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Room temperature photo-promoted iron-catalysed arene C–H alkenylation without Grignard reagents

Nature Catalysis volume 7, pages 273–284 (2024)Cite this article

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Abstract

Iron is inexpensive, non-toxic and the most abundant transition metal in the Earth’s crust, rendering iron-catalysed C–H activations attractive yet particularly challenging. Despite major advances, iron-catalysed C–H activations have been linked to high reaction temperatures or the use of reactive Grignard reagents. Here we present iron-catalysed ketimine C–H activations at ambient reaction temperature with the help of blue light in the absence of additives, utilizing easily accessible cis-[Fe(H)2(dppe)2] (where dppe is 1,2-bis(diphenylphosphino)ethane) as a single component precatalyst. Mild reaction conditions, high atom economy and the lack of Grignard reagents are distinguishing features of the iron-catalysed C–H alkenylation manifold. Detailed mechanistic investigations by deuterium labelling, isolation of organometallic intermediates and in operando light-emitting diode nuclear magnetic resonance spectroscopy revealed the role of the light and an oxidative addition to an iron(0) complex as the modus operandi for the C–H activation.

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Fig. 1: Development of strategies for C–H activation of aromatic imines.
Fig. 2: Optimization of the photo-promoted iron-catalysed C–H activation.
Fig. 3: Scope for photo-promoted iron-catalysed alkenylation of imines 1.
Fig. 4: Stoichiometric reactions with iron-dihydride precatalysts.
Fig. 5: In situ LED-NMR spectroscopy experiments.
Fig. 6: Deuterium labelling experiments.
Fig. 7: On/off experiments.
Fig. 8: Proposed mechanism for the photo-promoted iron-catalysed C–H activation of phenone imines with blue light.

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Data availability

The data supporting the findings of this study are available within the article and its Supplementary Information, or from the authors on reasonable request. Crystal structure data have been deposited at the Cambridge Crystallographic Data Centre (CCDC nos. 2192211–2192227 and 2280102–2280104), and crystallographic data are provided in Supplementary Information. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk. Spectroscopic and kinetic data that support the findings of this study are freely available in Zenodo data repository, with https://doi.org/10.5281/zenodo.10138296.

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Acknowledgements

Generous support by the DFG (SPP 1807 Gottfried-Wilhelm-Leibniz award to L.A.), the European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie grant agreement no. 895404 to A.M.M. and ERC advanced grant agreement no. 101021358 to L.A.) and FCI Kekulé Fellowship no. 110091 (T.v.M.) is gratefully acknowledged. We thank C. Golz (Göttingen University) for assistance with the X-ray diffraction analysis and I. Maksso for measuring inductively coupled plasma mass spectrometry solutions.

Author information

Authors and Affiliations

  1. Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Göttingen, Germany

    Antonis M. Messinis, Tristan von Münchow, Max Surke & Lutz Ackermann

  2. Wöhler-Research Institute for Sustainable Chemistry, Georg-August-Universität Göttingen, Göttingen, Germany

    Antonis M. Messinis, Tristan von Münchow & Lutz Ackermann

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  1. Antonis M. Messinis
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Contributions

A.M.M. unravelled the photo-promoted iron-catalysed C–H activation of imines, conducted the mechanistic studies, explored the substrate scope assisted by T.v.M. and M.S., and wrote the paper with revisions provided by the other authors. M.S. performed the Grignard studies. L.A. conceived and directed the research programme and revised the paper.

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Correspondence to Lutz Ackermann.

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Nature Catalysis thanks Brian Patrick and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–52, Tables 1–6 and References.

Supplementary Data 1

CIF file of the crystal structure of compound 4a.

Supplementary Data 2

CIF file of the crystal structure of compound 4b.

Supplementary Data 3

CIF file of the crystal structure of compound 4c.

Supplementary Data 4

CIF file of the crystal structure of compound 4d.

Supplementary Data 5

CIF file of the crystal structure of compound 4e.

Supplementary Data 6

CIF file of the crystal structure of compound 4f.

Supplementary Data 7

CIF file of the crystal structure of compound 4g.

Supplementary Data 8

CIF file of the crystal structure of compound 5a.

Supplementary Data 9

CIF file of the crystal structure of compound 5b.

Supplementary Data 10

CIF file of the crystal structure of compound 5c.

Supplementary Data 11

CIF file of the crystal structure of compound 6a.

Supplementary Data 12

CIF file of the crystal structure of compound 6b.

Supplementary Data 13

CIF file of the crystal structure of compound 6c.

Supplementary Data 14

CIF file of the crystal structure of compound 8.

Supplementary Data 15

CIF file of the crystal structure of compound 10a.

Supplementary Data 16

CIF file of the crystal structure of compound 10b.

Supplementary Data 17

CIF file of the crystal structure of compound E-3aa.

Supplementary Data 18

CIF file of the crystal structure of compound E-3aa″.

Supplementary Data 19

CIF file of the crystal structure of compound E-3aj.

Supplementary Data 20

CIF file of the crystal structure of compound Z-3ea.

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Messinis, A.M., von Münchow, T., Surke, M. et al. Room temperature photo-promoted iron-catalysed arene C–H alkenylation without Grignard reagents. Nat Catal 7, 273–284 (2024). https://doi.org/10.1038/s41929-023-01105-0

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