Citation: Jing Zhang, Chen-Fei Gao, Xin-Shan Ye, De-Cai Xiong. Electrochemical α-glycosylation of exo-glycals[J]. Chinese Chemical Letters, ;2026, 37(9): 112200. doi: 10.1016/j.cclet.2025.112200 shu

Electrochemical α-glycosylation of exo-glycals

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

decai@bjmu.edu.cn

Received Date: 8 September 2025
Revised Date: 18 November 2025
Accepted Date: 28 November 2025
Available Online: 1 December 2025

Figures(3)

Electrosynthesis has emerged as a powerful and sustainable strategy in organic chemistry, with growing applications in carbohydrate synthesis. Herein, we report an electrochemical method for the regio- and stereo-selective O-glycosylation of exo-glycals with a wide range of substrates under mild conditions. This approach employs simple setup in an undivided cell with KOTf as electrolyte, facilitating the efficient synthesis of bioactive O-glycosides in good yields and with exclusive α-selectivity. The reaction exhibits broad substrate compatibility, accommodating both sugar- and non-sugar-based acceptors, including complex natural products and pharmaceuticals. Furthermore, gram-scale reactions proceed without loss of efficiency or stereocontrol, underscoring the practicality of this method. Mechanistic studies suggest a radical cation-based pathway. This strategy provides a robust and scalable platform for O-glycosides synthesis.
- Exo-glycals,
- 1′-C-methyl-O-glycosides,
- Stereoselectivity,
- Electrocatalysis,
- Glycosylation
1. [1]
  S.C. Ranade, A.V. Demchenko, J. Carbohydr. Chem. 32 (2013) 1–43.
2. [2]
  K.T. Schjoldager, Y. Narimatsu, H.J. Joshi, et al., Nat. Rev. Mol. Cell Biol. 21 (2020) 729–749. doi: 10.1038/s41580-020-00294-x
3. [3]
  A. Varki, Glycobiology 27 (2016) 3–49.
4. [4]
  Y.D. Vankar, R.R. Schmidt, Chem. Soc. Rev. 29 (2000) 201–216. doi: 10.1039/a900943d
5. [5]
  F. Pfrengle, H.U. Reissig, Chem. Soc. Rev. 39 (2010) 549–557. doi: 10.1039/B914356D
6. [6]
  W. Li, B. Yu, Chem. Soc. Rev. 47 (2018) 7954–7984. doi: 10.1039/C8CS00209F
7. [7]
  A. Tamburrini, C. Colombo, A. Bernardi, Med. Res. Rev. 40 (2020) 495–531. doi: 10.1002/med.21625
8. [8]
  R. Francke, R.D. Little, Chem. Soc. Rev. 43 (2014) 2492–2521. doi: 10.1039/c3cs60464k
9. [9]
  Y. Li, S. Dana, L. Ackermann, Curr. Opin. Electrochem. 40 (2023) 101312. doi: 10.1016/j.coelec.2023.101312
10. [10]
  N. Fu, G.S. Sauer, S. Lin, Nat. Protoc. 13 (2018) 1725–1743. doi: 10.1038/s41596-018-0010-0
11. [11]
  J.E. Nutting, M. Rafiee, S.S. Stahl, Chem. Rev. 118 (2018) 4834–4885. doi: 10.1021/acs.chemrev.7b00763
12. [12]
  J.C. Siu, N. Fu, S. Lin, Acc. Chem. Res. 53 (2020) 547–560. doi: 10.1021/acs.accounts.9b00529
13. [13]
  L. Song, N. Fu, B.G. Ernst, et al., Nat. Chem. 12 (2020) 747–754. doi: 10.1038/s41557-020-0469-5
14. [14]
  L.F.T. Novaes, J. Liu, Y. Shen, et al., Chem. Soc. Rev. 50 (2021) 7941–8002. doi: 10.1039/D1CS00223F
15. [15]
  C. Zhu, N.W.J. Ang, T.H. Meyer, et al., ACS Cent. Sci. 7 (2021) 415–431. doi: 10.1021/acscentsci.0c01532
16. [16]
  C.A. Malapit, M.B. Prater, J.R. Cabrera-Pardo, et al., Chem. Rev. 122 (2022) 3180–3218. doi: 10.1021/acs.chemrev.1c00614
17. [17]
  M.C. Lamb, K.A. Steiniger, L.K. Trigoura, et al., Chem. Rev. 124 (2024) 12264–12304. doi: 10.1021/acs.chemrev.4c00464
18. [18]
  R.R. France, R.G. Compton, B.G. Davis, et al., Org. Biomol. Chem. 2 (2004) 2195–2202. doi: 10.1039/b316728c
19. [19]
  S. Manmode, K. Matsumoto, T. Nokami, et al., Asian J. Org. Chem. 7 (2018) 1719–1729. doi: 10.1002/ajoc.201800302
20. [20]
  M. Liu, K.M. Liu, D.C. Xiong, et al., Angew. Chem. Int. Ed. 59 (2020) 15204–15208. doi: 10.1002/anie.202006115
21. [21]
  M. Liu, Z.X. Luo, T. Li, et al., J. Org. Chem. 86 (2021) 16187–16194. doi: 10.1021/acs.joc.1c01318
22. [22]
  Z.X. Luo, M. Liu, T. Li, et al., Front. Chem. 9 (2021) 796690. doi: 10.3389/fchem.2021.796690
23. [23]
  H. Endo, M. Ochi, M.A. Rahman, et al., Chem. Commun. 58 (2022) 7948–7951. doi: 10.1039/D2CC02287G
24. [24]
  S. Kim, P. Nagorny, Org. Lett. 24 (2022) 2294–2298. doi: 10.1021/acs.orglett.2c00431
25. [25]
  R.Q. Wang, Q.H. Jiang, H.X. Wang, et al., Org. Lett. 25 (2023) 4252–4257. doi: 10.1021/acs.orglett.3c01185
26. [26]
  C. Qi, G. Goti, A. Sartorel, et al., Org. Lett. 26 (2024) 9328–9333. doi: 10.1021/acs.orglett.4c03511
27. [27]
  J. Wu, R. Purushothaman, F. Kallert, et al., ACS Catal. 14 (2024) 11532–11544. doi: 10.1021/acscatal.4c02322
28. [28]
  H. Endo, Y.C. Sun, N. Sasaki, et al., Chem. Commun. 61 (2025) 4483–4494. doi: 10.1039/D4CC04877F
29. [29]
  W. Priebe, G. Grynkiewicz, Formation and reactions of glycal derivatives, in: B.O. Fraser-Reid, K. Tatsuta, J. Thiem (Eds.) Glycoscience: chemistry and Chemical Biology Ⅰ–Ⅲ, Springer Berlin Heidelberg, Berlin, Heidelberg, 2001, pp. 749– 783.
30. [30]
  L. Somsák, Chem. Rev. 101 (2001) 81–136. doi: 10.1021/cr980007n
31. [31]
  C. Taillefumier, Y. Chapleur, Chem. Rev. 104 (2004) 263–292. doi: 10.1021/cr030640v
32. [32]
  T. Kaszás, M. Tóth, P. Langer, et al., Adv. Synth. Catal. 361 (2019) 105–117. doi: 10.1002/adsc.201801059
33. [33]
  Y. Yadav, R. Sagar, Chem. Asian J. 20 (2025) e202401773. doi: 10.1002/asia.202401773
34. [34]
  R. Das, M. Das, D. Mukherjee, et al., Synthesis 56 (2024) 1070–1096. doi: 10.1055/a-2223-1303
35. [35]
  C.J.M. Frédéric, S.P. Vincent, Tetrahedron 74 (2018) 6512–6519. doi: 10.1016/j.tet.2018.09.039
36. [36]
  R.R. Schmidt, Y.D. Vankar, Acc. Chem. Res. 41 (2008) 1059–1073. doi: 10.1021/ar7002495
37. [37]
  C. Palo-Nieto, A. Sau, M.C. Galan, J. Am. Chem. Soc. 139 (2017) 14041–14044. doi: 10.1021/jacs.7b08898
38. [38]
  A. Sau, R. Williams, C. Palo-Nieto, et al., Angew. Chem. Int. Ed. 56 (2017) 3640–3644. doi: 10.1002/anie.201612071
39. [39]
  C. Liu, Y. Ma, C. Pei, et al., Chin. J. Chem. 36 (2018) 1007–1010. doi: 10.1002/cjoc.201800331
40. [40]
  G. Zhao, T. Wang, Angew. Chem. Int. Ed. 57 (2018) 6120–6124. doi: 10.1002/anie.201800909
41. [41]
  Y. Dai, B. Tian, H. Chen, et al., ACS Catal. 9 (2019) 2909–2915. doi: 10.1021/acscatal.9b00336
42. [42]
  R.B. Addanki, S. Halder, P.K. Kancharla, Org. Lett. 24 (2022) 1465–1470. doi: 10.1021/acs.orglett.2c00062
43. [43]
  K.M. Liu, P.Y. Wang, Z.Y. Guo, et al., Angew. Chem. Int. Ed. 61 (2022) e202204923. doi: 10.1002/anie.202204923
44. [44]
  X.P. Gong, Y. Li, H.C. Liu, et al., CCS Chem. 5 (2023) 741–749. doi: 10.31635/ccschem.022.202201794
45. [45]
  M. Zeng, C. Yu, Y. Wang, et al., Angew. Chem. Int. Ed. 62 (2023) e202300424. doi: 10.1002/anie.202300424
46. [46]
  A. Chen, Y. Han, R. Wu, et al., Nat. Commun. 15 (2024) 5228. doi: 10.1038/s41467-024-49547-9
47. [47]
  Q. Jiao, Z. Guo, M. Zheng, et al., Adv. Sci. 11 (2024) 2308513. doi: 10.1002/advs.202308513
48. [48]
  M.Y. Lyu, S.A. Jacobo, M.K. Brown, J. Am. Chem. Soc. 146 (2024) 18866–18872. doi: 10.1021/jacs.4c06246
49. [49]
  M.K. Sharma, B. Tiwari, N. Hussain, Chem. Commun. 60 (2024) 4838–4841. doi: 10.1039/D4CC00486H
50. [50]
  Z. Shen, G. Yin, Y. Li, Chin. J. Chem. 42 (2024) 2147–2152. doi: 10.1002/cjoc.202400224
51. [51]
  Z. Shen, Y. Yu, D. Wu, et al., Nat. Commun. 15 (2024) 10167. doi: 10.1038/s41467-024-54016-4
52. [52]
  H. Shi, G. Yin, X. Lu, et al., Chin. Chem. Lett. 35 (2024) 109674. doi: 10.1016/j.cclet.2024.109674
53. [53]
  E.J. Hehre, C.F. Brewer, T. Uchiyama, et al., Biochemistry 19 (1980) 3557–3564. doi: 10.1021/bi00556a022
54. [54]
  H. Fritz, J. Lehmann, P. Schlesselmann, Carbohydr. Res. 113 (1983) 71–92. doi: 10.1016/0008-6215(83)88220-2
55. [55]
  C.F. Brewer, E.J. Hehre, J. Lehmann, et al., Liebigs Ann. Chem. 1984 (1984) 1078–1087. doi: 10.1002/jlac.198419840604
56. [56]
  A.M. Gómez, A. Pedregosa, S. Valverde, et al., Tetrahedron Lett. 44 (2003) 6111–6116. doi: 10.1016/S0040-4039(03)01455-2
57. [57]
  A.M. Gómez, A. Barrio, I. Amurrio, et al., Tetrahedron Lett. 47 (2006) 6243–6246. doi: 10.1016/j.tetlet.2006.06.133
58. [58]
  R. Peng, M.S. VanNieuwenhze, Org. Lett. 14 (2012) 1962–1965. doi: 10.1021/ol300072h
59. [59]
  C.J.M. Frédéric, J. Cornil, M. Vandamme, et al., Org. Lett. 20 (2018) 6769–6773. doi: 10.1021/acs.orglett.8b02891
60. [60]
  J. József, L. Somsák, M. Tóth, et al., Eur. J. Org. Chem. 26 (2023) e202201488. doi: 10.1002/ejoc.202201488
61. [61]
  T.V. RajanBabu, G.S. Reddy, J. Org. Chem. 51 (1986) 5458–5461. doi: 10.1021/jo00376a088
62. [62]
  H.T.T. Thien, A. Novoa, N. Pellegrini-Moïse, et al., Eur. J. Org. Chem. 2011 (2011) 6939–6951. doi: 10.1002/ejoc.201100949
63. [63]
  Y.B. Chen, S.H. Liu, M.T. Hsieh, et al., J. Org. Chem. 81 (2016) 3007–3016. doi: 10.1021/acs.joc.5b02891
64. [64]
  D. Tardieu, M. Desnoyers, C. Laye, et al., Org. Lett. 21 (2019) 7262–7267. doi: 10.1021/acs.orglett.9b02496
65. [65]
  J. Regier, S. Ghanty, Y. Bolshan, J. Org. Chem. 87 (2022) 524–530. doi: 10.1021/acs.joc.1c02533
66. [66]
  M. Lang, S. Walter, D. Hatey, et al., Org. Lett. 26 (2024) 8017–8022. doi: 10.1021/acs.orglett.4c02754
67. [67]
  G.V.M. Sharma, A.S. Chander, V. Goverdhan Reddy, et al., Tetrahedron. Lett. 41 (2000) 1997–2000. doi: 10.1016/S0040-4039(00)00083-6
68. [68]
  C.F. Chang, W.B. Yang, C.C. Chang, et al., Tetrahedron Lett. 43 (2002) 6515–6519. doi: 10.1016/S0040-4039(02)01473-9
69. [69]
  H.C. Lin, W.B. Yang, Y.F. Gu, et al., Org. Lett. 5 (2003) 1087–1089. doi: 10.1021/ol034130z
70. [70]
  H.C. Lin, C.C. Chang, J.Y. Chen, et al., Tetrahedron: Asymmetry 16 (2005) 297–301. doi: 10.1016/j.tetasy.2004.11.044
71. [71]
  H.C. Lin, Y.B. Chen, Z.P. Lin, et al., Tetrahedron 66 (2010) 5229–5234. doi: 10.1016/j.tet.2010.04.075
72. [72]
  H. Liu, A.G. Laporte, D. Tardieu, et al., J. Org. Chem. 87 (2022) 13178–13194. doi: 10.1021/acs.joc.2c01635
73. [73]
  X. Li, H. Ohtake, H. Takahashi, et al., Tetrahedron 57 (2001) 4283–4295. doi: 10.1016/S0040-4020(01)00319-2
74. [74]
  S. Habib, F. Larnaud, E. Pfund, et al., Org. Biomol. Chem. 12 (2014) 690–699. doi: 10.1039/C3OB41926F
75. [75]
  W.T. Huntress, G.F. Mitchell, Astrophys. J. 231 (1979) 456–467. doi: 10.1086/157207
76. [76]
  E. Vigren, M. Kamińska, M. Hamberg, et al., Phys. Chem. Chem. Phys. 10 (2008) 4014–4019. doi: 10.1039/b801566j
77. [77]
  E. Juaristi, G. Cuevas, Tetrahedron 48 (1992) 5019–5987. doi: 10.1016/S0040-4020(01)90118-8
78. [78]
  S.S. Nigudkar, A.V. Demchenko, Chem. Sci. 6 (2015) 2687–2704. doi: 10.1039/C5SC00280J
79. [79]
  I. Tvaroska, T. Bleha, Anomeric and exo-anomeric effects in carbohydrate chemistry, in: R.S. Tipson, D. Horton (Eds.), Advances in Carbohydrate Chemistry and Biochemistry, Advances in Carbohydrate Chemistry and Biochemistry, 47, Academic Press, 1989, pp. 45–123.
80. [80]
  G.J. Boons, Mono-and oligosaccharides: structure, con-figuration and conformation, in: G.J. Boons (Ed.), Carbohydrate Chemistry, Sheffield Academic Press, 1998, pp. 1–25.
1. [1]
  Ao Sun , Zipeng Li , Shuchun Li , Xiangbao Meng , Zhongtang Li , Zhongjun Li . Stereoselective synthesis of α-3-deoxy-D-manno-oct-2-ulosonic acid (α-Kdo) derivatives using a C3-p-tolylthio-substituted Kdo fluoride donor. Chinese Chemical Letters, 2025, 36(3): 109972-. doi: 10.1016/j.cclet.2024.109972
2. [2]
  Yidian Mo , Ao Sun , Hang Dong , Zhongtang Li , Zhongjun Li . Synthesis of α-d-fructofuranosides and difructose dianhydride Ⅳ using glycosyl fluorides as donors. Chinese Chemical Letters, 2026, 37(7): 111922-. doi: 10.1016/j.cclet.2025.111922
3. [3]
  Chen Li , Ziyuan Zhao , Shouyun Yu . Photoredox-catalyzed C-glycosylation of peptides with glycosyl bromides. Chinese Chemical Letters, 2024, 35(6): 109128-. doi: 10.1016/j.cclet.2023.109128
4. [4]
  Hongjin Shi , Guoyin Yin , Xi Lu , Yangyang Li . Stereoselective synthesis of 2-deoxy-α-C-glycosides from glycals. Chinese Chemical Letters, 2024, 35(12): 109674-. doi: 10.1016/j.cclet.2024.109674
5. [5]
  Shaojie Ding , Henan Wang , Xiaojing Dai , Yuru Lv , Xinxin Niu , Ruilian Yin , Fangfang Wu , Wenhui Shi , Wenxian Liu , Xiehong Cao . Mn-modulated Co–N–C oxygen electrocatalysts for robust and temperature-adaptative zinc-air batteries. Chinese Journal of Structural Chemistry, 2024, 43(7): 100302-100302. doi: 10.1016/j.cjsc.2024.100302
6. [6]
  Shanru Feng , Ling Wen , Li Zhang , Qinyu Jiang , Bozhao Zhang , Guohao Wu , Yue Wu , Jiabin Chen , Youcai Han , Chuhao Liu , Yu-Wu Zhong , Jiannian Yao . Magnetic field controlled electrocatalysis from a multidimensional catalytic perspective: Mechanisms, applications, and prospects for energy conversion. Chinese Journal of Structural Chemistry, 2025, 44(11): 100662-100662. doi: 10.1016/j.cjsc.2025.100662
7. [7]
  Xiang Ao , Fucheng Wu , Lin Yu , Kai Zhao , Muhammad Humayun , Chundong Wang . Tailoring antiperovskite carbide for electrocatalysis hydrogen evolution applications. Chinese Journal of Structural Chemistry, 2026, 45(4): 100851-100851. doi: 10.1016/j.cjsc.2025.100851
8. [8]
  Chunru Liu , Ligang Feng . Advances in anode catalysts of methanol-assisted water-splitting reactions for hydrogen generation. Chinese Journal of Structural Chemistry, 2023, 42(10): 100136-100136. doi: 10.1016/j.cjsc.2023.100136
9. [9]
  Guan-Nan Xing , Di-Ye Wei , Hua Zhang , Zhong-Qun Tian , Jian-Feng Li . Pd-based nanocatalysts for oxygen reduction reaction: Preparation, performance, and in-situ characterization. Chinese Journal of Structural Chemistry, 2023, 42(11): 100021-100021. doi: 10.1016/j.cjsc.2023.100021
10. [10]
  Sumiya Akter Dristy , Md Ahasan Habib , Mehedi Hasan Joni , Md Najibullah , Rutuja Mandavkar , Shusen Lin , Jihoon Lee . Binder-free bimetallic vanadium-nickel-boride-phosphide spherical structure for highly efficient and stable industrial-level water splitting. Chinese Journal of Structural Chemistry, 2025, 44(12): 100747-100747. doi: 10.1016/j.cjsc.2025.100747
11. [11]
  Pingfan Zhang , Shihuan Hong , Ning Song , Zhonghui Han , Fei Ge , Gang Dai , Hongjun Dong , Chunmei Li . Alloy as advanced catalysts for electrocatalysis: From materials design to applications. Chinese Chemical Letters, 2024, 35(6): 109073-. doi: 10.1016/j.cclet.2023.109073
12. [12]
  Ming Yue , Yi-Rong Wang , Jia-Yong Weng , Jia-Li Zhang , Da-Yu Chi , Mingjin Shi , Xiao-Gang Hu , Yifa Chen , Shun-Li Li , Ya-Qian Lan . Multi-metal porous crystalline materials for electrocatalysis applications. Chinese Chemical Letters, 2025, 36(6): 110049-. doi: 10.1016/j.cclet.2024.110049
13. [13]
  Mingying Chen , Junjie Ma , Xiyong Chen , Qian Liu , Yanhong Feng , Xijun Liu . Support engineering of single-atom electrocatalysis: Mechanism analysis and application expansion. Chinese Chemical Letters, 2026, 37(4): 111637-. doi: 10.1016/j.cclet.2025.111637
14. [14]
  Anni Wu , Chengyi Hong , Hu Zheng , Wei Teng . Multi-site synergistic relay electrocatalysis with high-entropy nanoalloys for effective nitrate reduction to ammonia. Chinese Chemical Letters, 2025, 36(12): 111066-. doi: 10.1016/j.cclet.2025.111066
15. [15]
  Sheng Qian , Jingying Wei , Junhua Wang , Yi Zhang , Huaiguo Xue , Tengfei Jiang , Jingqi Tian . Conjugated N-heterocycles in heterostructured support manipulate d-band center for hydrogen electrocatalysis. Chinese Chemical Letters, 2026, 37(8): 112106-. doi: 10.1016/j.cclet.2025.112106
16. [16]
  Mingrun Li , Bin Han , Lei Gong , Yucheng Jin , Mingyue Wang , Xu Ding , Dongdong Qi , Jianzhuang Jiang . 1D COFs with phthalocyanine functional building blocks and imide linkage for superior electrocatalytic nitrate reduction. Chinese Chemical Letters, 2026, 37(2): 110590-. doi: 10.1016/j.cclet.2024.110590
17. [17]
  Shengkai Li , Yuqin Zou , Chen Chen , Shuangyin Wang , Zhao-Qing Liu . Defect engineered electrocatalysts for C–N coupling reactions toward urea synthesis. Chinese Chemical Letters, 2024, 35(8): 109147-. doi: 10.1016/j.cclet.2023.109147
18. [18]
  Yue Zhang , Xiaoya Fan , Xun He , Tingyu Yan , Yongchao Yao , Dongdong Zheng , Jingxiang Zhao , Qinghai Cai , Qian Liu , Luming Li , Wei Chu , Shengjun Sun , Xuping Sun . Ambient electrosynthesis of urea from carbon dioxide and nitrate over Mo₂C nanosheet. Chinese Chemical Letters, 2024, 35(8): 109806-. doi: 10.1016/j.cclet.2024.109806
19. [19]
  Yahui Li , Quanchen Feng , Krisztina László , Ying Wang . High-throughput screening of high C/N-ratio homonuclear dual-atom catalysts for electrochemical reduction of nitrate to ammonia. Chinese Chemical Letters, 2026, 37(3): 111536-. doi: 10.1016/j.cclet.2025.111536
20. [20]
  Lin Zhang , Jianlong Li , Maoyuan Hu , Yao Xu , Xiaoli Xiong , Zhaoyu Jin . MOF-derived beaded stream-like nitrogen and phosphorus-codoped carbon-coated Fe₃O₄ nanocomposites via lattice-oxygen-mediated mechanism for efficient water oxidation. Chinese Chemical Letters, 2025, 36(8): 111123-. doi: 10.1016/j.cclet.2025.111123

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(11)
HTML views(0)

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