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Photoredox catalysis with aryl sulfonium salts enables site-selective late-stage fluorination

Nature Chemistry volume 12, pages 56–62 (2020)Cite this article

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Abstract

Photoredox catalysis, especially in combination with transition metal catalysis, can produce redox states of transition metal catalysts to facilitate challenging bond formations that are not readily accessible in conventional redox catalysis. For arene functionalization, metallophotoredox catalysis has successfully made use of the same leaving groups as those valuable in conventional cross-coupling catalysis, such as bromide. Yet the redox potentials of common photoredox catalysts are not sufficient to reduce most aryl bromides, so synthetically useful aryl radicals are often not directly available. Therefore, the development of a distinct leaving group more appropriately matched in redox potential could enable new reactivity manifolds for metallophotoredox catalysis, especially if arylcopper(iii) complexes are accessible, from which the most challenging bond-forming reactions can occur. Here we show the conceptual advantages of aryl thianthrenium salts for metallophotoredox catalysis, and their utility in site-selective late-stage aromatic fluorination.

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Fig. 1: Metallophotoredox-catalysis-enabled functionalization of arenes.
Fig. 2: Mechanism.
Fig. 3: Mechanism experiments.

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Data availability

Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers CCDC 1900278 (4), 1900279 (25-TT), 1900280 (40-TT), 1900276 (41-TT) and 1900277 (43-TT) (Supplementary Figs. 42–46). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. All other data that support the findings of this study are available within the article and its Supplementary Information, or from the corresponding author upon reasonable request.

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Acknowledgements

We thank C. Costentin (Université Paris VII) for helpful discussions on the electrochemical analysis. We thank O. Rüdiger (MPI CEC) for providing the electrochemical set-up and for helpful discussions, S. Marcus and D. Kampen (MPI KOFO) for mass spectrometry analysis and A. Dreier and J. Rust (MPI KOFO) for the crystal structure analysis.

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Authors and Affiliations

  1. Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany

    Jiakun Li, Junting Chen, Ruocheng Sang, Won-Seok Ham, Matthew B. Plutschack, Florian Berger & Tobias Ritter

  2. Max-Planck-Institut für Chemische Energiekonversion, Mülheim an der Ruhr, Germany

    Sonia Chabbra & Alexander Schnegg

  3. Global Chemistry, UCB Biopharma SPRL, Braine-l’Alleud, Belgium

    Christophe Genicot

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Contributions

J.L., J.C. and R.S. developed the fluorination reaction. W.-S.H., M.B.P, J.L., J.C., F.B., S.C., A.S. and C.G. contributed to the mechanistic studies. F.B. initiated the approach to the project. All the authors wrote the manuscript. T.R. directed the project.

Corresponding author

Correspondence to Tobias Ritter.

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Competing interests

A patent application (German patent number EP18204755.5), dealing with the use of TT and its derivatives for C–H functionalization has been filed, and F.B. and T.R. may benefit from royalty payments.

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Supplementary information

Supplementary information

Experimental procedures, product characterization, X-ray crystallographic analysis and mechanistic studies.

Crystallographic data

Crystallographic data for compound 25-TT. CCDC reference 1900279

Crystallographic data

Crystallographic data for compound 4. CCDC reference 1900278

Crystallographic data

Crystallographic data for compound 41-TT. CCDC reference 1900276

Crystallographic data

Crystallographic data for compound 43-TT. CCDC reference 1900277

Crystallographic data

Crystallographic data for compound 40-TT. CCDC reference 1900280

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Li, J., Chen, J., Sang, R. et al. Photoredox catalysis with aryl sulfonium salts enables site-selective late-stage fluorination. Nat. Chem. 12, 56–62 (2020). https://doi.org/10.1038/s41557-019-0353-3

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