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

doi:10.6023/A18080314

Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (12): 977-982.DOI: 10.6023/A18080314 Previous Articles Next Articles

Special Issue: 有机氟化学

Communication

铁催化下二芳基锌和芳基格氏试剂的二氟烷基化反应

安伦, 童非非, 张新刚

中国科学院上海有机化学研究所分子合成卓越中心中国科学院有机氟化学重点实验室上海 200032

投稿日期:2018-09-18 发布日期:2018-12-11
通讯作者: 张新刚,E-mail:xgzhang@sioc.ac.cn,Tel.:021-54925333,Fax:021-64166128 E-mail:xgzhang@sioc.ac.cn
基金资助:
项目受国家重点基础研究发展计划（973计划）（No.2015CB931900）、国家自然科学基金（Nos.21425208，21672238，21332010，21421002）和中国科学院先导专项（No.XDB20000000）资助.

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

An Lun, Tong Feifei, Zhang Xingang

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

Received:2018-09-18 Published:2018-12-11
Contact: 10.6023/A18080314 E-mail:xgzhang@sioc.ac.cn
Supported by:
Project 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).

1. Iron-Catalyzed Cross-Coupling of Diarylzinc or Aryl Grignard Reagents with Difluoroalkyl Bromides.PDF(3678KB)

Abstract

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.

Key words: iron, diarylzinc reagents, gem-difluoropropargyl bromide, cross-coupling

Cite this article

An Lun, Tong Feifei, Zhang Xingang. Iron-Catalyzed Cross-Coupling of Diarylzinc or Aryl Grignard Reagents with Difluoroalkyl Bromides[J]. Acta Chim. Sinica, 2018, 76(12): 977-982.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[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] (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] 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] 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] (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] 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] 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] (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] (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] (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] 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.; Knölker, 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] 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] An, L.; Xiao, Y.-L.; Zhang, X. Angew. Chem., Int. Ed. 2018, 57, 6921.
[14] Xu, B.; Mashuta, M. S.; Hammond, G. B. Angew. Chem., Int. Ed. 2006, 45, 7265.
[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] (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] (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] (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.

铁催化下二芳基锌和芳基格氏试剂的二氟烷基化反应

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

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Dawei Zhang, Haiyang Zhao, Xiaotian Feng, Yucheng Gu, Xingang Zhang. Palladium-Catalyzed Cross-Coupling of Heteroaryl Bromides with gem-Difluoroallylborons [J]. Acta Chimica Sinica, 2024, 82(2): 105-109.
[2]	Yujie Yang, Yuxiu Gong, Tianhang Gu, Wei-xian Zhang. Progress and Environmental Research Applications of Cryo-Electron Microscopy^★ [J]. Acta Chimica Sinica, 2023, 81(8): 990-1001.
[3]	Zeng Chongyang, Hu Ping, Wang Biqin, Fang Wenyan, Zhao Keqing, Donnio Bertrand. Star-shaped Triphenylene-triazine Multi-stimuli Responsive Discotic Liquid Crystals: Synthesis, Properties and Applications [J]. Acta Chimica Sinica, 2023, 81(5): 469-479.
[4]	Junliang Zhou, Zhenxin Zhao, Tingyi Wu, Xiaomin Wang. Efficient Catalytic Conversion of Polysulfides in Multifunctional FeP/Carbon Cloth Interlayer for High Capacity and Stability of Lithium-sulfur Batteries [J]. Acta Chimica Sinica, 2023, 81(4): 351-358.
[5]	Mingliang Han, Lihua Xu. Progress on the Transition Metal-catalyzed Cross-coupling Reaction of Thioesters [J]. Acta Chimica Sinica, 2023, 81(4): 381-392.
[6]	Guanglu Yue, Jingyao Wei, Di Qiu, Fanyang Mo. Recent Advances in the Synthesis of Arylstannanes [J]. Acta Chimica Sinica, 2022, 80(7): 956-969.
[7]	Xuezhi Yang, Dawei Lu, Weichao Wang, Hang Yang, Qian Liu, Guibin Jiang. Nano-Tracing: Recent Progress in Sourcing Tracing Technology of Nanoparticles^※ [J]. Acta Chimica Sinica, 2022, 80(5): 652-658.
[8]	Qinghao Xu, Lipu Wei, Zhen Zhang, Bin Xiao. Copper Promoted Synthesis of Tetraalkylgermanes from Germanium Electrophiles and Alkyl Bromides^※ [J]. Acta Chimica Sinica, 2022, 80(4): 428-431.
[9]	Shangzhao Li, Zhenwu Ouyang, Junjie Zou, Dongyang Wang, Bin Xu, Liang Deng. A Mononuclear Iron Thiolate Complex with N-Heterocyclic Carbene Ligation [J]. Acta Chimica Sinica, 2022, 80(3): 272-276.
[10]	Siming Yang, Airong Liu, Jing Liu, Zhaoli Liu, Weixian Zhang. Advance of Sulfidated Nanoscale Zero-Valent Iron: Synthesis, Properties and Environmental Application [J]. Acta Chimica Sinica, 2022, 80(11): 1536-1554.
[11]	Zhuhan Zhang, Fengjing Jiang, Keke Wu, Peng Shen. Research on Iron-Lead Semi-Flow Battery Based on 3D Solid Electrode [J]. Acta Chimica Sinica, 2022, 80(1): 56-62.
[12]	Yilong Hua, Donghan Li, Tianhang Gu, Wei Wang, Ruofan Li, Jianping Yang, Wei-xian Zhang. Enrichment of Uranium from Aqueous Solutions with Nanoscale Zero-valent Iron: Surface Chemistry and Application Prospect [J]. Acta Chimica Sinica, 2021, 79(8): 1008-1022.
[13]	Xiaobiao Lu, Xi Xiao, Changfeng Wan, Zhiyong Wang, Jinbiao Liu. Direct C—C Bond Formation through Decarboxylative Oxidative Cross-Coupling of Cinnamic Acids with Amides under Metal-Free Condition [J]. Acta Chimica Sinica, 2021, 79(6): 751-754.
[14]	Zheng Cai, Yingwen Zhang, Liping Jiang, Junjie Zhu. The Construction and Application of Mn₃O₄/DOX@Lip Nano-drug Delivery System Based on Fenton-Like Reaction [J]. Acta Chimica Sinica, 2021, 79(4): 481-489.
[15]	Xue-Min Zhu, Xiao-Yan Bai, Hai-Feng Wang, Ping Hu, Bi-Qin Wang, Ke-Qing Zhao. Benzo[g]chrysene Discotic Liquid Crystals: Synthesis, Columnar Mesophase and Photophysical Properties [J]. Acta Chimica Sinica, 2021, 79(12): 1486-1493.