Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Stereoselective and site-divergent synthesis of C-glycosides

Nature Chemistry volume 16, pages 2054–2065 (2024)Cite this article

Subjects

Abstract

Carbohydrates play important roles in medicinal chemistry and biochemistry. However, their synthesis relies on specially designed glycosyl donors, which are often unstable and require multi-step synthesis. Furthermore, the catalytic and stereoselective installation of arylated quaternary stereocentres on sugar rings remains a formidable challenge. Here we report a facile and versatile method for the synthesis of diverse C–R (where R is an aryl, heteroaryl, alkenyl, alkynyl or alkyl) glycosides from readily available and bench-stable 1-deoxyglycosides. The reaction proceeds under mild conditions and exhibits high stereoselectivity across a broad range of glycosyl units. This protocol can be used to synthesize challenging 2-deoxyglycosides, unprotected glycosides, non-classical glycosides and deuterated glycosides. We further developed the catalyst-controlled site-divergent functionalization of carbohydrates for the synthesis of various unexplored carbohydrates containing arylated quaternary stereocentres that are inaccessible by existing methods. The synthetic utility of this strategy is further demonstrated in the synthesis of pharmaceutically relevant molecules and carbohydrates.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The significance of glycosides and their synthesis strategies.
Fig. 2: Four-pronged stereoselective synthesis of C-glycosides and mechanistic investigations.
Fig. 3: Design of site-divergent editing of sugars.
Fig. 4: Mechanistic studies.
Fig. 5: Applications in the synthesis of biologically active natural products and C-glycosides.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available within the Article and its Supplementary Information files. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2262193 (14), 2292208 (23), 2251328 (60), 2235883 (72), 2292209 (79) and 2251329 (107). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

References

  1. Elshahawi, S. I., Shaaban, K. A., Kharel, M. K. & Thorson, J. S. A comprehensive review of glycosylated bacterial natural products. Chem. Soc. Rev. 44, 7591–7697 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Bokor, É. et al. C-glycopyranosyl arenes and hetarenes: synthetic methods and bioactivity focused on antidiabetic potential. Chem. Rev. 117, 1687–1764 (2017).

    CAS  PubMed  Google Scholar 

  3. Cao, X. et al. Carbohydrate-based drugs launched during 2000–2021. Acta Pharm. Sin. B 12, 3783–3821 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bera, S., Chatterjee, B. & Mondal, D. Construction of quaternary stereocenters on carbohydrate scaffolds. RSC Adv. 6, 77212–77242 (2016).

    CAS  Google Scholar 

  5. Štambaský, J., Hocek, M. & Kočovský, P. C-nucleosides: synthetic strategies and biological applications. Chem. Rev. 109, 6729–6764 (2009).

    PubMed  Google Scholar 

  6. Yang, Y. & Yu, B. Recent advances in the chemical synthesis of C-glycosides. Chem. Rev. 117, 12281–12356 (2017).

    CAS  PubMed  Google Scholar 

  7. Kitamura, K., Ando, Y., Matsumoto, T. & Suzuki, K. Total synthesis of aryl C‑glycoside natural products: strategies and tactics. Chem. Rev. 118, 1495–1598 (2018).

    CAS  PubMed  Google Scholar 

  8. Nielsen, M. M. & Pedersen, C. M. Catalytic glycosylations in oligosaccharide synthesis. Chem. Rev. 118, 8285–8358 (2018).

    CAS  PubMed  Google Scholar 

  9. McKay, M. J. & Nguyen, H. M. Recent advances in transition metal-catalyzed glycosylation. ACS Catal. 2, 1563–1595 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen, A., Yang, B., Zhou, Z. & Zhu, F. Recent advances in transition-metal-catalyzed glycosyl cross-coupling reactions. Chem Catal. 2, 3430–3470 (2022).

    CAS  Google Scholar 

  11. Xu, L., Fan, N. & Hu, X. Recent development in the synthesis of C-glycosides involving glycosyl radicals. Org. Biomol. Chem. 18, 5095–5109 (2020).

    CAS  PubMed  Google Scholar 

  12. Gong, H. & Gagné, M. R. Diastereoselective Ni-catalyzed Negishi cross-coupling approach to saturated, fully oxygenated C-Alkyl and C-Aryl glycosides. J. Am. Chem. Soc. 130, 12177–12183 (2008).

    CAS  PubMed  Google Scholar 

  13. Zhao, C., Jia, X., Wang, X. & Gong, H. Ni-catalyzed reductive coupling of alkyl acids with unactivated tertiary alkyl and glycosyl halides. J. Am. Chem. Soc. 136, 17645–17651 (2014).

    CAS  PubMed  Google Scholar 

  14. Liu, J., Lei, C. & Gong, H. Nickel-catalyzed reductive coupling of glucosyl halides with aryl/vinyl halides enabling β-selective preparation of C-aryl/vinyl glucosides. Sci. China Chem. 62, 1492–1496 (2019).

    Google Scholar 

  15. Li, Y. et al. Chemoselective and diastereoselective synthesis of C-Aryl nucleoside analogues by nickel-catalyzed cross-coupling of furanosyl acetates with aryl iodides. Angew. Chem. Int. Ed. 61, e202110391 (2022).

    CAS  Google Scholar 

  16. Wang, Q. et al. Palladium-catalysed C–H glycosylation for synthesis of C-aryl glycosides. Nat. Catal. 2, 793–800 (2019).

    CAS  Google Scholar 

  17. Sun, Q. et al. Stereoselective synthesis of C-vinyl glycosides via palladium catalyzed C–H glycosylation of alkenes. Angew. Chem. Int. Ed. 60, 19620–19625 (2021).

    CAS  Google Scholar 

  18. Lv, W., Chen, Y., Wen, S., Ba, D. & Cheng, G. Modular and stereoselective synthesis of C-aryl glycosides via Catellani reaction. J. Am. Chem. Soc. 142, 14864–14870 (2020).

    CAS  PubMed  Google Scholar 

  19. Wang, Q., Duan, J., Tang, P., Chen, G. & He, G. Synthesis of non-classical heteroaryl C-glycosides via Minisci-type alkylation of N-heteroarenes with 4-glycosyl-dihydropyridines. Sci. China Chem. 63, 1613–1618 (2020).

    CAS  Google Scholar 

  20. Ghouilem, J. et al. Diastereoselective Pd-catalyzed anomeric C(sp3)–H activation: synthesis of α-(hetero)aryl C-glycosides. ACS Catal. 11, 1818–1826 (2021).

    CAS  Google Scholar 

  21. Nicolas, L. et al. Diastereoselective metal-catalyzed synthesis of C-aryl and C-vinyl glycosides. Angew. Chem. Int. Ed. 51, 11101–11104 (2012).

    CAS  Google Scholar 

  22. Adak, L. et al. Synthesis of aryl C-glycosides via iron-catalyzed cross coupling of halosugars: stereoselective anomeric arylation of glycosyl radicals. J. Am. Chem. Soc. 139, 10693–10701 (2017).

    CAS  PubMed  Google Scholar 

  23. Wang, Q. et al. Iron-catalysed reductive cross-coupling of glycosyl radicals for the stereoselective synthesis of C-glycosides. Nat. Synth. 1, 235–244 (2022).

    Google Scholar 

  24. Zhu, F., Rourke, M. J., Yang, T., Rodriguez, J. & Walczak, M. A. Highly stereospecific cross-coupling reactions of anomeric stannanes for the synthesis of C‑aryl glycosides. J. Am. Chem. Soc. 138, 12049–12052 (2016).

    CAS  PubMed  Google Scholar 

  25. Zhu, F., Rodriguez, J., O’Neill, S. & Walczak, M. A. Acyl glycosides through stereospecific glycosyl cross-coupling: rapid access to C(sp3)-linked glycomimetics. ACS Cent. Sci. 4, 1652–1662 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ma, Y. et al. Highly stereoselective synthesis of aryl/heteroaryl-C-nucleosides via the merger of photoredox and nickel catalysis. Chem. Commun. 55, 14657–14660 (2019).

    CAS  Google Scholar 

  27. Zhu, M. & Messaoudi, S. Diastereoselective decarboxylative alkynylation of anomeric carboxylic acids using Cu/photoredox dual catalysis. ACS Catal. 11, 6334–6342 (2021).

    CAS  Google Scholar 

  28. Ji, P. et al. Visible-light-mediated, chemo- and stereoselective radical process for the synthesis of C-glycoamino acids. Org. Lett. 21, 3086–3092 (2019).

    CAS  PubMed  Google Scholar 

  29. Qi, R. et al. Visible-light-promoted stereoselective C(sp3)–H glycosylation for the synthesis of C-glycoamino acids and C-glycopeptides. Angew. Chem. Int. Ed. 61, e202200822 (2022).

    CAS  Google Scholar 

  30. Miquel, N., Doisneau, G. & Beau, J. M. Reductive samariation of anomeric 2-pyridylsulfones with catalytic nickel: an unexpected improvement in the synthesis of 1,2-trans-diequatorial C-glycosyl compounds. Angew. Chem. Int. Ed. 39, 4111–4114 (2000).

    CAS  Google Scholar 

  31. Mazkas, D., Skrydstrup, T., Doumeix, O. & Beau, J. M. Samarium iodide induced intramolecular C-glycoside formation: efficient radical formation in the absence of an additive. Angew. Chem. Int. Ed. 33, 1383–1386 (1994).

    Google Scholar 

  32. Shang, W. et al. Generation of glycosyl radicals from glycosyl sulfoxides and its use in the synthesis of C‐linked glycoconjugates. Angew. Chem. Int. Ed. 60, 385–390 (2021).

    CAS  Google Scholar 

  33. Wang, Q. et al. Visible light activation enables desulfonylative cross-coupling of glycosyl sulfones. Nat. Synth. 1, 967–974 (2022).

    Google Scholar 

  34. Xie, D., Wang, Y., Zhang, X., Fu, Z. & Niu, D. Alkyl/glycosyl sulfoxides as radical precursors and their use in the synthesis of pyridine derivatives. Angew. Chem. Int. Ed. 61, e202204922 (2022).

    CAS  Google Scholar 

  35. Zhang, C. et al. Direct synthesis of unprotected aryl C-glycosides by photoredox Ni-catalysed cross-coupling. Nat. Synth. 2, 251–260 (2023).

    Google Scholar 

  36. Masuda, K., Nagatomo, M. & Inoue, M. Direct assembly of multiply oxygenated carbon chains by decarbonylative radical-radical coupling reactions. Nat. Chem. 9, 207–212 (2017).

    CAS  PubMed  Google Scholar 

  37. Wei, Y., Ben-ȥvi, B. & Diao, T. Diastereoselective synthesis of aryl C-glycosides from glycosyl esters via C–O bond homolysis. Angew. Chem. Int. Ed. 60, 9433–9438 (2021).

    CAS  Google Scholar 

  38. Jiang, Y. et al. Catalytic multicomponent synthesis of C-acyl glycosides by consecutive cross-electrophile couplings. Angew. Chem. Int. Ed. 61, e202211043 (2022).

    CAS  Google Scholar 

  39. Wei, Y., Wang, Q. & Koh, M. J. A photoinduced, nickel-catalyzed reaction for the stereoselective assembly of C-linked glycosides and glycopeptides. Angew. Chem. Int. Ed. 61, e202214247 (2022).

    Google Scholar 

  40. Chen, A. et al. Recent advances in glycosylation involving novel anomeric radical precursors. J. Carbohydr. Chem. 40, 361–400 (2021).

    CAS  Google Scholar 

  41. Shatskiy, A., Stepanova, E. V. & Kärkäs, M. D. Exploiting photoredox catalysis for carbohydrate modification through C–H and C–C bond activation. Nat. Rev. Chem. 6, 782–805 (2022).

    CAS  PubMed  Google Scholar 

  42. Ghouilem, J., de Robichon, M., Le Bideau, F., Ferry, A. & Messaoudi, S. Emerging organometallic methods for the synthesis of C-branched (hetero)aryl, alkenyl, and alkyl glycosides: C–H functionalization and dual photoredox approaches. Chemistry 27, 491–511 (2021).

    CAS  PubMed  Google Scholar 

  43. Probst, N. et al. Palladium(II)-catalyzed diastereoselective 2,3-trans C(sp3)–H arylation of glycosides. ACS Catal. 8, 7781–7786 (2018).

    CAS  Google Scholar 

  44. Wu, J., Kopp, A. & Ackermann, L. Synthesis of C-oligosaccharides through versatile C(sp3)–H glycosylation of glycosides. Angew. Chem. Int. Ed. 61, e202114993 (2022).

    CAS  Google Scholar 

  45. Dumoulin, A., Matsui, J. K., Gutiérrez-Bonet, Á. & Molander, G. A. Synthesis of non-classical arylated C-saccharides through nickel/photoredox dual catalysis. Angew. Chem. Int. Ed. 57, 6614–6618 (2018).

    CAS  Google Scholar 

  46. Zhao, G. et al. Nickel-catalyzed radical migratory coupling enables C‑2 arylation of carbohydrates. J. Am. Chem. Soc. 143, 8590–8596 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Cao, H., Tang, X., Tang, H., Yuan, Y. & Wu, J. Photoinduced intermolecular hydrogen atom transfer reactions in organic synthesis. Chem Catal. 1, 523–598 (2021).

    CAS  Google Scholar 

  48. Capaldo, L., Ravelli, D. & Fagnoni, M. Direct photocatalyzed hydrogen atom transfer (HAT) for aliphatic C–H bonds elaboration. Chem. Rev. 122, 1875–1924 (2022).

    CAS  PubMed  Google Scholar 

  49. Heitz, D. R., Tellis, J. C. & Molander, G. A. Photochemical nickel-catalyzed C–H arylation: synthetic scope and mechanistic investigations. J. Am. Chem. Soc. 138, 12715–12718 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Shaw, M. H., Shurtleff, V. W., Terrett, J. A., Cuthbertson, J. D. & MacMillan, D. W. C. Native functionality in triple catalytic cross-coupling: sp3 C–H bonds as latent nucleophiles. Science 352, 1304–1308 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Shields, B. J. & Doyle, A. G. Direct C(sp3)–H cross coupling enabled by catalytic generation of chlorine radicals. J. Am. Chem. Soc. 138, 12719–12722 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Shen, Y., Gu, Y. & Martin, R. sp3 C–H arylation and alkylation enabled by the synergy of triplet excited ketones and nickel catalysts. J. Am. Chem. Soc. 140, 12200–12209 (2018).

    CAS  PubMed  Google Scholar 

  53. Twilton, J. et al. The merger of transition metal and photocatalysis. Nat. Rev. Chem. 1, 0052 (2017).

    CAS  Google Scholar 

  54. Wang, C., Dixneuf, P. H. & Soulé, J. F. Photoredox catalysis for building C–C bonds from C(sp2)–H bonds. Chem. Rev. 118, 7532–7585 (2018).

    CAS  PubMed  Google Scholar 

  55. Tellis, J. C. et al. Single-electron transmetalation via photoredox/nickel dual catalysis: unlocking a new paradigm for sp3–sp2 cross-coupling. Acc. Chem. Res. 49, 1429–1439 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Cheung, K. P. S., Sarkar, S. & Gevorgyan, V. Visible light-induced transition metal catalysis. Chem. Rev. 122, 1543–1625 (2022).

    PubMed  Google Scholar 

  57. Skubi, K. L., Blum, T. R. & Yoon, T. P. Dual catalysis strategies in photochemical synthesis. Chem. Rev. 16, 10035–10074 (2016).

    Google Scholar 

  58. Chan, A. Y. et al. Metallaphotoredox: the merger of photoredox and transition metal catalysis. Chem. Rev. 122, 1485–1542 (2022).

    CAS  PubMed  Google Scholar 

  59. Holmberg-Douglas, N. & Nicewicz, D. A. Photoredox-catalyzed C–H functionalization reactions. Chem. Rev. 122, 1925–2016 (2022).

    CAS  PubMed  Google Scholar 

  60. Jeffrey, J. L., Terrett, J. A. & MacMillan, D. W. C. O–H hydrogen bonding promotes H-atom transfer from a C–H bonds for C-alkylation of alcohols. Science 349, 1532–1536 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Dimakos, V., Su, H. Y., Garrett, G. E. & Taylor, M. S. Site-selective and stereoselective C–H alkylations of carbohydrates via combined diarylborinic acid and photoredox catalysis. J. Am. Chem. Soc. 141, 5149–5153 (2019).

    CAS  PubMed  Google Scholar 

  62. Gorelik, D. J., Turner, J. A., Virk, T. S., Foucher, D. A. & Taylor, M. S. Site- and stereoselective C–H alkylations of carbohydrates enabled by cooperative photoredox, hydrogen atom transfer, and organotin catalysis. Org. Lett. 23, 5180–5518 (2021).

    CAS  PubMed  Google Scholar 

  63. Matsumoto, A., Yamamoto, M. & Maruoka, K. Cationic DABCO-based catalyst for site-selective C–H alkylation via photoinduced hydrogen-atom transfer. ACS Catal. 12, 2045–2051 (2022).

    CAS  Google Scholar 

  64. Wan, L. C., Witte, M. D. & Minnaard, A. J. Site-selective carbon–carbon bond formation in unprotected monosaccharides using photoredox catalysis. Chem. Commun. 53, 4926–4929 (2017).

    CAS  Google Scholar 

  65. Chen, D., Chu, J. C. K. & Rovis, T. Directed γ-C(sp3)–H alkylation of carboxylic acid derivatives through visible light photoredox catalysis. J. Am. Chem. Soc. 139, 14897–14900 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Li, Y., Miyamoto, S., Torigoe, T. & Kuninobu, Y. Regioselective C(sp3)–H alkylation of a fructopyranose derivative by 1,6-HAT. Org. Biomol. Chem. 19, 3124–3127 (2021).

    CAS  PubMed  Google Scholar 

  67. Jeffery, A. & Nair, V. An improved method for the synthesis of anhydroalditols. Tetrahedron Lett. 36, 3627–3630 (1995).

    CAS  Google Scholar 

  68. Ye, Y., Chen, H., Yao, K. & Gong, H. Iron-catalyzed reductive vinylation of tertiary alkyl oxalates with activated vinyl halides. Org. Lett. 22, 2070–2075 (2020).

    CAS  PubMed  Google Scholar 

  69. Salamone, M. & Bietti, M. Tuning reactivity and selectivity in hydrogen atom transfer from aliphatic C–H bonds to alkoxyl radicals: role of structural and medium effects. Acc. Chem. Res. 48, 2895–2903 (2015).

    CAS  PubMed  Google Scholar 

  70. Dondi, D. et al. Regio- and stereoselectivity in the decatungstate photocatalyzed alkylation of alkenes by alkylcyclohexanes. Chemistry 15, 7949–7957 (2009).

    CAS  PubMed  Google Scholar 

  71. Perry, I. B. et al. Direct arylation of strong aliphatic C–H bonds. Nature 560, 70–75 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Ravelli, D., Fagnoni, M., Fukuyama, T., Nishikawa, T. & Ryu, I. Site-selective C–H functionalization by decatungstate anion photocatalysis: synergistic control by polar and steric effects expands the reaction scope. ACS Catal. 8, 701–713 (2018).

    CAS  Google Scholar 

  73. Ke, Y., Li, W., Liu, W. & Kong, W. Ni-catalyzed ligand-controlled divergent and selective synthesis. Sci. China Chem. 66, 2951–2976 (2023).

    CAS  Google Scholar 

  74. Chen, K. et al. Functional-group translocation of cyano groups by reversible C–H sampling. Nature 620, 1007–1012 (2023).

    CAS  PubMed  Google Scholar 

  75. Ping, Y. et al. Switchable 1,2-rearrangement enables expedient synthesis of structurally diverse fluorine-containing scaffolds. J. Am. Chem. Soc. 144, 11626–11637 (2022).

    CAS  PubMed  Google Scholar 

  76. van Rijssel, E. R. et al. Furanosyl oxocarbenium ion stability and stereoselectivity. Angew. Chem. Int. Ed. 53, 10381–10385 (2014).

    Google Scholar 

  77. Xu, G. et al. Design, synthesis, and biological evaluation of deuterated C-aryl glycoside as a potent and long-acting renal sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes. J. Med. Chem. 57, 1236–1251 (2014).

    CAS  PubMed  Google Scholar 

  78. Fernandes, R. A., Chavan, V. P., Mulay, S. V. & Manchoju, A. Chiron approach to the total synthesis of (−)-juglomycin A, (+)-kalafungin, (+)-frenolicin B, and (+)-deoxyfrenolicin. J. Org. Chem. 77, 10455–10460 (2012).

    CAS  PubMed  Google Scholar 

  79. Hrdlicka, P. J. et al. Synthesis and biological evaluation of nucleobase-modified analogs of the anticancer compounds 3′-C-ethynyluridine (EUrd) and 3′-C-ethynylcytidine (ECyd). Bioorg. Med. Chem. 13, 1249–1260 (2005).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This project was supported by the National Natural Science Foundation of China (22171215 to W.K., 22301225 to Y.P. and 22201222 to Q.X.), the Cultivation Program of Wuhan Institute of Photochemistry and Technology (GHY2023KF007 to W.K.), the National Key R&D Program of China (2022YFA1505100 and 2023YFA1508600 to Q.X.), Hubei Provincial Outstanding Youth Fund (2022CFA092 to W.K.), Hubei Provincial Natural Science Foundation (2023AFB034 to Y.P.) and GuangDong Basic and Applied Basic Research Foundation (2022A1515010246 to W.K. and 2022A1515110113 to Y.P.). We acknowledge the Core Facility of Wuhan University for X-ray single crystal diffraction analysis. X.Q. acknowledges the supercomputing system in the Supercomputing Center of Wuhan University.

Author information

Author notes

  1. These authors contributed equally: Sheng Xu, Yuanyuan Ping.

Authors and Affiliations

  1. The Institute for Advanced Studies, Wuhan University, Wuhan, China

    Sheng Xu, Yuanyuan Ping, Yang Ke, Rui Miao & Wangqing Kong

  2. State Key Laboratory of Power Grid Environmental Protection, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, China

    Minghao Xu, Guozhen Wu & Xiaotian Qi

  3. Wuhan Institute of Photochemistry and Technology, Wuhan, China

    Wangqing Kong

Authors
  1. Sheng Xu
    View author publications

    Search author on:PubMed Google Scholar

  2. Yuanyuan Ping
    View author publications

    Search author on:PubMed Google Scholar

  3. Minghao Xu
    View author publications

    Search author on:PubMed Google Scholar

  4. Guozhen Wu
    View author publications

    Search author on:PubMed Google Scholar

  5. Yang Ke
    View author publications

    Search author on:PubMed Google Scholar

  6. Rui Miao
    View author publications

    Search author on:PubMed Google Scholar

  7. Xiaotian Qi
    View author publications

    Search author on:PubMed Google Scholar

  8. Wangqing Kong
    View author publications

    Search author on:PubMed Google Scholar

Contributions

W.K. conceived and directed this project. S.X., Y.P., Y.K. and R.M. conducted the experimental investigations. M.X., G.W. and X.Q. performed the DFT calculations. S.X. and Y.P. analysed and interpreted the experimental data. W.K. and X.Q. wrote the manuscript with feedback from other authors. All authors contributed to discussions. S.X. and Y.P. contributed equally.

Corresponding authors

Correspondence to Xiaotian Qi or Wangqing Kong.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Chemistry thanks Markus Kärkäs and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Computational studies of the ligand-controlled site-selective sugar arylation with aryl bromide.

a, Free energy profile of Ni(0)-catalyzed sugar arylation with ligand DTBPy (L1). b, Free energy profile of Ni(0)-catalyzed sugar arylation with ligand TBTPy (L2). Black path denotes the reaction of 2º radical 56 and the gray path denotes the reaction of 3º radical 57. See Supplementary Fig. 51 for full free energy profile of Ni(0)/L2-catalyzed sugar arylation with 3º radical 57. All energies were calculated at M06/6-311+G(d,p)–SDD/SMD(acetonitrile)//B3LYP-D3(BJ)/6-31G(d)–LANL2DZ level of theory.

Supplementary information

Supplementary Information

Supplementary Tables 1–44, Figs. 1–131, optimization studies, experimental procedures, product characterization and X-ray crystallographic analysis.

Supplementary Data 1

Nuclear magnetic resonance spectra.

Supplementary Data 2

Crystallographic data for compound 14, CCDC reference 2262193.

Supplementary Data 3

Crystallographic data for compound 23, CCDC reference 2292208.

Supplementary Data 4

Crystallographic data for compound 60, CCDC reference 2251328.

Supplementary Data 5

Crystallographic data for compound 72, CCDC reference 2235883.

Supplementary Data 6

Crystallographic data for compound 79, CCDC reference 2292209.

Supplementary Data 7

Crystallographic data for compound 107, CCDC reference 2251329.

Supplementary Data 8

Computational details.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, S., Ping, Y., Xu, M. et al. Stereoselective and site-divergent synthesis of C-glycosides. Nat. Chem. 16, 2054–2065 (2024). https://doi.org/10.1038/s41557-024-01629-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41557-024-01629-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing