Synthesis of gem-Difluoroalkenes via Cobalt-Catalyzed Defluorinative Reductive Coupling of α‑Trifluoromethyl Alkenes

doi:10.6023/cjoc202606022

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (9): 3615-3623.DOI: 10.6023/cjoc202606022 Previous Articles Next Articles

ARTICLE

钴催化α-三氟甲基烯烃的脱氟还原偶联反应制备偕二氟烯烃

任慧敏^a^,^b, 茆勇军^a^,^*(), 王子超^b^,^*(), 施世良^b^,^c^,^*()

^a 上海工程技术大学化学工程与工艺重点实验室上海 201620
^b 中国科学院上海有机化学研究所金属有机化学国家重点实验室上海 200032
^c 宁波中科新材料创制中心浙江宁波 315000

收稿日期:2026-06-18 修回日期:2026-07-20 发布日期:2026-08-03
通讯作者: 茆勇军, 王子超, 施世良
基金资助:
国家自然科学基金(22325110); 国家自然科学基金(22401288); 中国科学院战略性先导科技专项(XDB0610000); 中国科学院战略性先导科技专项(XDA0540000); 上海市科学技术委员会项目(24ZR1479000); 与宁波市自然科学基金(2022J017)

Synthesis of gem-Difluoroalkenes via Cobalt-Catalyzed Defluorinative Reductive Coupling of α‑Trifluoromethyl Alkenes

Huimin Ren^a^,^b, Yongjun Mao^a^,^*(), Zichao Wang^b^,^*(), Shiliang Shi^b^,^c^,^*()

^a College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620
^b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032
^c Ningbo Zhongke Creation Center of New Materials, Ningbo, Zhejiang 315000

Received:2026-06-18 Revised:2026-07-20 Published:2026-08-03
Contact: Yongjun Mao, Zichao Wang, Shiliang Shi
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
Supported by:
National Natural Science Foundation of China(22325110); National Natural Science Foundation of China(22401288); Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0610000); Strategic Priority Research Program of the Chinese Academy of Sciences(XDA0540000); Shanghai Science and Technology Committee(24ZR1479000); Ningbo Natural Science Foundation(2022J017)

1. .pdf(2410KB)

Abstract

gem-Difluoroalkenes represent an important class of organic compounds, and the reductive alkylation of α-trifluo- romethyl alkenes serves as a straightforward and efficient synthetic strategy to access these structures. In this work, a ligand- free reductive alkylation of α-trifluoromethyl alkenes was reported using inexpensive cobalt as the catalyst, eliminating the requirement for external supporting ligands. This transformation demonstrates excellent functional group compatibility as well as good tolerance towards heterocyclic moieties, and is compatible with primary, secondary, and tertiary alkyl halide coupling partners. A diverse array of gem-difluoroalkene products was obtained in moderate to excellent yields, and gram-scale experiments further confirm the scalability of this protocol. Overall, this cobalt-catalyzed system features the advantages of practicality and high efficiency for the construction of gem-difluoroalkenes.

Key words: gem-difluoroalkenes, α‑trifluoromethyl alkenes, cobalt catalysis, reductive alkylation

Cite this article

Huimin Ren, Yongjun Mao, Zichao Wang, Shiliang Shi. Synthesis of gem-Difluoroalkenes via Cobalt-Catalyzed Defluorinative Reductive Coupling of α‑Trifluoromethyl Alkenes[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3615-3623.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 5

Scheme 1. (a) Bioactive molecules containing gem-difluoro- alkene scaffolds; (b) Reductive alkylation reaction involving α-trifluoromethyl alkenes; (c) this work

Table 1. Optimization of the reaction conditions

Table 2. Scope of substrates

Scheme 2. Gram-scale reaction and control experiments

Scheme 3. Possible catalytic cycle

References 12

[1]	(a) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529. doi: 10.1021/jm1013693 pmid: 3039140
	(b) Liu, S.; Zhou, J.; Yu, L.; Liu, Y.; Huang, Y.; Ouyang, Y.; Liu, G. K.; Xiu, X. H.; Shibata, N. Chem. Rev. 2025, 125, 4603. doi: 10.1021/acs.chemrev.4c00661 pmid: 3039140
	(c) Bobek, M.; Kavai, I.; De Clercq, E. J. Med. Chem. 1987, 30, 1494. pmid: 3039140
[2]	(a) Fujita, T.; Fuchibe, K.; Ichikawa, J. Angew. Chem. Int. Ed. 2019, 58, 390. doi: 10.1002/anie.v58.2
	(b) Wu, J.-Q.; Zhang, S.-S.; Gao, H.; Qi, Z.; Zhou, C.-J.; Ji, W.-W.; Liu, Y.; Chen, Y.; Li, Q.; Li, X.; Wang, H. J. Am. Chem. Soc. 2017, 139, 3537. doi: 10.1021/jacs.7b00118
	(c) Liu, J.; Yang, J.; Ferretti, F.; Jackstell, R.; Beller, M. Angew. Chem., Int. Ed. 2019, 58, 4690. doi: 10.1002/anie.v58.14
	(d) Liu, C.; Zeng, H.; Zhu, C.; Jiang, H. Chem. Commun. 2020, 56, 10442. doi: 10.1039/D0CC04318D
	(e) Lu, X.; Wang, Y.; Zhang, B.; Pi, J.-J.; Wang, X.-X.; Gong, T.-J.; Xiao, B.; Fu, Y. J. Am. Chem. Soc. 2017, 139, 12632. doi: 10.1021/jacs.7b06469
	(f) Chang, Z.; Yao, C.-Y.; Feng, W.-J.; Zhao, Y.-F. Qian, R.-R.; Hu, X.; Li, Y.; Liu, D.; Lu, X.; Fu, Y. CCS Chem. 2025, 7, 229. doi: 10.31635/ccschem.024.202403958
[3]	(a) Magueur, G.; Crousse, B.; Ourévitch, M.; Bonnet-Delpon, D.; Bégué, J.-P. J. Fluorine Chem. 2006, 127, 637. doi: 10.1016/j.jfluchem.2005.12.013
	(b) Pan, Y.; Qiu, J.; Silverman, R. B. J. Med. Chem. 2003, 46, 5292. doi: 10.1021/jm034162s
	(c) Leriche, C.; He, X.; Chang, C.-W. T.; Liu, H.-W. J. Am. Chem. Soc. 2003, 125, 6348. doi: 10.1021/ja021487+
[4]	(a) Chelucci, G. Chem. Rev. 2012, 112, 1344. doi: 10.1021/cr200165q pmid: 22085400
	(b) Li, S.; Shu, W. Chem. Commun. 2022, 58, 1066. doi: 10.1039/D1CC06446K pmid: 22085400
	(c) Tian, F.; Yan, G.; Yu, J. Chem.Commun. 2019, 55, 13486. pmid: 22085400
[5]	(a) He, Y.; Lv, L.; Jia, Z.; Loh, T. P. Org. Chem. Front. 2026, 13, 2178. doi: 10.1039/D5QO01732G pmid: 35865891
	(b) Zhao, F.; Zhou, W.; Zuo, Z. Adv. Synth. Catal. 2022, 364, 234. doi: 10.1002/adsc.v364.2 pmid: 35865891
	(c) Xiong, W.; Sun, G.; Zhou, M.; Lu, M.; Koh, M. J.; Yang, T. ACS Catal. 2024, 14, 11, 8252. pmid: 35865891
	(d) Guo, Y. Q.; Wang, R.; Song, H.; Liu, Y.; Wang, Q. Org. Lett. 2020, 22, 2, 709. pmid: 35865891
	(e) Lang, S. B.; Wiles, R. J.; Kelly, C. B.; Molander, G. A. Angew. Chem. Int. Ed. 2017, 56, 15073. doi: 10.1002/anie.v56.47 pmid: 35865891
	(f) Shinde, P. S.; Shinde, V. S.; Zhu, C.; Rueping, M. ACS Catal. 2025, 15, 20, 17198. pmid: 35865891
	(g) Bellotti, P.; Huang, H. M.; Faber, T.; Laskar, R.; Glorius, F. Chem. Sci. 2022, 13, 7855. doi: 10.1039/d2sc02732a pmid: 35865891
	(h) Zhang, C.; Wang, L.; Shi, H.; Lin, Z.; Wang, C. Org. Lett. 2022, 24, 3211. doi: 10.1021/acs.orglett.2c00979 pmid: 35865891
	(i) Hu, Q.; Cheng, J.; Wang, Y.; Shi, J.; Wang, B.; Hu, P.; Zhao, K.; Pan, F. Org. Lett. 2021, 23, 4457. doi: 10.1021/acs.orglett.1c01385 pmid: 35865891
	(j) Zhang, C.; Lin, Z.; Zhu, Y.; Wang, C. J. Am. Chem. Soc. 2021, 143, 11602. doi: 10.1021/jacs.1c04531 pmid: 35865891
	(k) Lin, Z.; Lan, Y.; Wang, C. Org. Lett. 2020, 22, 3509. doi: 10.1021/acs.orglett.0c00960 pmid: 35865891
	(l) Yue, W.; Day, C. S.; Martin, R. J. Am. Chem. Soc. 2021, 143, 6395. doi: 10.1021/jacs.1c03126 pmid: 35865891
	(m) Lu, X.; Wang, X.-X.; Gong, T.-J.; Pi, J.-J.; He, S.-J.; Fu, Y. Chem. Sci. 2019, 10, 809. doi: 10.1039/C8SC04335C pmid: 35865891
[6]	(a) Lan, Y.; Yang, F.; Wang, C. ACS Catal. 2018, 8, 9245. doi: 10.1021/acscatal.8b02784
	(b) Lin, Z.; Lan, Y.; Wang, C. Org. Lett. 2019, 21, 8316. doi: 10.1021/acs.orglett.9b03102
[7]	Zhu, C.; Liu, Z. Y.; Tang, L.; Zhang, H.; Zhang, Y. F.; Walsh, P. J.; Feng, C. Nat. Commun. 2020, 11, 4860. doi: 10.1038/s41467-020-18658-4
[8]	Qiu, J.; Wang, C.; Zhou, L.; Lou, Y.; Yang, K.; Song, Q. Org. Lett. 2022, 24, 2446. doi: 10.1021/acs.orglett.2c00800
[9]	(a) Guan, Y. Q.; Wang, T. Z.; Qiao, J. F.; Chen, Z.; Bai, Z.; Liang, Y. F. Chem. Commun. 2022, 58, 13915. doi: 10.1039/D2CC06022A
	(b) Dong, H.; Lin, Z.; Wang, C. Adv. Synth. Catal. 2023, 365, 1165. doi: 10.1002/adsc.v365.8
	(c) Xu, W.; Luo, M.; Zeng, X. Chin. J. Org. Chem. 2025, 45, 3401 (in Chinese). doi: 10.6023/cjoc202505016
	(许文, 罗美明, 曾小明, 有机化学, 2025, 45, 3401.) doi: 10.6023/cjoc202505016
	(d) Fang, Y.; Wang, C. Chin. J. Org. Chem. 2026, 46, 2743 (in Chinese). doi: 10.6023/cjoc202603041
	(房毅, 王川, 有机化学, 2026, 46, 2743.) doi: 10.6023/cjoc202603041
[10]	(a) Yan, X.; Wang, S.; Liu, Z.; Luo, Y.; Wang, P.; Shi, W.; Qi, X.; Huang, Z.; Lei, A. Sci. China Chem. 2022, 65, 762. doi: 10.1007/s11426-021-1210-y
	(b) Zhang, H.; Liang, M.; Zhang, X.; He, M. K.; Yang, C.; Guo, L.; Xia, W. Org. Chem. Front., 2022, 9, 95. doi: 10.1039/D1QO01460A
	(c) Chang, Z.; Wang, J.; Lu, X.; Fu, Y. Chin. J. Org. Chem. 2022, 42, 147 (in Chinese). doi: 10.6023/cjoc202108006
	(常哲, 王佳鑫, 陆熹, 傅尧, 有机化学, 2022, 42, 147.)
	(d) Liu, Y.; Tao, X.; Mao, Y.; Yuan, X.; Qiu, J.; Kong, L.; Ni, S.; Guo, K.; Wang, Y.; Pan, Y. Nat. Commun. 2021, 12, 6745. doi: 10.1038/s41467-021-27060-7
[11]	(a) Cai, Z.; Gu, R.; Si, W.; Xiang, Y.; Sun, J.; Jiao, Y.; Zhang, X. Green Chem. 2022, 24, 6830. doi: 10.1039/D2GC02266D
	(b) Guo, Y.; Cao, Y.; Song, H.; Liu, Y.; Wang, Q. Chem. Commun. 2021, 57, 9768. doi: 10.1039/D1CC04284J
	(c) Yan, S.; Yu, W.; Zhang, J.; Fan, H.; Lu, Z.; Zhang, Z.; Wang, T. J. Org. Chem. 2022, 87, 2, 1574.
	(d) Gladkov, A. A.; Chernov, G. N.; Levin, V. V.; Kokorekin, V. A.; Dilman, A. D. Org. Lett. 2021, 23, 9645. doi: 10.1021/acs.orglett.1c03917
[12]	(a) Wang, Z.-C.; Shi, S.-L. Acc. Chem. Res. 2025, 58, 2157. doi: 10.1021/acs.accounts.5c00304
	(b) Liu, X.-D.; Shi, S.-L. Chin. J. Org. Chem. 2024, 44, 1884 (in Chinese). doi: 10.6023/cjoc202401027
	(刘晓东, 施世良, 有机化学, 2024, 44, 1884.) doi: 10.6023/cjoc202401027
	(c) Wu, H.-Y.; Wang, B.; Wang, Z.-C.; Joo Koh, M.; Shi, S.-L. CCS Chem. 2026, DOI: 10.31635/ccschem.026.202607864.
	(d) Liu, J.-M.; Ma, X.; Chen, G.; Wan, W.; Li, Z.; Xu, Y.; Zhang, D.; Shi, S.-L. Sci. Bull. 2025, 70, 674. doi: 10.1016/j.scib.2024.12.023
	(e) Lu, J.; Ruan, L.-X.; Shi, S.-L. Chin. Sci. Bull. 2025, DOI: 10.1360/CSB-2025-5189.

钴催化α-三氟甲基烯烃的脱氟还原偶联反应制备偕二氟烯烃

Synthesis of gem-Difluoroalkenes via Cobalt-Catalyzed Defluorinative Reductive Coupling of α‑Trifluoromethyl Alkenes

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 12

Related Articles 10

Recommended Articles

Metrics

Comments

[1]	Jinquan Chen, Peiqiang Huang. Application of Amide Reductive Alkynylation and Reductive Alkylation in the Rapid Synthesis of Schwarzinicines A~C and Ficusnotins B, F [J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3646-3658.
[2]	Qian Xiao, Jian-Ji Zhong. Recent Advances in Cobalt-Catalysis for C—S Bond Construction [J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2644-2668.
[3]	Rutong Ren, Shichao Lu, Hongshuang Li. Earth-Abundant Cobalt-Catalyzed Alkene Hydroacylation [J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2701-2712.
[4]	Rundong Fan, Bingran Chen, Fuqi Li, Jinxiu Chen, Qiongjiao Yan, Wei Wang, Hui Zhou. Photosensitizer-Free Photoinduced Hydrodifluoroalkylation of α‑Trifluoromethyl Alkenes [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 641-652.
[5]	Zhanxiang Liu, Chao Hong, Siyuan Li, Shengru Huang, Ningxia Zhang, Ruokun Feng, Yuhong Zhang. Synthesis of 2,4,6-Trisubstituted Pyridines via Cobalt-Catalyzed Homocoupling of α,β-Unsaturated Ketone Oxime Esters [J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3777-3785.
[6]	Jiayan Du, Juntao Liu, Guixia Liu, Zheng Huang. Cobalt-Catalyzed Regio- and Stereoselective Isomerization of Terminal Alkenes to trans-2-Alkenes [J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2889-2897.
[7]	Qin Shi, Zhen Li, Lin He, Yudong Li, Yuehui Li. Boron-Promoted Co-Catalyzed N-Methylation of Secondary Aromatic Amines with CO₂ and H₂ [J]. Chinese Journal of Organic Chemistry, 2024, 44(10): 3233-3240.
[8]	Shiquan Gao, Chuangjun Liu, Junfeng Yang, Junliang Zhang. Cobalt-Catalyzed Electrochemical Reductive Coupling of Alkynes and Alkenes [J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1559-1565.
[9]	Yinyin Wang, Xiaowan Lin, Piao Zhang, Meihua Shen, Huadong Xu, Defeng Xu. Design and Synthesis of Pyridine and 1,3,5-Triazine PNP Pincer Ligands and Their Application in Cobalt Catalyzed Semihydrogenation of Terminal Alkynes [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3312-3320.
[10]	Sun Yiming, Ding Qifeng, Yu Yang, He Yide, Huang Fei. Progress in Co-Catalyzed C-H Amination [J]. Chinese Journal of Organic Chemistry, 2019, 39(12): 3363-3374.