English

• Nucleic acids, proteins, and polysaccharides constitute the three fundamental classes of biomolecules essential for life. Among these, polysaccharides play critical roles in numerous biological processes, including bacterial and viral infections, cell recognition, immune regulation, inflammatory responses, and cancer metabolism [1–3]. Advances in understanding carbohydrate-receptor interactions have spurred significant progress in the synthesis of carbohydrate analogs and mimetics [4–7]. Nonetheless, significant challenges remain in glycoscience, particularly in achieving the efficient and stereoselective synthesis of bioactive oligosaccharides and glycoconjugates. Addressing these challenges requires the development of innovative synthetic platforms capable of generating diverse carbohydrate-based structures, thereby bridging the gap between fundamental glycoscience and its medical applications.

  In recent years, electrochemical organic synthesis has emerged as a powerful tool for green synthesis, offering advantages such as high atom economy, mild reaction conditions, and scalability [8–17]. These attributes make electrochemical methods particularly attractive for glycosylation reactions [18–28].

  Glycals represent an important class of polyhydroxylated chiral synthons that serve as versatile synthetic intermediates in the synthesis of oligosaccharides, glycoconjugates, and bioactive natural products [29–34]. They are broadly classified into two categories: Endo-glycals, which contain an endocyclic carbon-carbon double bond, and exo-glycals (or 1-methylene sugars), featuring an exocyclic double bond (Fig. 1a) [35]. Endo-glycals have been extensively explored and widely employed in O- and C-glycosylation reactions [20,21,26,34,36–52]. In medicinal chemistry, exo-glycals are valued as glycosidase inhibitors [53–55] and have been used in the synthesis of C-glycoside analogs via various strategies, including hydroboration/Suzuki cross-coupling [56], Stille cross-coupling [57], Heck reactions [58], radical addition [59], epoxidation [60], and others methods [56–66].

  Figure 1

  

  Figure 1.  Structural comparison of endo- and exo-glycals and their applications in O-glycosylation.

  DownLoad: Full-Size Img PowerPoint

  In contrast, O-glycosylation reactions employing exo-glycals as glycosyl donors remain underdeveloped [67–73]. Existing approaches are largely limited to two conventional pathways: (a) Lewis acid-catalyzed direct O-glycosylation [72,73] and (b) Lewis acid-promoted rearrangement reactions [69,70], both of which have been applied to synthesize biologically relevant 1′-C-methyl-O-glycosides. These methods, however, suffer from several drawbacks, including narrow substrate scope, limited stereocontrol, and harsh reaction conditions. Thus, the development of efficient and stereoselective strategies for synthesizing 1′-C-methyl-O-glycoside analogs is highly desirable.

  Our group recently reported an electrochemical method for glycosylation using endo-glycal, which afforded products in high yields with excellent selectivity, offering an efficient and novel strategy for O-glycosylation (Fig. 1d) [20]. Inspired by the structural similarities between the double bonds in exo- and endo-glycals, and encouraged by the efficiency and sustainability of electrochemical synthesis, we sought to extend this electro-promoted approach to achieve efficient and stereoselective O-glycosylation of exo-glycals (1-methylene sugars) to form 1′-C-methyl-O-glycosides (Fig. 1e). Herein, we present an electrochemical method for the efficient synthesis of O-glycoside analogs from exo-glycals and nucleophilic acceptors. The electrochemical method exhibits a combination of broad substrate scope, outstanding functional group tolerance (especially for alkenes), excellent stereocontrol, and enhanced reaction efficiency. In addition, this strategy not only expands the synthetic utility of exo-glycals but also aligns with green chemistry principles by reducing environmental impact.

  We initiated our investigation by examining the electrochemical glycosylation of benzyl protected-1-methylenesugars 1a and 2a in an undivided electrochemical cell (Table 1). Under initial conditions using Bu₄NOTf as the electrolyte, a graphite anode, a platinum plate cathode, CH₃CN as the solvent, room temperature, and a constant current of 2 mA, the target product 3a was achieved with 44% yield and exclusive α-selectivity (entry 1). Solvent screening revealed a significant influence on the reaction outcome (entries 2–4). Low or negligible yields were observed with 1,2-dimethoxyethane (DME), diethyl ether, or 1,4-dioxane. Subsequent evaluation of electrolytes, including Bu₄NBF₄, Bu₄NOAc, Bu₄NBr, KOTf and NaOTf, identified KOTf and NaOTf as superior, affording 3a in 51% and 50% yields, respectively (entries 5–9). Based on these results, KOTf (2.0 equiv.) was selected for further optimization. We then evaluated alternative electrode configurations. Employing graphite for both electrodes resulted in a diminished yield of 31% (entry 10), while a Pt/Pt setup completely inhibited the reaction (entry 11). Notably, reversing the electrodes to a Pt anode and graphite cathode significantly improved the yield to 87% (entry 12). Varying the current intensity did not lead to further enhancement (entries 13 and 14). Control experiments confirmed that both electricity and electrolyte are essential, as no reaction occurred in their absence (entries 15 and 16).

  Table 1

  

  Table 1.  Optimization of electrochemical glycosylation reaction conditions.^a

  DownLoad: CSV

  Entry	Conditions	Yield (%)a
  1	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), CH3CN	44
  2	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), DME	0
  3	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), Et2O	0
  4	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), 1,4-dioxane	< 10
  5	C(+)||Pt(-) = 2.0 mA, Bu4NBF4 (2.0 equiv.), CH3CN	< 5
  6	C(+)||Pt(-) = 2.0 mA, Bu4NOAc (2.0 equiv.), CH3CN	< 5
  7	C(+)||Pt(-) = 2.0 mA, Bu4NBr (2.0 equiv.), CH3CN	< 5
  8	C(+)||Pt(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	51
  9	C(+)||Pt(-) = 2.0 mA, NaOTf (2.0 equiv.), CH3CN	50
  10	C(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	31
  11	Pt(+)||Pt(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	0
  12	Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	87
  13	Pt(+)||C(-) = 1.0 mA, KOTf (2.0 equiv.), CH3CN	85
  14	Pt(+)||C(-) = 0.5 mA, KOTf (2.0 equiv.), CH3CN	86
  15	Pt(+)||C(-) = 2.0 mA, no electrolyte, CH3CN	0
  16	No current, KOTf (2.0 equiv.), CH3CN	0
  a Reaction conditions: undivided cell, 1a (0.1 mmol, 2.0 equiv.), 2a (0.05 mmol, 1.0 equiv.), solvent (3.0 mL), 0.5 h, r.t.

  Having established the optimal electrochemical conditions, we next evaluated the scope of glycosyl donors (Table 2). Firstly, we synthesized a series of exo-glycals, including gluco– (1a and 1g), galacto- (1b), manno- (1c), rhamno-(1d), fuco- (1e) and lacto- (1f), following established literature procedures [35,63,74]. Under the standard conditions, the reaction between 1-methylidene-2,3,4,5-tetra-O-benzyl-d-glucopyranoside (1a) and acceptor 2a afforded disaccharide 3a in 87% yield (entry 1). Notably, a variety of perbenzylated 1-methylene sugars (1b-1e) acted as competent donors, yielding the corresponding disaccharides 3b-3e in excellent yields ranging from 90% to 97% (entries 2–5). Trisaccharide 3f was also obtained in good yield when lacto-derived donor 1f was employed (entry 6). Furthermore, the 1-ethylsugar was found to be compatible with the system, furnishing glycoside 3g in 75% yield (entry 7).

  Table 2

  

  Table 2.  Scope of exo-glycal donors in the O-glycosylation reaction.^a

  DownLoad: CSV

  Entry	Donor	Acceptor	Product (yield)
  1		2a
  2		2a
  3		2a
  4		2a
  5		2a
  6		2a
  7		2a
  a Reaction conditions: Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN (3.0 mL), undivided cell, 0.5 h, r.t.

  We then explored the acceptor scope of the transformation (Table 3). Both primary and secondary non-sugar alcohols were suitable reaction partners under the standard conditions, delivering glycosides 4a-4d in 71%−95% yields. Among these, product 4d was obtained with an α/β selectivity of 22/1 (entry 4), while the others were exclusively α-configuration. Notably, the reaction could be scaled up to furnish 4b in 86% yield (739 mg, entry 2). Reactions of cyclododecanol with either exo-glucal or exo-galcal donors provided 4c and 4d in 71% and 73% yields, respectively (entries 3 and 4). Acceptors containing a free C-6 hydroxyl group underwent smooth glycosylation to afford disaccharides 4e-4f in 83%–91% yields (entries 5 and 6). Reactions with acceptors containing free C-3 or C-2 hydroxyl groups were less effective at room temperature; however, reducing the temperature to −30 ℃ improved the yields of products 4g and 4h to moderate to good levels (entries 7 and 8). Di-glycosylation of 1,1-bis(hydroxymethyl)cyclopropane and 1,12-dodecanediol with exo-glucal afforded 4i and 4j in 87% and 77% yields, respectively (entries 9 and 10).

  Table 3

  

  Table 3.  Scope of acceptors in the electrochemical O-glycosylation.^a

  DownLoad: CSV

  Entry	Donor	Acceptor	Product (yield)
  1	1a
  2	1a
  3	1a
  4	1b
  5	1a
  6	1b
  7	1a
  8	1a
  9	1a
  10	1a
  a Reaction conditions: Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN (3.0 mL), undivided cell, 0.5–1 h, r.t. b 1a (1.85 mmol, 1.5 equiv.), 1b (1.24 mmol, 1.0 equiv.), 1 h. c -30 ℃, 2 h.

  To further demonstrate the practical utility of this method, we applied the electro-glycosylation reaction to the late-stage glycosylation of natural products (Table 4). Epiandrosterone was successfully coupled with exo-glucal donor under standard reaction conditions to afford 5a in 61% yiled. Similarly, podophyllotoxin was glycosylated to give 5b in 60% yield. Beta-sitosterol was also modified using different glycosyl donors (1a and 1b), yielding products 5c and 5d in 84% and 85% yields, respectively. Cholesterol proved to be a suitable substrate as well, providing glycosides 5e and 5f in good yields.

  Table 4

  

  Table 4.  Late-stage glycosylation of natural products and pharmaceuticals.^a

  DownLoad: CSV

  Entry	Donor	Acceptor	Product (yield)
  1	1a
  2	1a
  3	1a
  4	1b
  5	1a
  6	1b
  a Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN: CH2Cl2 = 1:1 (4.0 mL), undivided cell, 1 h, r.t.

  To gain further insight into the reaction mechanism, a series of mechanistic experiments were conducted (Scheme 1). First, control experiments confirmed the essential role of electrical current and electrolyte, as no glycosylation occurred in their absence (Schemes 1a and b). Subsequently, the introduction of the radical scavenger TEMPO under standard conditions completely suppressed the formation of product 3a. Notably, intermediates 6 and 7 were detected via ESI-MS, suggesting the involvement of radical species and a radical-inhibited pathway (Scheme 1c).

  Scheme 1

  

  Scheme 1.  Control experiments and isotopic labeling.

  DownLoad: Full-Size Img PowerPoint

  Deuterium labeling experiments provided additional insight into the source of the methyl hydrogen in the product. When the reaction between 1a and 2a was performed in CD₃CN, no deuterium incorporation was observed in the product, ruling out the solvent as the hydrogen source (Scheme 1d). In a complementary experiment, reaction of 1a with CD₃OD in CH₃CN afforded deuterated product 8, confirming that the methyl proton originates from the nucleophilic acceptor (Scheme 1e).

  Based on these experimental results, along with supporting evidence from cyclic voltammetry (Figs. S7-S9 in Supporting information) and previous literature reports [73,75–80], a plausible reaction mechanism is proposed (Fig. 2). Initially, the glycosyl donor 1 is oxidized at the anode to form a radical cation intermediate Ⅰ. Concurrently, the alcohol nucleophile is reduced at the cathode, generating a hydrogen radical and an alkoxide ion. The hydrogen radical combines with intermediate Ⅰ to form carbocation intermediate Ⅱ. The approach of acetonitrile is directed by the anomeric effect preferentially from the α-face, leading to the selective formation of intermediate Ⅲ. In acetonitrile solvent, Ⅲ predominates due to effective stabilization. Significant steric hindrance from the C1-methyl group prevents nucleophilic approach from the β-face, while favoring minor dissociation back to intermediate Ⅱ. Ultimately, the alkoxide attacks intermediate Ⅲ from the sterically accessible α-face, resulting in the thermodynamically favored α-glycoside product.

  Figure 2

  

  Figure 2.  Proposed mechanism for the electrochemical O-glycosylation.

  DownLoad: Full-Size Img PowerPoint

  In concluding, we have developed an electrochemical glycosylation method for the stereoselective synthesis of O-glycosides using exo-glucals and various nucleophilic acceptors. This approach operates under simple conditions in an undivided cell, employing KOTf as the electrolyte to afford the corresponding glycosylation products in high yields with excellent selectivity. The reaction accommodates a broad range of glycosyl and non-glycosyl acceptors, consistently yielding products with exclusive α-selectivity. Scalability was demonstrated through gram-scale synthesis without compromising yield or stereoselectivity. Furthermore, the method proved effective for the late-stage glycosylation of natural products and pharmaceuticals, highlighting its potential for the discovery of carbohydrate-based drugs. This electrochemical strategy thus represents an efficient and attractive platform for synthesizing O-glycosides.

  CRediT authorship contribution statement

  Jing Zhang: Writing – original draft, Investigation. Chen-Fei Gao: Investigation. Xin-Shan Ye: Resources. De-Cai Xiong: Writing – review & editing, Writing – original draft, Supervision, Conceptualization.

  Declaration of competing interest

  The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

  Acknowledgments

  This work was supported by grants from the National Natural Science Foundation of China (Nos. 22177003, 22377003) and the Fundamental Research Funds for Central Universities.

  Supplementary materials

  Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2025.112200.

  
  
• 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.

• 

  Figure 1  Structural comparison of endo- and exo-glycals and their applications in O-glycosylation.

  下载: 全尺寸图片 幻灯片
  

  Scheme 1  Control experiments and isotopic labeling.

  下载: 全尺寸图片 幻灯片
  

  Figure 2  Proposed mechanism for the electrochemical O-glycosylation.

  下载: 全尺寸图片 幻灯片

  Table 1.  Optimization of electrochemical glycosylation reaction conditions.^a

  Entry	Conditions	Yield (%)a
  1	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), CH3CN	44
  2	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), DME	0
  3	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), Et2O	0
  4	C(+)||Pt(-) = 2.0 mA, Bu4NOTf (2.0 equiv.), 1,4-dioxane	< 10
  5	C(+)||Pt(-) = 2.0 mA, Bu4NBF4 (2.0 equiv.), CH3CN	< 5
  6	C(+)||Pt(-) = 2.0 mA, Bu4NOAc (2.0 equiv.), CH3CN	< 5
  7	C(+)||Pt(-) = 2.0 mA, Bu4NBr (2.0 equiv.), CH3CN	< 5
  8	C(+)||Pt(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	51
  9	C(+)||Pt(-) = 2.0 mA, NaOTf (2.0 equiv.), CH3CN	50
  10	C(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	31
  11	Pt(+)||Pt(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	0
  12	Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN	87
  13	Pt(+)||C(-) = 1.0 mA, KOTf (2.0 equiv.), CH3CN	85
  14	Pt(+)||C(-) = 0.5 mA, KOTf (2.0 equiv.), CH3CN	86
  15	Pt(+)||C(-) = 2.0 mA, no electrolyte, CH3CN	0
  16	No current, KOTf (2.0 equiv.), CH3CN	0
  a Reaction conditions: undivided cell, 1a (0.1 mmol, 2.0 equiv.), 2a (0.05 mmol, 1.0 equiv.), solvent (3.0 mL), 0.5 h, r.t.

  下载: 导出CSV

  Table 2.  Scope of exo-glycal donors in the O-glycosylation reaction.^a

  Entry	Donor	Acceptor	Product (yield)
  1		2a
  2		2a
  3		2a
  4		2a
  5		2a
  6		2a
  7		2a
  a Reaction conditions: Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN (3.0 mL), undivided cell, 0.5 h, r.t.

  下载: 导出CSV

  Table 3.  Scope of acceptors in the electrochemical O-glycosylation.^a

  Entry	Donor	Acceptor	Product (yield)
  1	1a
  2	1a
  3	1a
  4	1b
  5	1a
  6	1b
  7	1a
  8	1a
  9	1a
  10	1a
  a Reaction conditions: Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN (3.0 mL), undivided cell, 0.5–1 h, r.t. b 1a (1.85 mmol, 1.5 equiv.), 1b (1.24 mmol, 1.0 equiv.), 1 h. c -30 ℃, 2 h.

  下载: 导出CSV

  Table 4.  Late-stage glycosylation of natural products and pharmaceuticals.^a

  Entry	Donor	Acceptor	Product (yield)
  1	1a
  2	1a
  3	1a
  4	1b
  5	1a
  6	1b
  a Pt(+)||C(-) = 2.0 mA, KOTf (2.0 equiv.), CH3CN: CH2Cl2 = 1:1 (4.0 mL), undivided cell, 1 h, r.t.

  下载: 导出CSV
•