Citation: An Lun, Tong Feifei, Zhang Xingang. Iron-Catalyzed Cross-Coupling of Diarylzinc or Aryl Grignard Reagents with Difluoroalkyl Bromides[J]. Acta Chimica Sinica, ;2018, 76(12): 977-982. doi: 10.6023/A18080314 shu

Iron-Catalyzed Cross-Coupling of Diarylzinc or Aryl Grignard Reagents with Difluoroalkyl Bromides

Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Corresponding author: Zhang Xingang, xgzhang@sioc.ac.cn
Received Date: 18 September 2018
Available Online: 11 December 2018
Fund Project: the Strategic Priority Research Program of the Chinese Academy of Sciences XDB20000000the National Natural Science Foundation of China 21332010the National Natural Science Foundation of China 21425208Project supported by the National Basic Research Program of China (973 Program) (No. 2015CB931900), the National Natural Science Foundation of China (Nos. 21425208, 21672238, 21332010 and 21421002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB20000000)the National Natural Science Foundation of China 21421002the National Natural Science Foundation of China 21672238the National Basic Research Program of China (973 Program) 2015CB931900

Figures(5)

The demanding of discovering new pharmaceuticals, agrochemicals and advanced functional materials have triggered extensive efforts on efficient synthesis of fluorinated compounds. Over the past decade, the transition-metal-catalyzed fluoroalkylation has emerged as an efficient and straightforward strategy for the synthesis of organofluorine compounds. Despite the importance of the reported synthetic methods, the development of environmentally benign and cost-efficient fluoroalkylation reactions with base metals as catalysis and widely available fluoroalkyl halides as fluoroalkyl sources continues to attract great interest. Here, we reported the first example of iron-catalyzed cross-coupling of diarylzinc reagents with gem-difluoropropargyl bromides. The reaction proceeds under mild reaction conditions and provides a facile access to gem-difluoropropargyl arenes. Additionally, this iron-catalytic system can also be applied to the cross-coupling of aryl Grignard reagents with difluoroalkyl bromides. Applications of the method led to modified bioactive molecules efficiently, offering potential opportunities in medicinal chemistry. Preliminary mechanistic studies reveal that a single electron transfer pathway is involved in the reaction. A representative procedure for iron-catalyzed cross-coupling of diarylzincs with gem-difluoropropargyl bromide is as following: Fe(acac)₃ (10 mol%) was added to a 25 mL of Schlenck tube, the tube was then evacuated and backfilled with Ar (3 times). gem-Difluoropropargyl bromide 2 (0.3 mmol, 1.0 equiv.), TMEDA (0.45 mmol, 1.5 equiv.) and THF (1 mL) were then added, the reaction mixture was stirred at room temperature for 10 min and cooled to -20 ℃. A solution of diarylzinc reagent (0.45 mmol in 1.5 mL of THF, 1.5 equiv.) was added dropwise. After stirring for 4 h at -20 ℃, the reaction mixture was quenched with saturated NH₄Cl solution. The yield was determined by ¹⁹F NMR before working up. If necessary, the reaction mixture was diluted with EtOAc and filtered with a pad of cellite. The filtrate was concentrated, and the residue was purified with silica gel chromatography to give product 3.
- iron,
- diarylzinc reagents,
- gem-difluoropropargyl bromide,
- cross-coupling
1. [1]
  For selected reviews, see: (a) Hiyama, T. Organofluorine Compounds, Chemistry and Applications, Springer-Verlag, Berlin Heidelberg, 2000. (b) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881. (c) O' Hagan, D. Chem. Soc. Rev. 2008, 37, 308. (d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
2. [2]
  (a) Blackburn, C. M.; England, D. A.; Kolkmann, F. J. Chem. Soc. Chem. Commun. 1981, 930. (b) Blackburn, G. M.; Kent, D. E.; Kolkmann, F. J. Chem. Soc., Perkin Trans. 1 1984, 1119. (c) Kitazume, T.; Kamazaki, T. Experimental Methods in Organic Fluorine Chemistry, Gordon and Breach Science, Tokyo, 1998. (d) Yang, Y.; You, Z.; Qing, F.-L. Acta Chim. Sinica 2012, 70, 2323(in Chinese). (杨义, 游正伟, 卿凤翎, 化学学报, 2012, 70, 2323.)
3. [3]
  For selected reviews, see: (a) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529. (b) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822.
4. [4]
  For selected examples, see: (a) Xue, F.; Li, H.; Delker, S. L.; Fang, J.; Martasek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. J. Am. Chem. Soc. 2010, 132, 14229. (b) Anderson, M. O.; Zhang, J.; Liu, Y.; Yao, C.; Phuan, P.-W.; Verkman, A. S. J. Med. Chem. 2012, 55, 5942. (c) Matthew, A. N.; Zephyr, J.; Hill, C. J.; Jahangir, M.; Newton, A.; Petropoulos, C. J.; Huang, W.; Kurt-Yilmaz, N.; Schiffer, C. A.; Ali, A. J. Med. Chem. 2017, 60, 5699.
5. [5]
  (a) Markovsi, L. N.; Pahinnik, V. E.; Kirsanov, A. V. Synthesis 1973, 12, 787. (b) Middleton, W. J. J. Org. Chem. 1975, 40, 574.
6. [6]
  For selected reviews regarding fluorination and trifluoromethylation, see: (a) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470. (b) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475.
7. [7]
  For transition-metal-catalyzed difluoroalkylation, see: (a) Chen, B.; Vicic, D. A. Top. Organomet. Chem. 2014, 52, 113. (b) Ni, C.; Zhu, L.; Hu, J. Acta Chim. Sinica 2015, 73, 90(in Chinese). (倪传法, 朱林桂, 胡金波, 化学学报, 2015, 73, 90.) (c) Wang, W.; Yu, Q.; Zhang, Q.; Li, J.; Hui, F.; Yang, J.; LÜ, J. Chin. J. Org. Chem. 2018, 38, 1569(in Chinese). (王为强, 余秦伟, 张前, 李江伟, 惠丰, 杨建明, 吕剑, 有机化学, 2018, 38, 1569.)
8. [8]
  (a) McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25, 2921. (b) Kobayashi, Y.; Kumadaki, I. Tetrahedron Lett. 1969, 10, 4095. (c) Taguchi, T.; Kitagawa, O.; Morikawa, T.; Nishiwaki, T.; Uehara, H.; Endo, H.; Kobayashi, Y. Tetrahedron Lett. 1986, 27, 6103.
9. [9]
  (a) Chen, Q.-Y.; Yang, Z.-Y. J. Fluorine Chem. 1985, 28, 399. (b) Chen, Q.-Y.; Yang, Z.-Y. Acta Chim. Sinica 1985, 43, 1118(in Chinese). (陈庆云, 杨振宇, 化学学报, 1985, 43, 1118.) (c) Zhou, Q.-L.; Huang, Y.-Z. J. Fluorine Chem. 1989, 43, 385. (d) Huang, W.-Y. Youji Huaxue, 1992, 12, 12(in Chinese). (黄维垣, 有机化学, 1992, 12, 12) (e) Huang, X.-T.; Long, Z.-Y.; Chen, Q.-Y. J. Fluorine Chem. 2001, 111, 107.
10. [10]
  (a) Feng, Z.; Xiao, Y.-L.; Zhang, X. Acc. Chem. Res. 2018, 51, 2264. (b) Feng, Z.; Chen, F.; Zhang, X. Org. Lett. 2012, 14, 1938. (c) Min, Q.-Q.; Yin, Z.; Feng, Z.; Guo, W.-H.; Zhang, X. J. Am. Chem. Soc. 2014, 136, 1230. (d) Feng, Z.; Min, Q.-Q.; Xiao, Y.-L.; Zhang, B.; Zhang, X. Angew. Chem., Int. Ed. 2014, 53, 1669. (e) Xiao, Y.-L.; Guo, W.-H.; He, G.-Z.; Pan, Q.; Zhang, X. Angew. Chem., Int. Ed. 2014, 53, 9909. (f) Feng, Z.; Min, Q.-Q.; Fu, X.-P.; An, L.; Zhang, X. Nat. Chem. 2017, 9, 918. (g) An, L.; Xu, C.; Zhang, X. Nat. Commun. 2017, 8, 1460.
11. [11]
  For selected reviews, see: (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217. (b) Sherry, B. D.; FÜrstner, A. Acc. Chem. Res. 2008, 41, 1500. (c) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417. (d) Nakamura, E.; Hatakeyama, T.; Ito, S.; Ishizuka, K.; Ilies, L.; Nakamura, M. Org. React. 2014, 83, 1. (e) Bauer, I.; Kn lker, H.-J. Chem. Rev. 2015, 115, 3170. (f) Kuzmina, O. M.; Steib, A. K.; Moyeux, A.; Cahiez, G.; Knochel, P. Synthesis 2015, 47, 1696. (g) Bedford, R. B. Acc. Chem. Res. 2015, 48, 1485. (h) Mako, T. L.; Byers, J. A. Inorg. Chem. Front. 2016, 3, 766. (i) Shang, R.; Ilies, L.; Nakamura, E. Chem. Rev. 2017, 117, 9086.
12. [12]
  For an iron-catalyzed cross-coupling of a-halo-b, b-difluoroethylene-containing compounds, see: (a) Lin, X.; Zheng, F.; Qing, F.-L. Organometallics 2012, 31, 1578. For an iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone, see: (b) Miao, W.; Zhao, Y.; Ni, C.; Gao, B.; Zhang, W.; Hu, J. J. Am. Chem. Soc. 2018, 140, 880.
13. [13]
  An, L.; Xiao, Y.-L.; Zhang, X. Angew. Chem., Int. Ed. 2018, 57, 6921. doi: 10.1002/anie.v57.23
14. [14]
  Xu, B.; Mashuta, M. S.; Hammond, G. B. Angew. Chem., Int. Ed. 2006, 45, 7265. doi: 10.1002/(ISSN)1521-3773
15. [15]
  (a) Yu, Y.-B.; He, G.-Z.; Zhang, X. Angew. Chem., Int. Ed. 2014, 53, 10457. (b) Guo, W.-H.; Luo, Z.-J.; Zeng, W.; Zhang, X. ACS Catal. 2017, 7, 896. (c) Xiao, Y.-L.; Pan, Q.; Zhang, X. Acta Chim. Sinica 2015, 73, 383(in Chinese). (肖玉兰, 潘强, 张新刚, 化学学报, 2015, 73, 383.)
16. [16]
  (a) Furstner, A.; Martin, R.; Krause, H.; Seidel, G.; Goddard, R.; Lehmann, C. W. J. Am. Chem. Soc. 2008, 130, 8773. (b) Noda, D.; Sunada, Y.; Hatakeyama, T.; Nakamura, M.; Nagashima, H. J. Am. Chem. Soc. 2009, 131, 6078. (c) Bedford, R. B.; Brenner, P. B.; Carter, E.; Cogswell, P. M.; Haddow, M. F.; Harvey, J. N.; Murphy, D. M.; Nunn, J.; Woodall, C. H. Angew. Chem., Int. Ed. 2014, 53, 1804.
17. [17]
  (a) Hedstrçm, A.; Izakian, Z.; Vreto, I.; Wallentin, C.-J.; Norrby, P. Chem. Eur. J. 2015, 21, 5946; (b) Daifuku, S. L.; Kneebone, J. L.; Snyder, B. E. R.; Neidig, M. L. J. Am. Chem. Soc. 2015, 137, 11432; (c) Kneebone, J. L.; Brennessel, W. W.; Neidig, M. L. J. Am. Chem. Soc. 2017, 139, 6988.
18. [18]
  (a) Sharma, A. K.; Sameera, W. M. C.; Jin, M.; Adak, L.; Okuzono, C.; Iwamoto, T.; Kato, M.; Nakamura, M.; Morokuma, K. J. Am. Chem. Soc. 2017, 139, 16126. (b) Lee, W.; Zhou, J.; Gutierrez, O. J. Am. Chem. Soc. 2017, 139, 16126.
1. [1]
  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
2. [2]
  Xiuyun Wang , Jiashuo Cheng , Yiming Wang , Haoyu Wu , Yan Su , Yuzhuo Gao , Xiaoyu Liu , Mingyu Zhao , Chunyan Wang , Miao Cui , Wenfeng Jiang . Improvement of Sodium Ferric Ethylenediaminetetraacetate (NaFeEDTA) Iron Supplement Preparation Experiment. University Chemistry, 2024, 39(2): 340-346. doi: 10.3866/PKU.DXHX202308067
3. [3]
  Jianfeng Yan , Yating Xiao , Xin Zuo , Caixia Lin , Yaofeng Yuan . Comprehensive Chemistry Experimental Design of Ferrocenylphenyl Derivatives. University Chemistry, 2024, 39(4): 329-337. doi: 10.3866/PKU.DXHX202310005
4. [4]
  Baohua LÜ , Yuzhen LI . Anisotropic photoresponse of two-dimensional layered α-In₂Se₃(2H) ferroelectric materials. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1911-1918. doi: 10.11862/CJIC.20240105
5. [5]
  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
6. [6]
  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
7. [7]
  Jie ZHAO , Sen LIU , Qikang YIN , Xiaoqing LU , Zhaojie WANG . Theoretical calculation of selective adsorption and separation of CO₂ by alkali metal modified naphthalene/naphthalenediyne. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 515-522. doi: 10.11862/CJIC.20230385
8. [8]
  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
9. [9]
  Xiaoning TANG , Shu XIA , Jie LEI , Xingfu YANG , Qiuyang LUO , Junnan LIU , An XUE . Fluorine-doped MnO₂ with oxygen vacancy for stabilizing Zn-ion batteries. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1671-1678. doi: 10.11862/CJIC.20240149
10. [10]
  Tingting Yu , Si Chen , Lianglong Sun , Tongtong Shi , Kai Sun , Xin Wang . Comprehensive Experimental Design for the Photochemical Synthesis, Analysis, and Characterization of Difluoropyrroles. University Chemistry, 2024, 39(11): 196-203. doi: 10.3866/PKU.DXHX202401022
11. [11]
  Yinwu Su , Xuanwen Zheng , Jianghui Du , Boda Li , Tao Wang , Zhiyan Huang . Green Synthesis of 1,3-Dibromoacetone Using Halogen Exchange Method: Recommending a Basic Organic Synthesis Teaching Experiment. University Chemistry, 2024, 39(5): 307-314. doi: 10.3866/PKU.DXHX202311092
12. [12]
  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
13. [13]
  Tianlong Zhang , Rongling Zhang , Hongsheng Tang , Yan Li , Hua Li . Online Monitoring and Mechanistic Analysis of 3,5-diamino-1,2,4-triazole (DAT) Synthesis via Raman Spectroscopy: A Recommendation for a Comprehensive Instrumental Analysis Experiment. University Chemistry, 2024, 39(6): 303-311. doi: 10.3866/PKU.DXHX202312006
14. [14]
  Hong LI , Xiaoying DING , Cihang LIU , Jinghan ZHANG , Yanying RAO . Detection of iron and copper ions based on gold nanorod etching colorimetry. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 953-962. doi: 10.11862/CJIC.20230370
15. [15]
  Tong Zhou , Liyi Xie , Chuyu Liu , Xiyan Zheng , Bao Li . Between Sobriety and Intoxication: The Fascinating Journey of Sauce-Flavored Latte. University Chemistry, 2024, 39(9): 55-58. doi: 10.12461/PKU.DXHX202312048
16. [16]
  Tingbo Wang , Yao Luo , Bingyan Hu , Ruiyuan Liu , Jing Miao , Huizhe Lu . Quantitative Computational Study on the Claisen Rearrangement Reaction of Allyl Phenyl Ethers: An Introduction to a Computational Chemistry Experiment. University Chemistry, 2024, 39(11): 278-285. doi: 10.12461/PKU.DXHX202403082
17. [17]
  Jinfeng Chu , Yicheng Wang , Ji Qi , Yulin Liu , Yan Li , Lan Jin , Lei He , Yufei Song . Comprehensive Chemical Experiment Design: Convenient Preparation and Characterization of an Oxygen-Bridged Trinuclear Iron(III) Complex. University Chemistry, 2024, 39(7): 299-306. doi: 10.3866/PKU.DXHX202310105
18. [18]
  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
19. [19]
  Xin Zhou , Zhi Zhang , Yun Yang , Shuijin Yang . A Study on the Enhancement of Photocatalytic Performance in C/Bi/Bi₂MoO₆ Composites by Ferroelectric Polarization: A Recommended Comprehensive Chemical Experiment. University Chemistry, 2024, 39(4): 296-304. doi: 10.3866/PKU.DXHX202310008
20. [20]
  Ming ZHENG , Yixiao ZHANG , Jian YANG , Pengfei GUAN , Xiudong LI . Energy storage and photoluminescence properties of Sm³⁺-doped Ba_0.85Ca_0.15Ti_0.90Zr_0.10O₃ lead-free multifunctional ferroelectric ceramics. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 686-692. doi: 10.11862/CJIC.20230388

Get Citation

PDF

XML

Metrics

PDF Downloads(15)
Abstract views(1337)
HTML views(169)

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