Citation: Dai Jianling, Lei Wenlong, Liu Qiang. Visible-Light-Driven Difluoroalkylation of Aromatics Catalyzed by Copper[J]. Acta Chimica Sinica, ;2019, 77(9): 911-915. doi: 10.6023/A19050181 shu

Visible-Light-Driven Difluoroalkylation of Aromatics Catalyzed by Copper

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000

Corresponding author: Liu Qiang, liuqiang@lzu.edu.cn
Received Date: 15 May 2019
Available Online: 14 September 2019
Fund Project: the National Natural Science Foundation of China 21572090the National Natural Science Foundation of China 21871123Project supported by the National Natural Science Foundation of China (Nos. 21572090 and 21871123) and the Fundamental Research Funds for the Central Universities (lzujbky-2017-k05)the Fundamental Research Funds for the Central Universities lzujbky-2017-k05

Figures(2)

The introduction of difluoromethyl groups into organic molecules not only can dramatically alter physical properties of nonfluorinated counterparts, but also provide valuable CF₂-containing building blocks for the synthesis of other difluoromethylenated compounds. Therefore, there is a growing demand to develop efficient and practical methods for the introduction of the difluoromethyl motif. Although significant advances have been made in the preparation of difluoromethylated arenes, these reactions usually required pre-functionalized substrates, precious metal catalysts, elevated temperature, and so on. In the past decade, visible light-driven photoredox catalysis has been proved to be powerful in synthetic radical chemistry. Particularly, direct difluoroalkylations of arenes have been achieved using precious-metal photocatalysts such as ruthenium or iridium polypyridyl complexes. Herein, we are committed to developing a cheap copper-based phororedox system for direct difluoroalkylation of arenes. The key to this approach is the in-situ formation of cuprous photocatalyst from cuprous iodide, an imine ligand (2, 9-dichloro-1, 10-phenanthroline) and a triaryl phosphine ligand (4, 5-bis(diphenylphos-phino)-9, 9-dimethyl xanthene). With catalytic amount of reagents mentioned above, the direct difluoroalkylation between arenes and difluoroalkylation reagents (BrCF₂CO₂Et or BrCF₂CONR¹R²) took place smoothly under 6 W blue LED irradiation at room temperature. A variety of electron-rich arenes, including electron-donating aromatics, indoles, furans, thiophenes, and pyrimidines, could be carbonyldifluoromethylated in moderate to excellent yields. In addition, high yields were obtained for the intramolecular and intermolecular aminocarbonyldifluoromethylation by the catalytic system. Preliminary mechanistic studies reveal that[Cu(dcp)(xantphos)]Ⅰ (dcp=2, 9-dichloro-1, 10-phenanthroline, xantphos=4, 5-bis(diphenyl phosphino)-9, 9-dimethyl xanthene), in situ-formed from CuI, dcp, and xantphos should be the real photocatalyst to catalyze the visible light-driven difluoroalkylation. Difluormethyl radicals, produced by single electron transfer from the excited photocatalyst to difluoroalkylation reagents, should be involved in the difluoroalkylation. In summary, visible-light driven difluoroalkylation of arenes with difluoroalkylation reagents via Cu-catalysis has been developed. The use of the bidentate phosphine ligand and the imine ligand is essential for high efficiency as they could bind to cuprous iodide to generate the photocatalyst in situ. The typical procedure is as follows:a mixture of arenes (0.6 mmol), CuI (0.02 mmol), dcp (0.02 mmol), xantphos (0.02 mmol), K₃PO₄(0.4 mmol) and CH₂Cl₂ (2 mL) were loaded in a flame-dried reaction vial which was subjected to evacuation with argon for 30 min. Subsequently, BrCF₂CO₂Et (0.2 mmol) was added to the mixture via syringe, and the mixture continued degassing for 5 min. After degassing procedure, the vial was sealed with wax, and irradiated by blue light for 24 h. The reaction was monitored by TLC. Further purification of the evaporated mixture by flash column chromatography on silica gel (eluent:petroleum ether/ethyl acetate) gave the desired product.
- alkyl radical,
- visible-light photocatalysis,
- difluoroalkylation,
- arenes,
- copper
1. [1]
  (a) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881. (b) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
2. [2]
  (a) Jeschke, P. ChemBioChem 2004, 5, 570. (b) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. (c) Wang, J.; Sanchez-Rosello, M.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev. 2014, 114, 2432.
3. [3]
  (a) Bégué, J. P.; Bonnet-Delpon, D. J. Fluorine Chem. 2006, 127, 992. (b) Isanbor, C. J. Fluorine Chem. 2006, 127, 303. (c) Kirk, K. L. J. Fluorine Chem. 2006, 127, 1013.
4. [4]
  Wong, D. T.; Bymaster, F. P.; Engleman, E. A. Life Sci. 1995, 57, 411. doi: 10.1016/0024-3205(95)00209-O
5. [5]
  Roth, B. D. In Progress in Medicinal Chemistry, Vol. 40, Eds.: King, F. D.; Oxford, A. W., Elsevier, Amsterdam, 2002, pp. 1~22.
6. [6]
  Drlica, K.; Malik, M. Curr. Top. Med. Chem. 2003, 3, 249. doi: 10.2174/1568026033452537
7. [7]
  (a) Purser, S.; Moore, P.-R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. (b) Nenajdenko, V. G.; Shastin, A. V. Chem. Rev. 2015, 115, 973. (c) Ni, C.-F.; Hu, J.-B. Chem. Rev. 2015, 115, 765. (d) Liang, T.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214. (e) Zhou, B.-Y.; Cheng, J.-P. Org. Lett. 2016, 18, 6128. (f) Yu, W.; Qing, F.-L. Org. Lett. 2016, 18, 5130. (g) Guo, W.-H.; Zhang, X. ACS Catal. 2017, 7, 896. (h) Fu, X.-P.; Xiao, Y.-L.; Zhang, X. Chin. J. Chem. 2018, 36, 143. (i) He, X.; Gao, X.; Zhang, X. Chin. J. Chem. 2018, 36, 1059. (j) Fujiwara, Y. J.; Dixon, A.; Baran, P. S. J. Am. Chem. Soc. 2012, 134, 1494. (k) Xu, L.; Vicic, D. A. J. Am. Chem. Soc. 2016, 138, 2536. (l) Qi, Q.-Q.; Shen, Q.-L.; Lu, L. J. Am. Chem. Soc. 2012, 134, 6548. (m) Feng, Z.; Zhang, X. Org. Lett. 2016, 18, 44. (n) Ruan, Z.-X.; Zhang, S.-K.; Ackermann, L. Angew. Chem., Int. Ed. 2017, 56, 2045.
8. [8]
9. [9]
  (a) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529. (b) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822.
10. [10]
11. [11]
  Shi, S.-L.; Buchwald, S.-L. Angew. Chem. Int. Ed. 2017, 129, 2077. doi: 10.1002/ange.201611595
12. [12]
  (a) Belhomme, M.-C.; Poisson, T.; Pannecoucke, X. J. Org. Chem. 2014, 79, 7205; (b) Wang, L.-P.; Liu, H.-Y.; Li, F.-F.; Zhao, J.-Q.; Zhang, H.-Y.; Zhang, Y.-C. Adv. Synth. Catal. 2019, 361, 2354.
13. [13]
  (a) Ruan, Z.-X.; Zhang, S.-K.; Zhu, C.-J.; Ruth, P.-N.; Stalke, D.; Ackermann, L. Angew. Chem., Int. Ed. 2017, 129, 2077; (b) Li, Z.-Y.; Li, L.; Li, Q.-L.; Jing, K.; Xu, H.; Wang, G.-W. Chem. Eur. J., 2017, 23, 3285. (c) Yuan, C.-C.; Chen, X.-L.; Zhang, J.-Y.; Zhao, Y.-S. Org. Chem. Front. 2017, 4, 1867.
14. [14]
  (a) Chen, Y.-Y.; Lu, L.-Q.; Yu, D.-G.; Zhu, C.-J.; Xiao, W.-J. Sci China Chem. 2019, 62, 24. (b) Liu, Q.; Wu, L.-Z. Nat. Sci. Rev. 2017, 4, 359. (d) Skubi, K. L.; Yoon, T. P. Nature 2014, 515, 45.
15. [15]
  (a) Lin, Q.; Chu, L.; Qing, F. Chin. J. Chem. 2013, 31, 885. (b) Yu, X.; Xu, X.-H.; Qing, F. Org. Lett. 2016, 18, 5130. (c) Su, Y.-M.; Hou, Y.; Yin, F.; Xu, Y.-M.; Li, Y.; Zheng, X.; Wang, X. Org. Lett. 2014, 16, 2958. (d) Jung, J.; Kim, E.; You, Y.; Cho, E. J. Adv. Synth. Catal. 2014, 356, 2741. (e) McAtee, R.-C.; Beatty, J.-W.; McAtee, C.-C.; Stephenson, C. R. J. Org. Lett. 2018, 20, 3491. (f) Wang, L.; Wei, X.-J.; Lei, W.-L.; Chen, H.; Wu, L.-Z.; Liu, Q. Chem. Commun. 2014, 50, 15916. (g) Wang, L.; Wei, X.-J.; Jia, W.-L.; Zhong, J.-J.; Wu, L.-Z.; Liu, Q. Org. Lett. 2014, 16, 5842.
16. [16]
  (a) Paria, S.; Reiser, O. ChemCatChem 2014, 6, 2477. (b) Reiser, O. Acc. Chem. Res. 2016, 49, 1990. (c) Hernandez-Perez, A. C.; Collins, S. K. Acc. Chem. Res. 2016, 49, 1557. (d) Cuttell, D. G.; Kuang, S.-M.; Fanwick, P. E.; McMillin, D. R.; Walton, R. J. Am. Chem. Soc. 2002, 124, 6. (e) McMillin, D. R.; McNett, K. M. Chem. Rev. 1998, 98, 1201. (f) Cuttell, D. G.; Kuang, S.-M.; Fanwick, P. E.; McMillin, D. R.; Walton, R. A. J. Am. Chem. Soc. 2002, 124, 6.
17. [17]
  (a) Huang, J.; Mara, M. W.; Stickrath, A. B.; Kokhan, O.; Harpham, M. R.; Haldrup, K.; Shelby, M. L.; Zhang, X.; Ruppert, R.; Sauvage, J.-P.; Chen, L. X. Dalton Trans. 2014, 43, 17615. (b) Pirtsch, M.; Paria, S.; Matsuno, T.; Isobe, H. T.; Reiser, O. Chem. Eur. J. 2012, 18, 7336. (c) Paria, S.; Pirtsch, M.; Kais, V.; Reiser, O. Synthesis 2013, 45, 2689. (d) Tang, X.-J.; Dolbier, W. R., Jr. Angew. Chem., Int. Ed. 2015, 54, 4246. (e) Bagal, D. B.; Kachkovskyi, G.; Knorn, M.; Rawner, T.; Bhanage, B. M.; Reiser, O. Angew. Chem., Int. Ed. 2015, 54, 6999. (f) Fumagalli, G.; Rabet, P. T. G.; Boyd, S.; Greaney, M. F. Angew. Chem., Int. Ed. 2015, 54, 11481. (g) Rabet, P. T. G.; Fumagalli, G.; Boyd, S.; Greaney, M. F. Org. Lett. 2016, 18, 1646. (h) Hossain, A.; Engl, S.; Lutsker, E.; Reiser, O. ACS Catal. 2019, 9, 1103.
18. [18]
  (a) Hernandez-Perez, A. C.; Vlassova, A.; Collins, S. K. Org. Lett. 2012, 14, 2988. (b) Knorn, M.; Rawner, T.; Czerwieniec, R.; Reiser, O. ACS Catal. 2015, 5, 5186. (c) Murat, A.-Z.; Hu, X.-L. Organometallics 2018, 37, 3928. (d) Brunner, F.; Graber, S.; Baumgartner, Y.; Haussinger, D.; Prescimone, A.; Constable, E. C.; Housecroft, C. E. Dalton Trans. 2017, 46, 6379. (e) Nitelet, N.; Thevenet, D.; Schiavi, B.; Hardouin, C.; Fournier, J.; Tamion, R.; Pannecoucke, X.; Jubault, P.; Poisson, T. Chem. Eur. J. 2019, 25, 3262. (f) Wang, B.; Shelar, D. P.; Han, X.-Z.; Li, T.-T.; Guan, X.-G. Chem. Eur. J. 2015, 21, 1184. (g) Michelet, B.; Deldaele, C.; Kajouj, S.; Moucheron, C.; Evano, G. Org. Lett. 2017, 19, 3576. (h) Lu, W.; Liu, K.; Chen, Y.; Fu, W.-F.; Che, C.-M. Chem. Eur. J. 2015, 21, 1184.
19. [19]
  (a) Hernandez-Perez, A. C.; Collins, S. K. Angew. Chem. Int. Ed. 2013, 52, 12696. (b) Hernandez-Perez, A. C.; Collins, S. K. Angew. Chem. Int. Ed. 2013, 125, 12928. (c) Hernandez-Perez, A. C.; Vlassova, A.; Collins, S. K. Org. Lett. 2012, 14, 2988.
20. [20]
  (a) Ahn, J. M.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2017, 139, 18101. (b) Zhao, W.; Wurz, R. P.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2017, 139, 12153.
21. [21]
  Wang, W.; Guo, M.-Z.; Qi, R.-P.; Shang, Q.-Y.; Liu, Q.; Wang, S.; Zhao, L.; Wang, R.; Xu, Z.-Q. Angew. Chem. Int. Ed. 2018, 57, 15841. doi: 10.1002/anie.201809400
22. [22]
  Zhang, B.; Daniliuc, C. G.; Studer, A. Angew. Chem., Int. Ed. 2013, 52, 10792 doi: 10.1002/anie.201306082
1. [1]
  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
2. [2]
  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
3. [3]
  Min LIU , Huapeng RUAN , Zhongtao FENG , Xue DONG , Haiyan CUI , Xinping WANG . Neutral boron-containing radical dimers. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 123-130. doi: 10.11862/CJIC.20240362
4. [4]
  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
5. [5]
  Bo YANG , Gongxuan LÜ , Jiantai MA . Nickel phosphide modified phosphorus doped gallium oxide for visible light photocatalytic water splitting to hydrogen. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 736-750. doi: 10.11862/CJIC.20230346
6. [6]
  Xinzhe HUANG , Lihui XU , Yue YANG , Liming WANG , Zhangyong LIU , Zhongjian WANG . Preparation and visible light responsive photocatalytic properties of BiSbO₄/BiOBr. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 284-292. doi: 10.11862/CJIC.20240212
7. [7]
  .
  CCS Chemistry | 超分子活化底物为自由基促进高效选择性光催化氧化
  . CCS Chemistry, 2025, 7(10.31635/ccschem.025.202405229): -.
8. [8]
  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
9. [9]
  Qin Li , Huihui Zhang , Huajun Gu , Yuanyuan Cui , Ruihua Gao , Wei-Lin Dai . In situ Growth of Cd_0.5Zn_0.5S Nanorods on Ti₃C₂ MXene Nanosheet for Efficient Visible-Light-Driven Photocatalytic Hydrogen Evolution. Acta Physico-Chimica Sinica, 2025, 41(4): 100031-. doi: 10.3866/PKU.WHXB202402016
10. [10]
  Baitong Wei , Jinxin Guo , Xigong Liu , Rongxiu Zhu , Lei Liu . Theoretical Study on the Structure, Stability of Hydrocarbon Free Radicals and Selectivity of Alkane Chlorination Reaction. University Chemistry, 2025, 40(3): 402-407. doi: 10.12461/PKU.DXHX202406003
11. [11]
  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
12. [12]
  Bing LIU , Huang ZHANG , Hongliang HAN , Changwen HU , Yinglei ZHANG . Visible light degradation of methylene blue from water by triangle Au@TiO₂ mesoporous catalyst. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 941-952. doi: 10.11862/CJIC.20230398
13. [13]
  Jie Li , Huida Qian , Deyang Pan , Wenjing Wang , Daliang Zhu , Zhongxue Fang . Efficient Synthesis of Anethaldehyde Induced by Visible Light. University Chemistry, 2024, 39(4): 343-350. doi: 10.3866/PKU.DXHX202310076
14. [14]
  Yunhao Zhang , Yinuo Wang , Siran Wang , Dazhen Xu . Progress in Selective Construction of Functional Aromatics from Nitrogenous Cycloalkanes. University Chemistry, 2024, 39(11): 136-145. doi: 10.3866/PKU.DXHX202401083
15. [15]
  Shihui Shi , Haoyu Li , Shaojie Han , Yifan Yao , Siqi Liu . Regioselectively Synthesis of Halogenated Arenes via Self-Assembly and Synergistic Catalysis Strategy. University Chemistry, 2024, 39(5): 336-344. doi: 10.3866/PKU.DXHX202312002
16. [16]
  Lei Shi . Nucleophilicity and Electrophilicity of Radicals. University Chemistry, 2024, 39(11): 131-135. doi: 10.3866/PKU.DXHX202402018
17. [17]
  Jiapei Zou , Junyang Zhang , Xuming Wu , Cong Wei , Simin Fang , Yuxi Wang . A Comprehensive Experiment Based on Electrocatalytic Nitrate Reduction into Ammonia: Synthesis, Characterization, Performance Exploration, and Applicable Design of Copper-based Catalysts. University Chemistry, 2024, 39(6): 373-382. doi: 10.3866/PKU.DXHX202312081
18. [18]
  Geyang Song , Dong Xue , Gang Li . Recent Advances in Transition Metal-Catalyzed Synthesis of Anilines from Aryl Halides. University Chemistry, 2024, 39(2): 321-329. doi: 10.3866/PKU.DXHX202308030
19. [19]
  Zhen Yao , Bing Lin , Youping Tian , Tao Li , Wenhui Zhang , Xiongwei Liu , Wude Yang . Visible-Light-Mediated One-Pot Synthesis of Secondary Amines and Mechanistic Exploration. University Chemistry, 2024, 39(5): 201-208. doi: 10.3866/PKU.DXHX202311033
20. [20]
  Jiarui Wu , Gengxin Wu , Yan Wang , Yingwei Yang . Crystal Engineering Based on Leaning Towerarenes. University Chemistry, 2024, 39(3): 58-62. doi: 10.3866/PKU.DXHX202304014

Get Citation

PDF

XML

Metrics

PDF Downloads(14)
Abstract views(1306)
HTML views(275)

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