-19. doi: 10.3866/PKU.DXHX202309073
3. [3]
  Zijian Zhao , Yanxin Shi , Shicheng Li , Wenhong Ruan , Fang Zhu , Jijun Jiang . A New Exploration of the Preparation of Polyacrylic Acid by Free Radical Polymerization Based on the Concept of Green Chemistry. University Chemistry, 2024, 39(5): 315-324. doi: 10.3866/PKU.DXHX202311094
4. [4]
  Danqing Wu , Jiajun Liu , Tianyu Li , Dazhen Xu , Zhiwei Miao . Research Progress on the Simultaneous Construction of C—O and C—X Bonds via 1,2-Difunctionalization of Olefins through Radical Pathways. University Chemistry, 2024, 39(11): 146-157. doi: 10.12461/PKU.DXHX202403087
5. [5]
  Zhiquan Zhang , Baker Rhimi , Zheyang Liu , Min Zhou , Guowei Deng , Wei Wei , Liang Mao , Huaming Li , Zhifeng Jiang . Insights into the Development of Copper-based Photocatalysts for CO₂ Conversion. Acta Physico-Chimica Sinica, 2024, 40(12): 2406029-. doi: 10.3866/PKU.WHXB202406029
6. [6]
  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
7. [7]
  Xinghai Liu , Hongke Wu . Exploration and Practice of Ideological and Political Education in Heterocyclic Chemistry Based on "Fentanyl" Event. University Chemistry, 2024, 39(8): 359-364. doi: 10.3866/PKU.DXHX202312100
8. [8]
  Siyu HOU , Weiyao LI , Jiadong LIU , Fei WANG , Wensi LIU , Jing YANG , Ying ZHANG . Preparation and catalytic performance of magnetic nano iron oxide by oxidation co-precipitation method. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1577-1582. doi: 10.11862/CJIC.20230469
9. [9]
  Junke LIU , Kungui ZHENG , Wenjing SUN , Gaoyang BAI , Guodong BAI , Zuwei YIN , Yao ZHOU , Juntao LI . Preparation of modified high-nickel layered cathode with LiAlO₂/cyclopolyacrylonitrile dual-functional coating. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1461-1473. doi: 10.11862/CJIC.20240189
10. [10]
  Endong YANG , Haoze TIAN , Ke ZHANG , Yongbing LOU . Efficient oxygen evolution reaction of CuCo₂O₄/NiFe-layered bimetallic hydroxide core-shell nanoflower sphere arrays. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 930-940. doi: 10.11862/CJIC.20230369
11. [11]
  Minna Ma , Yujin Ouyang , Yuan Wu , Mingwei Yuan , Lijuan Yang . Green Synthesis of Medical Chemiluminescence Reagents by Photocatalytic Oxidation. University Chemistry, 2024, 39(5): 134-143. doi: 10.3866/PKU.DXHX202310093
12. [12]
  Yunting Shang , Yue Dai , Jianxin Zhang , Nan Zhu , Yan Su . Something about RGO (Reduced Graphene Oxide). University Chemistry, 2024, 39(9): 273-278. doi: 10.3866/PKU.DXHX202306050
13. [13]
  Linbao Zhang , Weisi Guo , Shuwen Wang , Ran Song , Ming Li . Electrochemical Oxidation of Sulfides to Sulfoxides. University Chemistry, 2024, 39(11): 204-209. doi: 10.3866/PKU.DXHX202401009
14. [14]
  Chuanming GUO , Kaiyang ZHANG , Yun WU , Rui YAO , Qiang ZHAO , Jinping LI , Guang LIU . Performance of MnO₂-0.39IrO_x composite oxides for water oxidation reaction in acidic media. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1135-1142. doi: 10.11862/CJIC.20230459
15. [15]
  Zhihuan XU , Qing KANG , Yuzhen LONG , Qian YUAN , Cidong LIU , Xin LI , Genghuai TANG , Yuqing LIAO . Effect of graphene oxide concentration on the electrochemical properties of reduced graphene oxide/ZnS. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1329-1336. doi: 10.11862/CJIC.20230447
16. [16]
  Xiaofeng Zhu , Bingbing Xiao , Jiaxin Su , Shuai Wang , Qingran Zhang , Jun Wang . Transition Metal Oxides/Chalcogenides for Electrochemical Oxygen Reduction into Hydrogen Peroxides. Acta Physico-Chimica Sinica, 2024, 40(12): 2407005-. doi: 10.3866/PKU.WHXB202407005
17. [17]
  Kai CHEN , Fengshun WU , Shun XIAO , Jinbao ZHANG , Lihua ZHU . PtRu/nitrogen-doped carbon for electrocatalytic methanol oxidation and hydrogen evolution by water electrolysis. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1357-1367. doi: 10.11862/CJIC.20230350
18. [18]
  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
19. [19]
  Ping ZHANG , Chenchen ZHAO , Xiaoyun CUI , Bing XIE , Yihan LIU , Haiyu LIN , Jiale ZHANG , Yu'nan CHEN . Preparation and adsorption-photocatalytic performance of ZnAl@layered double oxides. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1965-1974. doi: 10.11862/CJIC.20240014
20. [20]
  Yongmei Liu , Lisen Sun , Zhen Huang , Tao Tu . Curriculum-Based Ideological and Political Design for the Experiment of Methanol Oxidation to Formaldehyde Catalyzed by Electrolytic Silver. University Chemistry, 2024, 39(2): 67-71. doi: 10.3866/PKU.DXHX202308020

Get Citation

PDF

XML

Metrics

PDF Downloads(13)
Abstract views(1366)
HTML views(354)

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