Citation: Junqi Su, Wenhao Liu, Jianjun Wang, Weifen Luo, Yangyang Ma, Leiyang Lv, Zhiping Li. Palladium-catalyzed ring-opening defluorinative cross-coupling of gem-difluorocyclopropanes with fluoromalonates or fluorobis(phenylsulfonyl)methane[J]. Chinese Chemical Letters, ;2026, 37(3): 111288. doi: 10.1016/j.cclet.2025.111288 shu

Palladium-catalyzed ring-opening defluorinative cross-coupling of gem-difluorocyclopropanes with fluoromalonates or fluorobis(phenylsulfonyl)methane

Junqi Su ^a ,
Wenhao Liu ^a ,
Jianjun Wang ^b ,
Weifen Luo ^b ,
Yangyang Ma ^c ,
Leiyang Lv ^{a, *,} ,
Zhiping Li ^{a, *,}

a.
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, School of Chemistry and Life Resources, Renmin University of China, Beijing 100872, China
b.
Fujian Yongjing Technology Co., Ltd., Shaowu 354003, China
c.
College of Chemistry and Environmental Engineering, Pingdingshan University, Pingdingshan 467000, China

lvleiyang2020@ruc.edu.cn

zhipingli@ruc.edu.cn

Received Date: 14 March 2025
Revised Date: 24 April 2025
Accepted Date: 7 May 2025
Available Online: 8 May 2025

Figures(4)

Fluorine locates a pivotal position in modern medicinal chemistry due to its distinctive impact on the properties of organic molecules. This work described an efficient divergent palladium/XPhos-catalyzed ring-opening defluorinative cross-coupling of gem-difluorocyclopropanes with less nucleophilic fluorinated malonates or fluorobis(phenylsulfonyl)methane. The corresponding difluoro malonates and 2,4-difluorobutadienyl sulfones were obtained in good yields, respectively. Besides, this protocol also enabled the modification of structurally diverse complex molecules.
- gem-difluorocyclopropanes,
- C-F cleavage,
- Pd catalysis,
- Ring-opening,
- Fluoromalonates
1. [1]
  D. O'Hagan, Chem. Soc. Rev. 37 (2008) 308–319. doi: 10.1039/B711844A
2. [2]
  E.P. Gillis, K.J. Eastman, M.D. Hill, D.J. Donnelly, N.A. Meanwell, J. Med. Chem. 58 (2015) 8315–8359. doi: 10.1021/acs.jmedchem.5b00258
3. [3]
  Q. Wang, H. Song, Q. Wang, Chin. Chem. Lett. 33 (2022) 626–642. doi: 10.1016/j.cclet.2021.07.064
4. [4]
  D. Ge, X.Q. Chu, Org. Chem. Front. 9 (2022) 2013–2055. doi: 10.1039/d1qo01749g
5. [5]
  J.D. Hamel, J.F. Paquin, Chem. Commun. 54 (2018) 10224–10239. doi: 10.1039/c8cc05108a
6. [6]
  T. Stahl, H.F.T. Klare, M. Oestreich, ACS Catal. 3 (2013) 1578–1587. doi: 10.1021/cs4003244
7. [7]
  J.L. Kiplinger, T.G. Richmond, C.E. Osterberg, Chem. Rev. 94 (1994) 373–431. doi: 10.1021/cr00026a005
8. [8]
  T. Ahrens, J. Kohlmann, M. Ahrens, T. Braun, Chem. Rev. 115 (2015) 931–972. doi: 10.1021/cr500257c
9. [9]
  T. Fujita, K. Fuchibe, J. Ichikawa, Angew. Chem. Int. Ed. 58 (2019) 390–402. doi: 10.1002/anie.201805292
10. [10]
  K. Chen, N. Berg, R. Gschwind, B. König, J. Am. Chem. Soc. 139 (2017) 18444–18447. doi: 10.1021/jacs.7b10755
11. [11]
  Y.C. Luo, F.F. Tong, Y. Zhang, C.Y. He, X. Zhang, J. Am. Chem. Soc. 143 (2021) 13971–13979. doi: 10.1021/jacs.1c07459
12. [12]
  Y.J. Yu, F.L. Zhang, T.Y. Peng, et al., Science 371 (2021) 1232–1240. doi: 10.1126/science.abg0781
13. [13]
  K. Lye, R.D. Young, Chem. Sci. 15 (2024) 2712–2724. doi: 10.1039/d3sc06485a
14. [14]
  H. Amii, K. Uneyama, Chem. Rev. 109 (2009) 2119–2183. doi: 10.1021/cr800388c
15. [15]
  D.B. Vogt, C.P. Seath, H. Wang, N.T. Jui, J. Am. Chem. Soc. 141 (2019) 13203–13211. doi: 10.1021/jacs.9b06004
16. [16]
  G. Landelle, M. Bergeron, M.O. Turcotte-Savard, J.F. Paquin, Chem. Soc. Rev. 40 (2011) 2867–2908. doi: 10.1039/c0cs00201a
17. [17]
  G. Yan, K. Qiu, M. Guo, Org. Chem. Front. 8 (2021) 3915–3942. doi: 10.1039/d1qo00037c
18. [18]
  T.W. Butcher, J.L. Yang, W.M. Amberg, et al., Nature 583 (2020) 548–553. doi: 10.1038/s41586-020-2399-1
19. [19]
  W.R. Dolbier, M.A. Battiste, Chem. Rev. 103 (2003) 1071–1098. doi: 10.1021/cr010023b
20. [20]
  M. Fedoryński, Chem. Rev. 103 (2003) 1099–1132. doi: 10.1021/cr0100087
21. [21]
  K.S. Adekenova, P.B. Wyatt, S.M. Adekenov, Beilstein J. Org. Chem. 17 (2021) 245–272. doi: 10.3762/bjoc.17.25
22. [22]
  L. Lv, J. Su, Z. Li, Org. Chem. Front. 11 (2024) 6518–6533. doi: 10.1039/d4qo01583e
23. [23]
  L. Lv, H. Qian, Z. Li, ChemCatChem 14 (2022) e202200890. doi: 10.1002/cctc.202200890
24. [24]
  Y. Zhu, Y. Zeng, Z.T. Jiang, Y. Xia, Synlett 34 (2023) 1–13.
25. [25]
  Y. Zeng, Z.T. Jiang, Y. Xia, Chem. Commun. 60 (2024) 3764–3773. doi: 10.1039/d4cc00793j
26. [26]
  J. Xu, E.A. Ahmed, B. Xiao, et al., Angew. Chem. Int. Ed. 54 (2015) 8231–8235. doi: 10.1002/anie.201502308
27. [27]
  E.A.M.A. Ahmed, A.M.Y. Suliman, T.J. Gong, Y. Fu, Org. Lett. 22 (2020) 1414–1419. doi: 10.1021/acs.orglett.0c00022
28. [28]
  Z. Fu, J. Zhu, S. Guo, A. Lin, Chem. Commun. 57 (2021) 1262–1265. doi: 10.1039/d0cc07529a
29. [29]
  W. Yuan, X. Li, Z. Qi, X. Li, Org. Lett. 24 (2022) 2093–2098. doi: 10.1021/acs.orglett.2c00246
30. [30]
  L. Wu, M. Wang, Y. Liang, Z. Shi, Chin. J. Chem. 40 (2022) 2345–2355. doi: 10.1002/cjoc.202200307
31. [31]
  Z.T. Jiang, J. Huang, Y. Zeng, F. Hu, Y. Xia, Angew. Chem. Int. Ed. 60 (2021) 10626–10631. doi: 10.1002/anie.202016258
32. [32]
  Y. Xia, J. Jia, Chin. J. Org. Chem. 43 (2023) 4017–4018. doi: 10.6023/cjoc202300065
33. [33]
  Y. Zeng, H. Gao, Z.T. Jiang, et al., Nat. Commun. 15 (2024) 4317. doi: 10.1038/s41467-024-48541-5
34. [34]
  Y. Zeng, Y. Xia, Chin. J. Org. Chem. 43 (2023) 3331–3333. doi: 10.6023/cjoc202300052
35. [35]
  Z. Su, B. Tan, H. He, et al., Angew. Chem. Int. Ed. 63 (2024) e202402038. doi: 10.1002/anie.202402038
36. [36]
  Z. Wang, C. Liu, J. Huang, L. Huang, H. Feng, Org. Lett. 26 (2024) 6905–6909. doi: 10.1021/acs.orglett.4c02554
37. [37]
  Y. Yan, W. Lu, H. Qian, L. Lv, Z. Li, Chin. J. Org. Chem. 44 (2024) 1630–1640. doi: 10.6023/cjoc202312003
38. [38]
  X. Zhang, H. Lin, B. Tan, et al., Org. Lett. 26 (2024) 8956–8960. doi: 10.1021/acs.orglett.4c03477
39. [39]
  J. Ni, B. Nishonov, A. Pardaev, A. Zhang, J. Org. Chem. 84 (2019) 13646– 13654. doi: 10.1021/acs.joc.9b01897
40. [40]
  D. Li, C. Shen, Z. Si, L. Liu, Angew. Chem. Int. Ed. 62 (2023) e202310283. doi: 10.1002/anie.202310283
41. [41]
  Y. Zhu, J. Jia, X. Song, C. Gong, Y. Xia, Chem. Sci. 15 (2024) 13800–13806. doi: 10.1039/d4sc03624g
42. [42]
  Z. Liang, H. Ye, H. Zhang, G. Jiang, X. Wu, Chin. J. Org. Chem. 43 (2023) 1483–1491. doi: 10.6023/cjoc202208031
43. [43]
  B. Xiong, X. Chen, J. Liu, et al., ACS Catal. 11 (2021) 11960–11965. doi: 10.1021/acscatal.1c02952
44. [44]
  X. Qi, F. Yuan, X. Yan, Y. Xia, Org. Lett. 26 (2024) 10317–10321. doi: 10.1021/acs.orglett.4c03920
45. [45]
  H. Yang, Y. Zeng, X. Song, et al., Angew. Chem. Int. Ed. 63 (2024) e202403602. doi: 10.1002/anie.202403602
46. [46]
  Y. Zeng, Y. Xia, Angew. Chem. Int. Ed. 62 (2023) e202307129. doi: 10.1002/anie.202307129
47. [47]
  B. Zhao, Z. Pan, J. Pan, et al., Green Chem. 25 (2023) 3095–3102. doi: 10.1039/d2gc04636a
48. [48]
  T.S. Wu, Y.J. Hao, Z.J. Cai, S.J. Ji, Org. Chem. Front. 11 (2024) 1057–1061. doi: 10.1039/d3qo01879b
49. [49]
  Z. Su, B. Tan, Z. Li, H. Huang, Y. Zhang, Org. Lett. 26 (2024) 5375–5379. doi: 10.1021/acs.orglett.4c01882
50. [50]
  L. Lv, C.J. Li, Angew. Chem. Int. Ed. 60 (2021) 13098–13104. doi: 10.1002/anie.202102240
51. [51]
  L. Lv, H. Qian, A.B. Crowell, S. Chen, Z. Li, ACS Catal. 12 (2022) 6495–6505. doi: 10.1021/acscatal.2c01391
52. [52]
  H. Qian, H.D. Nguyen, L. Lv, S. Chen, Z. Li, Angew. Chem. Int. Ed. 62 (2023) e202303271. doi: 10.1002/anie.202303271
53. [53]
  H. Qian, Z.P. Cheng, Y. Luo, et al., J. Am. Chem. Soc. 146 (2024) 24–32. doi: 10.1021/jacs.3c07992
54. [54]
  L. Lv, H. Qian, Y. Ma, et al., Chem. Sci. 12 (2021) 15511–15518. doi: 10.1039/d1sc05451a
55. [55]
  Y. Yan, H. Qian, L. Lv, Z. Li, J. Org. Chem. 89 (2024) 16253–16261. doi: 10.1021/acs.joc.3c00744
56. [56]
  J. Saadi, H. Wennemers, Nat. Chem. 8 (2016) 276–280. doi: 10.1038/nchem.2437
57. [57]
  Y. Lv, W. Pu, X. Zhu, C. Chen, S. Wang, J. Org. Chem. 86 (2021) 10043–10054. doi: 10.1021/acs.joc.1c00789
58. [58]
  B. Huang, C. Li, H. Wang, et al., Org. Lett. 19 (2017) 5102–5105. doi: 10.1021/acs.orglett.7b02365
59. [59]
  Z.W. Hou, T. Jiang, T.X. Wu, L. Wang, Org. Lett. 23 (2021) 8585–8589. doi: 10.1021/acs.orglett.1c03284
60. [60]
  H. Jiang, W.W. Zhao, X. Wang, et al., Chem. Eur. J. 30 (2024) e202402875. doi: 10.1002/chem.202402875
61. [61]
  M. Chen, Z.J. Wu, J. Song, H.C. Xu, Angew. Chem. Int. Ed. 61 (2022) e202115954. doi: 10.1002/anie.202115954
62. [62]
  Q.Y. Liao, C. Ma, Y.C. Wang, et al., Chin. Chem. Lett. 34 (2023) 108371. doi: 10.1016/j.cclet.2023.108371
63. [63]
  X. Wang, H.Z. Miao, G.Q. Lin, Z.T. He, Angew. Chem. Int. Ed. 62 (2023) e202301556. doi: 10.1002/anie.202301556
64. [64]
  Z.W. Hou, T. Jiang, T.X. Wu, L. Wang, Org. Lett. 23 (2021) 8585–8589. doi: 10.1021/acs.orglett.1c03284
65. [65]
  A. Harsanyi, G. Sandford, Org. Process Res. Dev. 18 (2014) 981–992. doi: 10.1021/op500141c
66. [66]
  T. Furukawa, N. Shibata, S. Mizuta, et al., Angew. Chem. Int. Ed. 47 (2008) 8051–8054. doi: 10.1002/anie.200802904
67. [67]
  S. Mizuta, N. Shibata, Y. Goto, et al., J. Am. Chem. Soc. 129 (2007) 6394–6395. doi: 10.1021/ja071509y
68. [68]
  G.K.S. Prakash, S. Chacko, S. Alconcel, et al., Angew. Chem. Int. Ed. 46 (2007) 4933–4936. doi: 10.1002/anie.200700834
69. [69]
  T. Fukuzumi, N. Shibata, M. Sugiura, et al., Angew. Chem. Int. Ed. 45 (2006) 4973–4977. doi: 10.1002/anie.200600625
70. [70]
  X. Shen, L. Zhang, Y. Zhao, et al., Angew. Chem. Int. Ed. 50 (2011) 2588–2592. doi: 10.1002/anie.201006931
71. [71]
  S.L. Zhang, H.X. Xie, J. Zhu, et al., Nat. Commun. 2 (2011) 211. doi: 10.1038/ncomms1214
72. [72]
  G.K.S. Prakash, S. Chacko, H. Vaghoo, et al., Org. Lett. 11 (2009) 1127–1130. doi: 10.1021/ol8029627
73. [73]
  X.Q. Chu, D. Ge, Y.Y. Cui, Z.L. Shen, C.J. Li, Chem. Rev. 121 (2021) 12548–12680. doi: 10.1021/acs.chemrev.1c00084
74. [74]
  Y. Li, X. Li, X. Li, D. Shi, J. Org. Chem. 86 (2021) 6983–6993. doi: 10.1021/acs.joc.1c00490
75. [75]
  F. Zhu, P.W. Xu, F. Zhou, C.H. Wang, J. Zhou, Org. Lett. 17 (2015) 972–975. doi: 10.1021/acs.orglett.5b00072
1. [1]
  Yue Sun , Liming Yang , Yaohang Cheng , Guanghui An , Guangming Li . Pd(I)-catalyzed ring-opening arylation of cyclopropyl-α-aminoamides: Access to α-ketoamide peptidomimetics. Chinese Chemical Letters, 2024, 35(6): 109250-. doi: 10.1016/j.cclet.2023.109250
2. [2]
  Rong-Nan Yi , Wei-Min He . Visible light/copper catalysis enabled radial type ring-opening of sulfonium salts. Chinese Chemical Letters, 2025, 36(4): 110787-. doi: 10.1016/j.cclet.2024.110787
3. [3]
  Qinghong Zhang , Qiao Zhao , Xiaodi Wu , Li Wang , Kairui Shen , Yuchen Hua , Cheng Gao , Yu Zhang , Mei Peng , Kai Zhao . Visible-light-induced ring-opening cross-coupling of cycloalcohols with vinylazaarenes and enones via β-C-C scission enabled by proton-coupled electron transfer. Chinese Chemical Letters, 2025, 36(2): 110167-. doi: 10.1016/j.cclet.2024.110167
4. [4]
  Feng Zhao , Hongyu Ding , Ting Sun , Chao Shen , Zu-Li Wang , Wei Wei , Dong Yi . Visible-light-promoted multi-component carbene transfer reactions of diazo compounds via ring-opening of cyclic ethers. Chinese Chemical Letters, 2026, 37(2): 111834-. doi: 10.1016/j.cclet.2025.111834
5. [5]
  Dong-Sheng Deng , Su-Qin Tang , Yong-Tu Yuan , Ding-Xiong Xie , Zhi-Yuan Zhu , Yue-Mei Huang , Yun-Lin Liu . C-F insertion reaction sheds new light on the construction of fluorinated compounds. Chinese Chemical Letters, 2024, 35(8): 109417-. doi: 10.1016/j.cclet.2023.109417
6. [6]
  Xiaoyu Zhao , Kai Gao , Sen Xue , Wei Ran , Rui Liu . Synergistic effects of oxygen vacancies and Pd single atoms on Pd@TiO_2−x for efficient HER catalysis. Chinese Chemical Letters, 2025, 36(6): 110309-. doi: 10.1016/j.cclet.2024.110309
7. [7]
  Haoran Shi , Jiaxin Wang , Yuqin Zhu , Hongyang Li , Guodong Ju , Lanlan Zhang , Chao Wang . Highly selective α-C(sp³)-H arylation of alkenyl amides via nickel chain-walking catalysis. Chinese Chemical Letters, 2024, 35(7): 109333-. doi: 10.1016/j.cclet.2023.109333
8. [8]
  Xiao-Hua Chen , Yifan Fan , Zitong Wu , Tao Tu . Non-canonical bio-inspired iron catalysis for aliphatic C–H functionalization. Chinese Chemical Letters, 2026, 37(3): 112132-. doi: 10.1016/j.cclet.2025.112132
9. [9]
  Peiyan Zhu , Yanyan Yang , Hui Li , Jinhua Wang , Shiqing Li . Rh(Ⅲ)‐Catalyzed sequential ring‐retentive/‐opening [4 + 2] annulations of 2H‐imidazoles towards full‐color emissive imidazo[5,1‐a]isoquinolinium salts and AIE‐active non‐symmetric 1,1′‐biisoquinolines. Chinese Chemical Letters, 2024, 35(10): 109533-. doi: 10.1016/j.cclet.2024.109533
10. [10]
  Yi Luo , Lin Dong . Multicomponent remote C(sp²)-H bond addition by Ru catalysis: An efficient access to the alkylarylation of 2H-imidazoles. Chinese Chemical Letters, 2024, 35(10): 109648-. doi: 10.1016/j.cclet.2024.109648
11. [11]
  Xiangyang Ji , Yishuang Chen , Peng Zhang , Shaojia Song , Jian Liu , Weiyu Song . Boosting the first C–H bond activation of propane on rod-like V/CeO₂ catalyst by photo-assisted thermal catalysis. Chinese Chemical Letters, 2025, 36(5): 110719-. doi: 10.1016/j.cclet.2024.110719
12. [12]
  Yuhan Zhang , Xiao-Lin Zhang , Han Ding , Yuan Xu , Xue-Wei Liu . Catalytic ring-strain release toward a facial and efficient synthesis of versatile C-glycosides. Chinese Chemical Letters, 2025, 36(7): 110560-. doi: 10.1016/j.cclet.2024.110560
13. [13]
  Junhua Li , Yu Fu , Yian Shi . A rapid access to fused polycyclic indolo[2,1-a]isoquinolins via Pd-catalyzed sequential Heck/C-H activation/amination reaction with diaziridinone. Chinese Chemical Letters, 2026, 37(3): 111376-. doi: 10.1016/j.cclet.2025.111376
14. [14]
  Jialin Huang , Liying Fu , Zhanyong Tang , Xiaoqiang Ma , Xingda Zhao , Depeng Zhao . Cross-coupling of trifluoromethylarenes with alkynes C(sp)-H bonds and azoles C(sp²)-H bonds via photoredox/copper dual catalysis. Chinese Chemical Letters, 2025, 36(7): 110505-. doi: 10.1016/j.cclet.2024.110505
15. [15]
  Mengyu Wu , Kewei Ren , Chengyu Zou , Jiacheng Chen , Rui Ma , Chuan Zhu , Chao Feng . A general synthesis of gem–difluorobicyclo[2.1.1]hexanes. Chinese Chemical Letters, 2025, 36(5): 110213-. doi: 10.1016/j.cclet.2024.110213
16. [16]
  Conghui Wang , Lei Xu , Zhenhua Jia , Teck-Peng Loh . Recent applications of macrocycles in supramolecular catalysis. Chinese Chemical Letters, 2024, 35(4): 109075-. doi: 10.1016/j.cclet.2023.109075
17. [17]
  Wei Chen , Pieter Cnudde . A minireview to ketene chemistry in zeolite catalysis. Chinese Journal of Structural Chemistry, 2024, 43(11): 100412-100412. doi: 10.1016/j.cjsc.2024.100412
18. [18]
  Lin Zhang , Chaoran Li , Thongthai Witoon , Xingda An , Le He . Nano-thermometry in photothermal catalysis. Chinese Journal of Structural Chemistry, 2025, 44(4): 100456-100456. doi: 10.1016/j.cjsc.2024.100456
19. [19]
  Zhen Liu , Zhi-Yuan Ren , Chen Yang , Xiangyi Shao , Li Chen , Xin Li . Asymmetric alkenylation reaction of benzoxazinones with diarylethylenes catalyzed by B(C₆F₅)₃/chiral phosphoric acid. Chinese Chemical Letters, 2024, 35(5): 108939-. doi: 10.1016/j.cclet.2023.108939
20. [20]
  Jun Jiang , Hui Dai , Tao Tu . Two vicinal C(sp³)-F bonds functionalization of perfluoroalkyl halides (PFAHs). Chinese Chemical Letters, 2025, 36(7): 111054-. doi: 10.1016/j.cclet.2025.111054

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(18)
HTML views(1)

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