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Iron(III)-based metalloradical catalysis for asymmetric cyclopropanation via a stepwise radical mechanism

Nature Chemistry volume 15, pages 1569–1580 (2023)Cite this article

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Abstract

Metalloradical catalysis (MRC) exploits the metal-centred radicals present in open-shell metal complexes as one-electron catalysts for the generation of metal-stabilized organic radicals—key intermediates that control subsequent one-electron homolytic reactions. Cobalt(II) complexes of porphyrins, as stable 15e-metalloradicals with a well-defined low-spin d7 configuration, have dominated the ongoing development of MRC. Here, to broaden MRC beyond the use of Co(II)-based metalloradical catalysts, we describe systematic studies that establish the operation of Fe(III)-based MRC and demonstrate an initial application for asymmetric radical transformations. Specifically, we report that five-coordinate iron(III) complexes of porphyrins with an axial ligand, which represent another family of stable 15e-metalloradicals with a d5 configuration, are potent metalloradical catalysts for olefin cyclopropanation with different classes of diazo compounds via a stepwise radical mechanism. This work lays a foundation and mechanistic blueprint for future exploration of Fe(III)-based MRC towards the discovery of diverse stereoselective radical reactions.

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Fig. 1: Proposed stepwise radical mechanism for cyclopropanation of alkenes with in situ-generated α-trifluoromethyldiazomethane via Fe(III)-based metalloradical catalysis.
Fig. 2: Comparative studies on catalytic cyclopropanation and detection of intermediates by HRMS to probe the oxidation state of iron porphyrin catalysts.
Fig. 3: DFT calculations on the catalytic mechanism for olefin cyclopropanation by [Fe(P3)Cl].
Fig. 4: Determination of iron spin states in [Fe(Por)Cl].
Fig. 5: Experimental studies on the catalytic mechanism of olefin cyclopropanation by the Fe(III)-based metalloradical system.

Data availability

All data are available in the main text or the Supplementary Information. The crystal structure data of compounds [Fe(P2)Cl], 1, (R)-3n, (1R,2R)-3ac, 8′ and 9 have been deposited in the Cambridge structural database under reference nos. CCDC 2128685, 2128686, 2128688, 2128687, 2128689 and 2043165, respectively. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

We are grateful for financial support by the NSF (CHE-2154885) and in part by NIH (R01-GM102554). W.-C.C.L. was supported by a LaMattina Graduate Fellowship and Dean’s Dissertation Fellowship. We thank B. Li (Boston College) for X-ray structure determination, J. Jin (Boston College) for EPR measurements, M. Graf (Boston College) for SQUID measurements and M. Kumar (Massachusetts Institute of Technology) for HRMS measurements. We thank J. Zhang (Johns Hopkins University) for helpful discussions and valuable suggestions. We also acknowledge financial support by NIH (S10-OD026910) and NSF (CHE-2117246) for the purchase of NMR spectrometers at the Magnetic Resonance Center of Boston College.

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Authors and Affiliations

  1. Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA, USA

    Wan-Chen Cindy Lee, Duo-Sheng Wang, Yiling Zhu & X. Peter Zhang

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Contributions

W.-C.C.L. conducted the experiments. D.-S.W. and Y.Z. performed the DFT calculations. X.P.Z. conceived the work and directed the project. W.-C.C.L. and X.P.Z. designed the experiments and wrote the manuscript.

Corresponding author

Correspondence to X. Peter Zhang.

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Nature Chemistry thanks Buddhadeb Chattopadhyay 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 information on experimental methods, synthetic procedures and compound characterizations, additional discussion, computational details, X-ray crystallographic data, NMR spectra and HPLC traces.

Supplementary Data 1

Crystallographic data for catalyst [Fe(P2)Cl]; CCDC reference 2128685.

Supplementary Data 2

Crystallographic data for compound 1; CCDC reference 2128686.

Supplementary Data 3

Crystallographic data for compound 3n; CCDC reference 2128688.

Supplementary Data 4

Crystallographic data for compound 3ac; CCDC reference 2128687.

Supplementary Data 5

Crystallographic data for compound 8′; CCDC reference 2128689.

Supplementary Data 6

Crystallographic data for compound 9; CCDC reference 2043165.

Supplementary Data 7

Energies and coordinates in XYZ format of DFT computations.

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Lee, WC.C., Wang, DS., Zhu, Y. et al. Iron(III)-based metalloradical catalysis for asymmetric cyclopropanation via a stepwise radical mechanism. Nat. Chem. 15, 1569–1580 (2023). https://doi.org/10.1038/s41557-023-01317-8

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