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.
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Iron-mediated ligand-to-metal charge transfer enables 1,2-diazidation of alkenes
Nature Communications Open Access 23 December 2022
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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/.
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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.
The authors declare no competing interests.
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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.
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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
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