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:

Iron-catalysed reductive cross-coupling of glycosyl radicals for the stereoselective synthesis of C-glycosides

Nature Synthesis volume 1, pages 235–244 (2022)Cite this article

Subjects

Abstract

Stereochemically defined C-glycosides are prized for their biological activity. Developing a catalytic method that comprises non-precious metals to synthesize these C-glycosides remains challenging. Here, starting from readily accessible glycosyl chlorides, we show that an Earth-abundant iron-based catalyst promotes the facile generation of glycosyl radicals, which either react directly with an unsaturated electrophile or are captured by an organonickel species to facilitate C−C bond formation under mild reductive conditions. Exploration of these two reaction pathways across a range of substrates has produced a diverse array of C-glycoside products functionalized with alkenyl, alkynyl or aromatic anomeric groups, with excellent diastereocontrol. Mechanistic control and electron paramagnetic resonance spectroscopic experiments indicate that the active catalytic species is a low-valent iron complex formed through Mn reduction. The method was applied in the stereoselective synthesis of bioactive C-glycosides and therapeutically relevant analogues.

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

Access options

Buy this article

  • Purchase on Springer Link
  • 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 C-glycosides and the existing iron-catalysed protocols that generate them.
Fig. 2: Designing a reductive strategy that leverages iron catalysis to access diverse stereodefined C-glycosides.
Fig. 3: Reaction development.
Fig. 4: Mechanistic studies.
Fig. 5: Access to biologically relevant carbohydrates and analogues.

Similar content being viewed by others

Data availability

All data supporting the findings of this study are available within the Article and its Supplementary Information. Crystallographic data for the structure (6f) reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition number CCDC 2056391. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

References

  1. Han, F.-S. Transition-metal-catalyzed Suzuki–Miyaura cross-coupling reactions: a remarkable advance from palladium to nickel catalysts. Chem. Soc. Rev. 42, 5270–5298 (2013).

    Article  CAS  PubMed  Google Scholar 

  2. Biffis, A., Centomo, P., Del Zotto, A. & Zecca, M. Pd metal catalysts for cross-couplings and related reactions in the 21st century: a critical review. Chem. Rev. 118, 2249–2295 (2018).

    Article  CAS  PubMed  Google Scholar 

  3. Magano, J. & Dunetz, J. R. Large-scale applications of transition metal-catalyzed couplings for the synthesis of pharmaceuticals. Chem. Rev. 111, 2177–2250 (2011).

    Article  CAS  PubMed  Google Scholar 

  4. Nicolaou, K. C., Bulger, P. G. & Sarlah, D. Palladium-catalyzed cross-coupling reactions in total synthesis. Angew. Chem. Int. Ed. 44, 4442–4489 (2005).

    Article  CAS  Google Scholar 

  5. Corbet, J. P. & Mignani, G. Selected patented cross-coupling reaction technologies. Chem. Rev. 106, 2651–2710 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Buono, F., Nguyen, T., Qu, B., Wu, H. & Haddad, N. Recent advances in nonprecious metal catalysis. Org. Process Res. Dev. 25, 1471–1495 (2021).

    Article  CAS  Google Scholar 

  7. Fürstner, A., Leitner, A., Méndez, M. & Krause, H. Iron-catalyzed cross-coupling reactions. J. Am. Chem. Soc. 124, 13856–13863 (2002).

    Article  PubMed  Google Scholar 

  8. Campeau, L. C. & Hazari, N. Cross-coupling and related reactions: connecting past success to the development of new reactions for the future. Organometallics 38, 3–35 (2019).

    Article  CAS  PubMed  Google Scholar 

  9. Tasker, S. Z., Standley, E. A. & Jamison, T. F. Recent advances in homogeneous nickel catalysis. Nature 509, 299–309 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Holland, P. L. Reaction: opportunities for sustainable catalysts. Chem 2, 443–447 (2017).

    Article  CAS  Google Scholar 

  11. Bauer, I. & Knölker, H.-J. Iron catalysis in organic synthesis. Chem. Rev. 115, 3170–3387 (2015).

    Article  CAS  PubMed  Google Scholar 

  12. Fürstner, A. Iron catalysis in organic synthesis: a critical assessment of what it takes to make this base metal a multitasking champion. ACS Cent. Sci. 2, 778–789 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Rana, S., Biswas, J. P., Paul, S., Paik, A. & Maiti, D. Organic synthesis with the most abundant transition metal—iron: from rust to multitasking catalysts. Chem. Soc. Rev. 50, 243–472 (2021).

    Article  CAS  PubMed  Google Scholar 

  14. Piontek, A., Bisz, E. & Szostak, M. Iron-catalyzed cross-couplings in the synthesis of pharmaceuticals: in pursuit of sustainability. Angew. Chem. Int. Ed. 57, 11116–11128 (2018).

    Article  CAS  Google Scholar 

  15. Mako, T. L. & Byers, J. A. Recent advances in iron-catalysed cross coupling reactions and their mechanistic underpinning. Inorg. Chem. Front. 3, 766–790 (2016).

    Article  CAS  Google Scholar 

  16. Zweig, J. E., Kim, D. E. & Newhouse, T. R. Methods utilizing first-row transition metals in natural product total synthesis. Chem. Rev. 117, 11680–11752 (2017).

    Article  CAS  PubMed  Google Scholar 

  17. Neidig, M. L. et al. Development and evolution of mechanistic understanding in iron-catalyzed cross-coupling. Acc. Chem. Res. 52, 140–150 (2019).

    Article  CAS  PubMed  Google Scholar 

  18. Sears, J. D., Neate, P. G. N. & Neidig, M. L. Intermediates and mechanism in iron-catalyzed cross-coupling. J. Am. Chem. Soc. 140, 11872–11883 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  20. Everson, D. A. & Weix, D. J. Cross-electrophile coupling: principles of reactivity and selectivity. J. Org. Chem. 79, 4793–4798 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Beau, J.-M. & Gallagher, T. in Glycoscience Synthesis of Substrate Analogs and Mimetics (eds Driguez, H. & Thiem, J.) 1−54 (Springer, 1998).

  22. Nicotra, F. Synthesis of C-glycosides of biological interest. Top. Curr. Chem. 187, 55–83 (1997).

    Article  CAS  Google Scholar 

  23. Yuan, X. J. & Linhardt, R. J. Recent advances in stereoselective C-glycoside synthesis. Tetrahedron 54, 9912–9959 (1998).

    Google Scholar 

  24. Postema, M. H. D. Recent developments in the synthesis of C-glycosides. Tetrahedron 48, 8545–8599 (1992).

    Article  CAS  Google Scholar 

  25. 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).

    Article  CAS  PubMed  Google Scholar 

  26. Lo, J.-C., Gui, J., Yabe, Y., Pan, C. M. & Baran, P. S. Functionalized olefin cross-coupling to construct carbon–carbon bonds. Nature 516, 343–348 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tardieu, D. et al. Stereoselective synthesis of C,C-glycosides from exo-glycals enabled by iron-mediated hydrogen atom transfer. Org. Lett. 18, 7262–7267 (2019).

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  29. Granier, T. & Vasella, A. Synthesis and evaluation as glycosidase inhibitors of 1H-imidazol-2-yl C-glycopyranosides. Helv. Chim. Acta 78, 1738–1746 (1995).

    Article  CAS  Google Scholar 

  30. Temburnikar, K. & Seley-Radtke, K. L. Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides. Beilstein J. Org. Chem. 14, 772–785 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. Guisán-Ceinos, M., Tato, F., Buñuel, E., Calle, P. & Cárdenas, D. J. Fe-catalysed Kumada-type alkyl–alkyl cross-coupling. Evidence for the intermediacy of Fe(I) complexes. Chem. Sci. 4, 1098–1104 (2013).

    Article  Google Scholar 

  35. Adams, C. J. et al. Iron(I) in Negishi cross-coupling reactions. J. Am. Chem. Soc. 134, 10333–10336 (2012).

    Article  CAS  PubMed  Google Scholar 

  36. Hill, D. H., Parvez, M. A. & Sen, A. Mechanistic aspects of the reaction of anionic iron(0)–olefin complexes with organic halides. Detection and characterization of paramagnetic organometallic intermediates. J. Am. Chem. Soc. 116, 2889–2901 (1994).

    Article  CAS  Google Scholar 

  37. Cheung, C.-W., Zhurkin, F. E. & Hu, X.-L. Z-Selective olefin synthesis via iron-catalyzed reductive coupling of alkyl halides with terminal arylalkynes. J. Am. Chem. Soc. 137, 4932–4935 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fleischauer, V. E., Muñoz, S. B. III, Neate, P. G. N., Brennessel, W. W. & Neidig, M. M. NHC and nucleophile chelation effects on reactive iron(II) species in alkyl–alkyl cross-coupling. Chem. Sci. 9, 1878–1891 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rummelt, S. M., Peterson, P. O., Zhong, H. Y. & Chirik, P. J. Oxidative addition of aryl and alkyl halides to a reduced iron pincer complex. J. Am. Chem. Soc. 143, 5928–5936 (2021).

    Article  CAS  PubMed  Google Scholar 

  40. Liu, J., Ye, Y., Sessler, J. L. & Gong, H. Cross-electrophile couplings of activated and sterically hindered halides and alcohol derivatives. Acc. Chem. Res. 53, 1833–1845 (2020).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  42. Harris, J. D., Oelkers, A. B. & Tyler, D. R. The solvent cage effect: is there a spin barrier to recombination of transition metal radicals? J. Am. Chem. Soc. 129, 6255–6262 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Barry, J. T., Berg, D. J. & Tyler, D. R. Radical cage effects: the prediction of radical cage pair recombination efficiencies using microviscosity across a range of solvent types. J. Am. Chem. Soc. 139, 14399–14405 (2017).

    Article  CAS  PubMed  Google Scholar 

  44. Yu, X.-L., Zheng, H.-L., Zhao, H.-N., Lee, B. C. & Koh, M. J. Iron-catalyzed regioselective alkenylboration of olefins. Angew. Chem. Int. Ed. 60, 2104–2109 (2021).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  46. Liu, J.-D. & Gong, H. Stereoselective preparation of α‑C‑vinyl/aryl glycosides via nickel-catalyzed reductive coupling of glycosyl halides with vinyl and aryl halides. Org. Lett. 20, 7991–7995 (2018).

    Article  CAS  PubMed  Google Scholar 

  47. 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).

    Article  CAS  Google Scholar 

  48. Mou, Z.-D., Wang, J.-X. & Niu, D. W. Stereoselective preparation of C-aryl glycosides via visible-light-induced nickel-catalyzed reductive cross-coupling of glycosyl chlorides and aryl bromides. Adv. Synth. Catal. 363, 3025–3029 (2021).

    Article  CAS  Google Scholar 

  49. Kim, S., Goldfogel, M. J., Gilbert, M. M. & Weix, D. J. Nickel-catalyzed cross-electrophile coupling of aryl chlorides with primary alkyl chlorides. J. Am. Chem. Soc. 142, 9902–9907 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Olivares, A. M. & Weix, D. J. Multimetallic Ni- and Pd-catalyzed cross-electrophile coupling to form highly substituted 1,3-dienes. J. Am. Chem. Soc. 140, 2446–2449 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Huang, L., Ackerman, L. K. G., Kang, K., Parsons, A. M. & Weix, D. J. LiCl-accelerated multimetallic cross-coupling of aryl chlorides with aryl triflates. J. Am. Chem. Soc. 141, 10978–10983 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kang, K., Huang, L. & Weix, D. J. Sulfonate versus sulfonate: nickel and palladium multimetallic cross-electrophile coupling of aryl triflates with aryl tosylates. J. Am. Chem. Soc. 142, 10634–10640 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li, M. et al. Visible-light-induced Pd-catalyzed radical strategy for constructing C-vinyl glycosides. Org. Lett. 22, 6288–6293 (2020).

    Article  CAS  PubMed  Google Scholar 

  54. Ghosh, S. & Pradhan, T. K. Stereoselective total synthesis of (+)-varitriol, (–)-varitriol, 5′-epi-(+)-varitriol, and 4′-epi-(–)-varitriol from d-mannitol. J. Org. Chem. 75, 2107–2110 (2010).

    Article  CAS  PubMed  Google Scholar 

  55. Sánchez-Eleuterio, A., García-Santos, W. H., Díaz-Salazar, H., Hernández-Rodríguez, M. & Cordero-Vargas, A. Stereocontrolled nucleophilic addition to five-membered oxocarbenium ions directed by the protecting groups. Application to the total synthesis of (+)-varitriol and of two diastereoisomers thereof. J. Org. Chem. 82, 8464–8475 (2017).

    Article  PubMed  Google Scholar 

  56. Koh, M. J., Nguyen, T. T., Zhang, H.-M., Schrock, R. R. & Hoveyda, A. H. Direct synthesis of Z-alkenyl halides through catalytic cross-metathesis. Nature 531, 459–465 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gillis, E. P., Eastman, K. J., Hill, M. D., Donnelly, D. J. & Meanwell, N. A. Applications of fluorine in medicinal chemistry. J. Med. Chem. 58, 8315–8359 (2015).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  59. Düfert, M. A., Billingsley, K. L. & Buchwald, S. L. Suzuki–Miyaura cross-coupling of unprotected, nitrogen-rich heterocycles: substrate scope and mechanistic investigation. J. Am. Chem. Soc. 135, 12877–12885 (2013).

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  61. Kusunuru, A. K., Tatina, M., Yousuf, S. K. & Mukherjee, D. Copper mediated stereoselective synthesis of C-glycosides from unactivated alkynes. Commun. Chem. 49, 10154–10156 (2013).

    Article  CAS  Google Scholar 

  62. Wilkinson, B. L., Bornaghi, L. F., Poulsen, S.-A. & Houston, T. A. Synthetic utility of glycosyl triazoles in carbohydrate chemistry. Tetrahedron. 62, 8115–8125 (2006).

    Article  CAS  Google Scholar 

  63. Hatakeyama, T., Hashimoto, S., Ishizuka, K. & Nakamura, M. Highly selective biaryl cross-coupling reactions between aryl halides and aryl Grignard reagents: a new catalyst combination of N-heterocyclic carbenes and iron, cobalt, and nickel fluorides. J. Am. Chem. Soc. 131, 11949–11963 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Prier, C. K. & MacMillan, D. W. Amine α-heteroarylation via photoredox catalysis: a homolytic aromatic substitution pathway. Chem. Sci. 5, 4173–4178 (2014).

    Article  CAS  PubMed  Google Scholar 

  65. Masuda, K., Nagatomo, M. & Inoue, M. Direct assembly of multiply oxygenated carbon chains by decarbonylative radical–radical coupling reactions. Nat. Chem. 9, 207–212 (2016).

    Article  PubMed  Google Scholar 

  66. Igarashi, K. The Koenigs–Knorr reaction. Adv. Carbohydr. Chem. Biochem. 34, 243–283 (1977).

    Article  CAS  Google Scholar 

  67. Li, M. et al. Transition-metal-free chemo- and regioselective vinylation of azaallyls. Nat. Chem. 9, 997–1004 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Yu, Y., Smith, J. M., Flaschenriem, C. J. & Holland, P. L. Binding affinity of alkynes and alkenes to low-coordinate iron. Inorg. Chem. 45, 5742–5751 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Weidauer, M., Irran, E., Someya, C. I., Haberberger, M. & Enthaler, S. Nickel-catalyzed hydrodehalogenation of aryl halides. J. Organomet. Chem. 729, 53–59 (2013).

    Article  CAS  Google Scholar 

  70. Manzoor, A., Wienefeld, P., Baird, M. C. & Budzelaar, P. H. M. Catalysis of cross-coupling and homocoupling reactions of aryl halides utilizing Ni(0), Ni(I), and Ni(II) precursors; Ni(0) compounds as the probable catalytic species but Ni(I) compounds as intermediates and products. Organometallics 36, 3508–3519 (2017).

    Article  CAS  Google Scholar 

  71. Zhu, F. & Walczak, M. A. Stereochemistry of transition metal complexes controlled by the metallo-anomeric effect. J. Am. Chem. Soc. 142, 15127–15136 (2020).

    Article  CAS  PubMed  Google Scholar 

  72. Dugave, C. & Demange, L. cis−trans isomerization of organic molecules and biomolecules: implications and applications. Chem. Rev. 103, 2475–2532 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Gaspari, R., Prota, A. E., Bargsten, K., Cavalli, A. & Steinmetz, M. O. Structural basis of cis- and trans-combretastatin binding to tubulin. Chem 2, 102–113 (2017).

    Article  CAS  Google Scholar 

  74. Lu, X. et al. Nickel-catalyzed defluorinative reductive cross-coupling of gem-difluoroalkenes with unactivated secondary and tertiary alkyl halides. J. Am. Chem. Soc. 139, 12632–12637 (2017).

    Article  CAS  PubMed  Google Scholar 

  75. Pu, L. & Yu, H.-B. Catalytic asymmetric organozinc additions to carbonyl compounds. Chem. Rev. 101, 757–824 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Wang, G.-Y. et al. Synthesis and anti-influenza activity of pyridine, pyridazine, and pyrimidine C-nucleosides as favipiravir (T-705) analogues. J. Med. Chem. 59, 4611–4624 (2016).

    Article  CAS  PubMed  Google Scholar 

  77. Koester, D. C., Kriemen, E. & Werz, D. B. Flexible synthesis of 2-deoxy-C-glycosides and (1→2)-, (1→3)-, and (1→4)-linked C-glycosides. Angew. Chem. Int. Ed. 52, 2985–2989 (2013).

    Article  CAS  Google Scholar 

  78. Enthaler, S., Junge, K. & Beller, M. Sustainable metal catalysis with iron: from rust to a rising star? Angew. Chem. Int. Ed. 47, 3317–3321 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Research Scholarship Block from the Ministry of Education, Singapore: C-143-000-207-532, C-141-000-777-532 and C-141-000-333-532 (M.J.K.), and NSFC-21725204 (G.C.). We thank G. K. Tan (National University of Singapore) for X-ray crystallographic analysis. We thank X.-X. Wang and X. Lu (University of Science and Technology of China) for assistance in preparing samples for the electron paramagnetic resonance experiments.

Author information

Author notes

  1. These authors contributed equally: Quanquan Wang, Qikai Sun.

  2. These authors jointly supervised this work: Gong Chen & Ming Joo Koh.

Authors and Affiliations

  1. Department of Chemistry, National University of Singapore, Singapore, Republic of Singapore

    Quanquan Wang, Yi Jiang & Ming Joo Koh

  2. State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, China

    Qikai Sun, Huixing Zhang & Gong Chen

  3. High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China

    Lu Yu & Changlin Tian

  4. Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China

    Changlin Tian

Authors
  1. Quanquan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qikai Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huixing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lu Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Changlin Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ming Joo Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Q.W., Q.S., Y.J. and H.Z. developed the catalytic method. L.Y. and C.T. carried out the electron paramagnetic resonance experiments. M.J.K. and G.C. directed the investigations. M.J.K. wrote the manuscript with revisions provided by the other authors.

Corresponding authors

Correspondence to Gong Chen or Ming Joo Koh.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Synthesis thanks the anonymous reviewers for their contribution to the peer review of this work. Thomas West was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Additional information

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

Supplementary information

Supplementary Information

Supplementary Tables 1–16, Figs. 1–28, experimental data, synthesis and characterization data, NMR spectra, X-ray crystallographic data and references.

Supplementary Data 1

Crystallographic data for compound 6f.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Q., Sun, Q., Jiang, Y. et al. Iron-catalysed reductive cross-coupling of glycosyl radicals for the stereoselective synthesis of C-glycosides. Nat Synth 1, 235–244 (2022). https://doi.org/10.1038/s44160-022-00024-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s44160-022-00024-5

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