Abstract
Linkage chemistry and functional molecules derived from the stereogenic sulfur(VI) centre have important applications in organic synthesis, bioconjugation, drug discovery, agrochemicals and polymeric materials. However, existing approaches for the preparation of optically active S(VI)-centred compounds heavily rely on synthetic chiral S(IV) pools, and the reported linkers of S(VI) lack stereocontrol. A modular assembly method, involving sequential ligand exchange at the S(VI) centre with precise control of enantioselectivity, is appealing but remains elusive. Here we report an asymmetric three-dimensional sulfur(VI) fluoride exchange (3D-SuFEx) reaction based on thionyl tetrafluoride gas (SOF4). A key step involves the chiral ligand-induced enantioselective defluorinative substitution of iminosulfur oxydifluorides using organolithium reagents. The resulting optically active sulfonimidoyl fluorides allow for further stereospecific fluoride-exchange by various nucleophiles, thereby establishing a modular platform for the asymmetric SuFEx ligation and the divergent synthesis of optically active S(VI) functional molecules.
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Data availability
All relevant data supporting the findings of this study, including experimental procedures and compound characterization, are available within the article and its supplementary information. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2128746 (1t), 2128749 ((R)-3ab), 2242977 ((S)-4b), 2128751 ((R)-4c) and 2128755 ((S)-4e). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.
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Acknowledgements
Financial support was provided by National Natural Science Foundation of China (22001065 to B.G., 22122104 to X.-S.X., 22193012 to X.-S.X. and 21933004 to X.-S.X.), the Science and Technology Foundation of Hunan Province (2021JJ30090 to B.G.), the Ministry of Science and Technology of China (2021YFF0701700 to X.-S.X. and 2021YFF0701704 to J.D.), J.D. is also thankful for the financial support from Shanghai Pilot Program for Basic Research, Shanghai Jiao Tong University and the WLA Laboratories. B.G. thanks K. B. Sharpless, P. Wu and J. Cappiello at Scripps Research for their generous support and helpful discussion.
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B.G. and J.D. conceived and directed the project. Z.P., S.S., Y.L., X.L., S.L. and B.G. conducted the experiments. M.-M.Z. and X.-S.X. conducted the DFT calculations. B.G. wrote the manuscript with the input from all authors.
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Nature Chemistry thanks Xuefeng Jiang, Patrick Melvin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Supplementary information
Supplementary Information
The supplementary information file contains 12 sections, covering the experimental procedure, synthesis and characterization data, NMR spectra, X-ray crystallographic data, DFT calculation and references.
Supplementary Data 1
Crystallographic data for compound (R)-3ab; CCDC reference 2128749.
Supplementary Data 2
Crystallographic data for compound (R)-4c; CCDC reference 2128751.
Supplementary Data 3
Crystallographic data for compound (S)-4b; CCDC reference 2242977.
Supplementary Data 4
Crystallographic data for compound (S)-4e; CCDC reference 2128755.
Supplementary Data 5
Crystallographic data for compound 1t; CCDC reference 2128746.
Supplementary Data 6
Structure factors for compound (R)-3ab; CCDC reference 2128749.
Supplementary Data 7
Structure factors for compound (R)-4c; CCDC reference 2128751.
Supplementary Data 8
Structure factors for compound (S)-4b; CCDC reference 2242977.
Supplementary Data 9
Structure factors for compound (S)-4e; CCDC reference 2128755.
Supplementary Data 10
Structure factors for compound 1t; CCDC reference 2128746.
Supplementary Data 11
Computational data for DFT calculations.
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Peng, Z., Sun, S., Zheng, MM. et al. Enantioselective sulfur(VI) fluoride exchange reaction of iminosulfur oxydifluorides. Nat. Chem. 16, 353–362 (2024). https://doi.org/10.1038/s41557-024-01452-w
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DOI: https://doi.org/10.1038/s41557-024-01452-w
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