Citation: Xu Jian, Zhang Shifan, Luo Ying, Zhang Li, Zhang Fan, Huang Tingjing, Song Qiuling. Radical Promoted Annulation of Alkynones for the Construction of 2, 3-Disubstituted Thiochromones[J]. Acta Chimica Sinica, ;2019, 77(9): 932-938. doi: 10.6023/A19050169 shu

Radical Promoted Annulation of Alkynones for the Construction of 2, 3-Disubstituted Thiochromones

Xu Jian ^a,b ,
Zhang Shifan ^c ,
Luo Ying ^c ,
Zhang Li ^c ,
Zhang Fan ^c ,
Huang Tingjing ^c ,
Song Qiuling ^a,b,,

a.
College of Materials Science & Engineering, Huaqiao University, Xiamen 361021
b.
Institute of Next Generation Matter Transformation, Huaqiao University, Xiamen 361021
c.
College of Chemical Engineering, Huaqiao University, Xiamen 361021

Corresponding author: Song Qiuling, qsong@hqu.edu.cn
Received Date: 11 May 2019
Available Online: 6 September 2019
Fund Project: the National Natural Science Foundation of China 21602065Project supported by the National Natural Science Foundation of China (No. 21602065)

Figures(3)

Thiochromones are prevalent structures in various biological active molecules, natural products and potent drug candidates. However, only few methods for the synthesis of thiochromones were reported, and the traditional methods suffer from harsh conditions such as high temperature, strong acid, etc. Recently, synthesis of thiochromones from alkynones had been independently developed by the group of Larock, Müller and Fu. Compared to traditional substances, alkynones are easy to be prepared and handled. More recently, Wu and co-authors improved this synthetic approach via a palladium-catalyzed carbonylative four-component reaction. Despite these great advances, syntheses of diversely functionalized thiochromones, especially 2-functionalized thiochromones which were not easily prepared via the above approaches, are still in demand and highly desirable. As part of our on-going interest in the synthesis of heterocyclic compounds via radical cascade reactions, herein, we developed a radical-involved annulation of methylthiolatedalkynones with diverse radical precursors to access 2-substituted thiochromones. Various substituents such as F, Br and OMe on aromatic ring were all compatible with the reaction, affording the desired 2-substituted thiochromones in moderate to good yields. The most advantage of this protocol is the compatibility of diverse radical precursors including H-phosphorus oxides, aryl aldehydes, arylthiols, BrCF₂COOEt, acetone and acetonitrile. Moreover, a series of control experiments were performed to interpret the reaction pathway as a radical process instead of electrophilic cyclization process. Mechanism studies showed that radical involved C(sp²)-S bond formation and C(sp³)-S cleavage are the key steps. A general procedure for the radical annulation of alkynones with acetone and acetonitrile is as followed. To the mixture of alkynones 1 (0.2 mmol), in a schlenk flask was added a solution of tert-butyl peroxybenzoate (TBPB) (0.4 mmol) in acetone or acetonitrile (2 mL) under nitrogen atmosphere. The reaction was stirred at 130 or 120℃ for 12 h. Upon completion, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography using a petroleum ether/ethyl acetate (V:V, 8:1~5:1) to afford the corresponding products 6.
- radical,
- thiochromen,
- cyclization reaction,
- radical cascade reaction
1. [1]
  (a) Nakazumi, H.; Ueyama, T.; Kitao, T. J. Heterocycl. Chem. 1984, 21, 193. (b) Couquelet, J.; Tronche, P.; Niviere, P.; Andraud, G. Trav. Soc. Pharm. Montpellier 1963, 23, 214. (c) Nakazumi, H.; Ueyama, T.; Kitao, T. J. Heterocycl. Chem. 1984, 21, 193.
2. [2]
  (a) Holshouser, M. H.; Loeffler, L. J.; Hall, I. H. J. Med. Chem. 1981, 24, 853. (b) Razdan, R. K.; Bruni, R. J.; Mehta, A. C.; Weinhardt, K. K.; Papanastassiou, Z. B. J. Med. Chem. 1978, 21, 643.
3. [3]
  Dhanak, D.; Keenan, R. M.; Burton, G.; Kaura, A.; Darcy, M. G. D.; Shah, H.; Ridgers, L. H.; Breen, A.; Lavery, P.; Tew, D. G.; West, A. Bioorg. Med. Chem. Lett. 1998, 8, 3677. doi: 10.1016/S0960-894X(98)00666-0
4. [4]
  (a) Sangeetha, S.; Sekar, G. Org. Lett. 2018, 21, 75. (b) Zhang, F.; Wu, X. F. J. Org. Chem. 2018, 83, 13612. (c) Kim, H. Y.; Song, E.; Oh, K. Org. Lett. 2017, 19, 312. (d) Zhu, F.-X.; Wu, X.-F. J. Org. Chem. 2018, 83, 13612.
5. [5]
  (a) Schneller, S. W. Adv. Heterocycl. Chem. 1975, 18, 59. (b) Nakazumi, H.; Wanatabe, S.; Kitaguchi, T.; Kitao, T. Bull. Chem. Soc. Jpn. 1990, 63, 847. (c) Razdan, R. K.; Bruni, R. J.; Mehta, A. C.; Weinhardt, K. K.; Papanastassiou, Z. B. J. Med. Chem. 1978, 21, 643. (d) Buggle, K.; Delahunty, J. J.; Philbin, E. M.; Ryan, N. D. J. Chem. Soc. C 1971, 3168.
6. [6]
  Zhou, C.; Dubrovsky, A. V.; Larock, R. C. J. Org. Chem. 2006, 71, 1626. doi: 10.1021/jo0523722
7. [7]
  Willy, B.; Frank, W.; Müller, T. J. J. Org. Biomol. Chem. 2010, 8, 90. doi: 10.1039/B917627F
8. [8]
  Yang, X.-B.; Li, S.-F.; Liu, H.-X.; Jiang, Y.-Y.; Fu, H. RSC Adv. 2012, 2, 6549. doi: 10.1039/c2ra20897k
9. [9]
  Shen, C.-R.; Spannenberg, A.; Wu, X.-F. Angew. Chem., Int. Ed. 2016, 55, 5067. doi: 10.1002/anie.201600953
10. [10]
  (a) Pan, X.-Q.; Zou, J.-P.; Zhang, G.-L.; Zhang, W. Chem. Commun. 2010, 46, 1721. (b) Yan, Z.-F.; Xie, J.; Zhu, C.-J. Adv. Synth. Catal. 2017, 359, 4153. (c) Pan, C.-D.; Huang, B.-F.; Hu, W.-M.; Feng, X.-M.; Yu, J.-T. J. Org. Chem. 2016, 81, 2087. (d) Zhang, Y.; Ye, S.-Y.; Ji, M.-M.; Li, L.-S.; Guo, D.-M.; Zhu, G.-G. J. Org. Chem. 2017, 82, 6811. (e) Zhang, Y.; Guo, D.-M.; Ye, S.-Y.; Liu, Z.-C.; Zhu, G.-G. Org. Lett. 2017, 19, 1302. (f) Zhou, N.-N.; Yang, Z.-F.; Zhang, H.-L.; Wu, Z.-K.; Zhu, C.-J. J. Org. Chem. 2016, 81, 12181. (g) Zhang, Y.; Zhang, J.-H.; Hu, B.-Y.; Ji, M.-M.; Ye, S.-Y.; Zhu, G.-G. Org. Lett. 2018, 20, 2988.
11. [11]
  (a) Hari, D. P.; Hering, T.; Kcning, B. Org. Lett. 2012, 14, 5334. (b) Staples, M. K.; Grange, R. L.; Angus, J. A.; Ziogas, J.; Tan, N. P. H.; Taylor, K. T.; Schiesser, C. H. Org. Biomol. Chem. 2011, 9, 473. (c) Leardini, R.; Pedulli, G. F.; Tundo, A.; Huffman Jr, L. G. Synthesis 2000, 970. (d) Zang, H.; Sun, J. G.; Dong, X.; Li, P.; Zhang, B. Adv. Synth. Catal. 2016, 358, 1746. (e) Yang, W.-C.; Wei, K.; Sun, X.; Zhu, J.; Wu, L. Org. Lett. 2018, 20, 3144. (f) Xu, J.; Yu, X.-X.; Yan, J.-X.; Song, Q. Org. Lett. 2017, 19, 6292. (g) Gao, Y.-Z.; Zhang, P.-B.; Li, G.; Zhao, Y.-F. J. Org. Chem. 2018, 83, 13726. (h) Yan, J.-X.; Xu, J.; Zhou, Y.; Chen, J.; Song, Q. Org. Chem. Front 2018, 5, 1483. (i) Liu, W.; Hu, Y.-Q.; Hong, X.-Y.; Li, G.-X.; Huang, X.-B.; Gao, W.-X.; Liu, M.-C.; Xia, Y.; Zhou, Y.-B.; Wu, H.-Y. Chem. Commun. 2018, 54, 14148.
12. [12]
  Xu, J.; Zhang, F.; Zhang, S.-F.; Zhang, L.; Yu, X.-X.; Yan, J.-X. Song, Q. Org. Lett. 2019, 21, 1112.
13. [13]
  Liu, Q.-Y.; Zhao, X.-H.; Li, J.-L.; Cao, S. Acta Chim. Sinica 2018, 76, 945. doi: 10.3866/PKU.WHXB201801292
1. [1]
  Lei Shi . Nucleophilicity and Electrophilicity of Radicals. University Chemistry, 2024, 39(11): 131-135. doi: 10.3866/PKU.DXHX202402018
2. [2]
  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
3. [3]
  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
4. [4]
  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
5. [5]
  Jinyao Du , Xingchao Zang , Ningning Xu , Yongjun Liu , Weisi Guo . Electrochemical Thiocyanation of 4-Bromoethylbenzene. University Chemistry, 2024, 39(6): 312-317. doi: 10.3866/PKU.DXHX202310039
6. [6]
  Chengqian Mao , Yanghan Chen , Haotong Bai , Junru Huang , Junpeng Zhuang . Photodimerization of Styrylpyridinium Salt and Its Application in Silk Screen Printing. University Chemistry, 2024, 39(5): 354-362. doi: 10.3866/PKU.DXHX202312014
7. [7]
  Yinuo Wang , Siran Wang , Yilong Zhao , Dazhen Xu . Selective Synthesis of Diarylmethyl Anilines and Triarylmethanes via Multicomponent Reactions: Introduce a Comprehensive Experiment of Organic Chemistry. University Chemistry, 2024, 39(8): 324-330. doi: 10.3866/PKU.DXHX202401063
8. [8]
  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
9. [9]
  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
10. [10]
  Renxiao Liang , Zhe Zhong , Zhangling Jin , Lijuan Shi , Yixia Jia . A Palladium/Chiral Phosphoric Acid Relay Catalysis for the One-Pot Three-Step Synthesis of Chiral Tetrahydroquinoline. University Chemistry, 2024, 39(5): 209-217. doi: 10.3866/PKU.DXHX202311024
11. [11]
  Daojuan Cheng , Fang Fang . Exploration and Implementation of Science-Education Integration in Organic Chemistry Teaching for Pharmacy Majors: A Case Study on Nucleophilic Substitution Reactions of Alkyl Halides. University Chemistry, 2024, 39(11): 72-78. doi: 10.12461/PKU.DXHX202403105
12. [12]
  Wentao Lin , Wenfeng Wang , Yaofeng Yuan , Chunfa Xu . Concerted Nucleophilic Aromatic Substitution Reactions. University Chemistry, 2024, 39(6): 226-230. doi: 10.3866/PKU.DXHX202310095
13. [13]
  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
14. [14]
  Yuting Zhang , Zhiqian Wang . Methods and Case Studies for In-Depth Learning of the Aldol Reaction Based on Its Reversible Nature. University Chemistry, 2024, 39(7): 377-380. doi: 10.3866/PKU.DXHX202311037
15. [15]
  Ruitong Zhang , Zhiqiang Zeng , Xiaoguang Zhang . Improvement of Ethyl Acetate Saponification Reaction and Iodine Clock Reaction Experiments. University Chemistry, 2024, 39(8): 197-203. doi: 10.3866/PKU.DXHX202312004
16. [16]
  Yuan Chun , Lijun Yang , Jinyue Yang , Wei Gao . Ideological and Political Design of BZ Oscillatory Reaction Experiment. University Chemistry, 2024, 39(2): 72-76. doi: 10.3866/PKU.DXHX202308072
17. [17]
  Shiyan Cheng , Yonghong Ruan , Lei Gong , Yumei Lin . Research Advances in Friedel-Crafts Alkylation Reaction. University Chemistry, 2024, 39(10): 408-415. doi: 10.12461/PKU.DXHX202403024
18. [18]
  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
19. [19]
  Honglian Liang , Xiaozhe Kuang , Fuping Wang , Yu Chen . Exploration and Practice of Integrating Ideological and Political Education into Physical Chemistry: a Case on Surface Tension and Gibbs Free Energy. University Chemistry, 2024, 39(10): 433-440. doi: 10.12461/PKU.DXHX202405073
20. [20]
  Feiya Cao , Qixin Wang , Pu Li , Zhirong Xing , Ziyu Song , Heng Zhang , Zhibin Zhou , Wenfang Feng . Magnesium-Ion Conducting Electrolyte Based on Grignard Reaction: Synthesis and Properties. University Chemistry, 2024, 39(3): 359-368. doi: 10.3866/PKU.DXHX202308094

Get Citation

PDF

XML

Metrics

PDF Downloads(13)
Abstract views(1254)
HTML views(274)

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