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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.

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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/.

References

  1. Zard, S. Z. Radical Reactions in Organic Synthesis (Oxford Chemistry Masters, 2003).

  2. Curran, D. P., Porter, N. A. & Giese, B. Stereochemistry of Radical Reactions: Concepts, Guidelines and Synthetic Applications (Wiley, 2008).

  3. Bar, G. & Parsons, A. F. Stereoselective radical reactions. Chem. Soc. Rev. 32, 251–263 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Mondal, S. et al. Enantioselective radical reactions using chiral catalysts. Chem. Rev. 122, 5842–5976 (2022).

    Article  CAS  PubMed  Google Scholar 

  5. Kern, N., Plesniak, M. P., McDouall, J. J. W. & Procter, D. J. Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals. Nat. Chem. 9, 1198–1204 (2017).

    Article  CAS  PubMed  Google Scholar 

  6. Wang, F., Chen, P. H. & Liu, G. S. Copper-catalyzed radical relay for asymmetric radical transformations. Acc. Chem. Res. 51, 2036–2046 (2018).

    Article  CAS  PubMed  Google Scholar 

  7. Gu, Q. S., Li, Z. L. & Liu, X. Y. Copper(I)-catalyzed asymmetric reactions involving radicals. Acc. Chem. Res. 53, 170–181 (2020).

    Article  CAS  PubMed  Google Scholar 

  8. Li, Z. L., Fang, G. C., Gu, Q. S. & Liu, X. Y. Recent advances in copper-catalyzed radical-involved asymmetric 1,2-difunctionalization of alkenes. Chem. Soc. Rev. 49, 32–48 (2020).

    Article  CAS  PubMed  Google Scholar 

  9. Lee, W. C. C. & Zhang, X. P. Asymmetric radical cyclopropanation of alkenes. Trends Chem. 4, 850–851 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. van Leest, N. P., de Zwart, F. J., Zhou, M. & de Bruin, B. Controlling radical-type single-electron elementary steps in catalysis with redox-active ligands and substrates. JACS Au 1, 1101–1115 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rajanbabu, T. V. & Nugent, W. A. Selective generation of free-radicals from epoxides using a transition-metal radical. A powerful new tool for organic synthesis. J. Am. Chem. Soc. 116, 986–997 (1994).

    Article  CAS  Google Scholar 

  12. Funken, N., Muhlhaus, F. & Gansauer, A. General, highly selective synthesis of 1,3- and 1,4 difunctionalized building blocks by regiodivergent epoxide opening. Angew. Chem. Int. Ed. 55, 12030–12034 (2016).

    Article  CAS  Google Scholar 

  13. Yao, C. B., Dahmen, T., Gansauer, A. & Norton, J. Anti-Markovnikov alcohols via epoxide hydrogenation through cooperative catalysis. Science 364, 764–767 (2019).

    Article  CAS  PubMed  Google Scholar 

  14. Ye, K. Y., McCallum, T. & Lin, S. Bimetallic radical redox-relay catalysis for the isomerization of epoxides to allylic alcohols. J. Am. Chem. Soc. 141, 9548–9554 (2019).

    Article  CAS  PubMed  Google Scholar 

  15. Chan, Y. W. & Chan, K. S. Metalloradical-catalyzed aliphatic carbon−carbon activation of cyclooctane. J. Am. Chem. Soc. 132, 6920–6922 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Roy, S., Das, S. K. & Chattopadhyay, B. Cobalt(II)-based metalloradical activation of 2-(diazomethyl)-pyridines for radical transannulation and cyclopropanation. Angew. Chem. Int. Ed. 57, 2238–2243 (2018).

    Article  CAS  Google Scholar 

  17. Roy, S., Khatua, H., Das, S. K. & Chattopadhyay, B. Iron(II)-based metalloradical activation: switch from traditional click chemistry to denitrogenative annulation. Angew. Chem. Int. Ed. 58, 11439–11443 (2019).

    Article  CAS  Google Scholar 

  18. Das, S. K., Roy, S., Khatua, H. & Chattopadhyay, B. Iron-catalyzed amination of strong aliphatic C(sp3)–H bonds. J. Am. Chem. Soc. 142, 16211–16217 (2020).

    Article  CAS  PubMed  Google Scholar 

  19. Roy, S. et al. Road map for the construction of high-valued N-heterocycles via denitrogenative annulation. Acc. Chem. Res. 54, 4395–4409 (2021).

    Article  CAS  PubMed  Google Scholar 

  20. Roy, S. et al. Iron-catalyzed radical activation mechanism for denitrogenative rearrangement over C(sp3)–H amination. Angew. Chem. Int. Ed. 60, 8772–8780 (2021).

    Article  CAS  Google Scholar 

  21. Das, S. K. et al. An iron(II)-based metalloradical system for intramolecular amination of C(sp2)–H and C(sp3)–H bonds: synthetic applications and mechanistic studies. Chem. Sci. 13, 11817–11828 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee, W.-C. C. et al. Asymmetric radical cyclopropanation of dehydroaminocarboxylates: stereoselective synthesis of cyclopropyl α-amino acids. Chem 7, 1588–1601 (2021).

    Article  CAS  Google Scholar 

  23. Riart-Ferrer, X. et al. Metalloradical activation of carbonyl azides for enantioselective radical aziridination. Chem 7, 1120–1134 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Xie, J. J. et al. New catalytic radical process involving 1,4-hydrogen atom abstraction: asymmetric construction of cyclobutanones. J. Am. Chem. Soc. 143, 11670–11678 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lang, K., Hu, Y., Lee, W.-C. C. & Zhang, X. P. Combined radical and ionic approach for the enantioselective synthesis of β-functionalized amines from alcohols. Nat. Synth. 1, 548–557 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Woggon, W. D. Metalloporphyrines as active site analogues—lessons from enzymes and enzyme models. Acc. Chem. Res. 38, 127–136 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Oohora, K., Onoda, A. & Hayashi, T. Hemoproteins reconstituted with artificial metal complexes as biohybrid catalysts. Acc. Chem. Res. 52, 945–954 (2019).

    Article  CAS  PubMed  Google Scholar 

  28. Yang, Y. & Arnold, F. H. Navigating the unnatural reaction space: directed evolution of heme proteins for selective carbene and nitrene transfer. Acc. Chem. Res. 54, 1209–1225 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wolf, J. R. et al. Shape and stereoselective cyclopropanation of alkenes catalyzed by iron porphyrins. J. Am. Chem. Soc. 117, 9194–9199 (1995).

    Article  CAS  Google Scholar 

  30. Lai, T. S. et al. Alkene cyclopropanation catalyzed by Halterman iron porphyrin: participation of organic bases as axial ligands. Dalton Trans. 2006, 4845–4851 (2006).

    Article  Google Scholar 

  31. Aggarwal, V. K., de Vicente, J. & Bonnert, R. V. Catalytic cyclopropanation of alkenes using diazo compounds generated in situ. A novel route to 2-arylcyclopropylamines. Org. Lett. 3, 2785–2788 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Li, Y. et al. Remarkably stable iron porphyrins bearing nonheteroatom-stabilized carbene or (alkoxycarbonyl)carbenes: isolation, X-ray crystal structures, and carbon atom transfer reactions with hydrocarbons. J. Am. Chem. Soc. 124, 13185–13193 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Adams, L. A. et al. Diastereoselective synthesis of cyclopropane amino acids using diazo compounds generated in situ. J. Org. Chem. 68, 9433–9440 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Morandi, B. & Carreira, E. M. Iron-catalyzed cyclopropanation in 6 M KOH with in situ generation of diazomethane. Science 335, 1471–1474 (2012).

    Article  CAS  PubMed  Google Scholar 

  35. Morandi, B., Dolva, A. & Carreira, E. M. Iron-catalyzed cyclopropanation with glycine ethyl ester hydrochloride in water. Org. Lett. 14, 2162–2163 (2012).

    Article  CAS  PubMed  Google Scholar 

  36. Zhu, S. F. & Zhou, Q. L. Iron-catalyzed transformations of diazo compounds. Natl Sci. Rev. 1, 580–603 (2014).

    Article  CAS  Google Scholar 

  37. Allouche, E. M. D., Al-Saleh, A. & Charette, A. B. Iron-catalyzed synthesis of cyclopropanes by in situ generation and decomposition of electronically diversified diazo compounds. Chem. Commun. 54, 13256–13259 (2018).

    Article  CAS  Google Scholar 

  38. Ning, Y. Q. et al. Difluoroacetaldehyde N-triftosylhydrazone (DFHZ-Tfs) as a bench-stable crystalline diazo surrogate for diazoacetaldehyde and difluorodiazoethane. Angew. Chem. Int. Ed. 59, 6473–6481 (2020).

    Article  CAS  Google Scholar 

  39. Damiano, C., Sonzini, P. & Gallo, E. Iron catalysts with N-ligands for carbene transfer of diazo reagents. Chem. Soc. Rev. 49, 4867–4905 (2020).

    Article  CAS  PubMed  Google Scholar 

  40. Le Maux, P., Juillard, S. & Simonneaux, G. Asymmetric synthesis of trifluoromethylphenyl cyclopropanes catalyzed by chiral metalloporphyrins. Synthesis 2006, 1701–1704 (2006).

    Article  Google Scholar 

  41. Chen, Y. & Zhang, X. P. Asymmetric cyclopropanation of styrenes catalyzed by metal complexes of D2-symmetrical chiral porphyrin: superiority of cobalt over iron. J. Org. Chem. 72, 5931–5934 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Intrieri, D. et al. Highly diastereoselective cyclopropanation of α-methylstyrene catalysed by a C2-symmetrical chiral iron porphyrin complex. Chem. Commun. 50, 1811–1813 (2014).

    Article  CAS  Google Scholar 

  43. Carminati, D. M. et al. Designing ‘totem’ C2-symmetrical iron porphyrin catalysts for stereoselective cyclopropanations. Chem. Eur. J. 22, 13599–13612 (2016).

    Article  CAS  PubMed  Google Scholar 

  44. Carminati, D. M. et al. Synthesis, characterisation and catalytic use of iron porphyrin amino ester conjugates. New J. Chem. 41, 5950–5959 (2017).

    Article  CAS  Google Scholar 

  45. Bos, M. et al. Recent progress toward the synthesis of trifluoromethyl- and difluoromethyl-substituted cyclopropanes. Chem. Eur. J. 23, 4950–4961 (2017).

    Article  CAS  PubMed  Google Scholar 

  46. Mykhailiuk, P. K. 2,2,2-Trifluorodiazoethane (CF3CHN2): a long journey since 1943. Chem. Rev. 120, 12718–12755 (2020).

    Article  CAS  PubMed  Google Scholar 

  47. Decaens, J. et al. Synthesis of fluoro-, monofluoromethyl-, difluoromethyl- and trifluoromethyl-substituted three-membered rings. Chem. Eur. J. 27, 2935–2962 (2021).

    Article  CAS  PubMed  Google Scholar 

  48. Pons, A. et al. Asymmetric synthesis of fluoro, fluoromethyl, difluoromethyl and trifluoromethylcyclopropanes. Acc. Chem. Res. 54, 2969–2990 (2021).

    Article  CAS  PubMed  Google Scholar 

  49. Morandi, B. & Carreira, E. M. Iron-catalyzed cyclopropanation with trifluoroethylamine hydrochloride and olefins in aqueous media: in situ generation of trifluoromethyl diazomethane. Angew. Chem. Int. Ed. 49, 938–941 (2010).

    Article  CAS  Google Scholar 

  50. Morandi, B., Cheang, J. & Carreira, E. M. Iron-catalyzed preparation of trifluoromethyl substituted vinyl- and alkynylcyclopropane. Org. Lett. 13, 3080–3081 (2011).

    Article  CAS  PubMed  Google Scholar 

  51. Phelan, J. P. et al. Redox-neutral photocatalytic cyclopropanation via radical/polar crossover. J. Am. Chem. Soc. 140, 8037–8047 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang, X. Y. et al. Use of trifluoroacetaldehyde N-tfsylhydrazone as a trifluorodiazoethane surrogate and its synthetic applications. Nat. Commun. 10, 284 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Denton, J. R., Sukumaran, D. & Davies, H. M. L. Enantioselective synthesis of trifluoromethyl-substituted cyclopropanes. Org. Lett. 9, 2625–2628 (2007).

    Article  CAS  PubMed  Google Scholar 

  54. Zhang, X. Y. et al. Fluoroalkyl N-triftosylhydrazones as easily decomposable diazo surrogates for asymmetric [2 + 1] cycloaddition: synthesis of chiral fluoroalkyl cyclopropenes and cyclopropanes. ACS Catal. 11, 8527–8537 (2021).

    Article  CAS  Google Scholar 

  55. Huang, W. S. et al. General catalytic enantioselective access to monohalomethyl and trifluoromethyl cyclopropanes. Chem. Eur. J. 24, 10339–10343 (2018).

    Article  CAS  PubMed  Google Scholar 

  56. Pagire, S. K., Kumagai, N. & Shibasaki, M. Highly enantio- and diastereoselective synthesis of 1,2,3-trisubstituted cyclopropanes from α,β-unsaturated amides and stabilized sulfur ylides catalyzed by a chiral copper(I) complex. ACS Catal. 11, 11597–11606 (2021).

    Article  Google Scholar 

  57. Morandi, B., Mariampillai, B. & Carreira, E. M. Enantioselective cobalt-catalyzed preparation of trifluoromethyl-substituted cyclopropanes. Angew. Chem. Int. Ed. 50, 1101–1104 (2011).

    Article  CAS  Google Scholar 

  58. Tinoco, A., Steck, V., Tyagi, V. & Fasan, R. Highly diastereo- and enantioselective synthesis of trifluoromethyl-substituted cyclopropanes via myoglobin-catalyzed transfer of trifluoromethylcarbene. J. Am. Chem. Soc. 139, 5293–5296 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Carminati, D. M. et al. Biocatalytic strategy for the highly stereoselective synthesis of CHF2-containing trisubstituted cyclopropanes. Angew. Chem. Int. Ed. 60, 7072–7076 (2021).

    Article  CAS  Google Scholar 

  60. Kotozaki, M. et al. Highly enantioselective synthesis of trifluoromethyl cyclopropanes by using Ru(II)–Pheox catalysts. Chem. Commun. 54, 5110–5113 (2018).

    Article  CAS  Google Scholar 

  61. Altarejos, J., Sucunza, D., Vaquero, J. J. & Carreras, J. Enantioselective copper-catalyzed synthesis of trifluoromethyl-cyclopropylboronates. Org. Lett. 23, 6174–6178 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chen, Y., Fields, K. B. & Zhang, X. P. Bromoporphyrins as versatile synthons for modular construction of chiral porphyrins: cobalt-catalyzed highly enantioselective and diastereoselective cyclopropanation. J. Am. Chem. Soc. 126, 14718–14719 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Xu, X. et al. Highly asymmetric intramolecular cyclopropanation of acceptor-substituted diazoacetates by Co(II)-based metalloradical catalysis: iterative approach for development of new-generation catalysts. J. Am. Chem. Soc. 133, 15292–15295 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Kweon, J. & Chang, S. Highly robust iron catalyst system for intramolecular C(sp3)–H amidation leading to γ-lactams. Angew. Chem. Int. Ed. 60, 2909–2914 (2021).

    Article  CAS  Google Scholar 

  65. Nakamura, M. Electronic structures of highly deformed Iron(III) porphyrin complexes. Coord. Chem. Rev. 250, 2271–2294 (2006).

    Article  CAS  Google Scholar 

  66. Nakamura, M. in Fundamentals of Porphyrin Chemistry: A 21st Century Approach (eds Brothers, P. J. & Senge, M. O.) 631–659 (Wiley, 2022).

  67. Cheng, R. J. et al. Control of spin state by ring conformation of Iron(III) porphyrins. A novel model for the quantum-mixed intermediate spin state of ferric cytochrome c′ from photosynthetic bacteria. J. Am. Chem. Soc. 119, 2563–2569 (1997).

    Article  CAS  Google Scholar 

  68. Stuzhin, P. A. et al. Effects of solvation on the spin state of Iron(III) in 2,8,12,18-tetrabutyl-3,7,13,17-tetramethyl-5,10-diazaporphyrinatoiron(III) chloride. Inorg. Chem. 49, 4802–4813 (2010).

    Article  CAS  PubMed  Google Scholar 

  69. Sahoo, D., Quesne, M. G., de Visser, S. P. & Rath, S. P. Hydrogen-bonding interactions trigger a spin-flip in Iron(III) porphyrin complexes. Angew. Chem. Int. Ed. 54, 4796–4800 (2015).

    Article  CAS  Google Scholar 

  70. Wei, Y. et al. Cyclopropanations via heme carbenes: basic mechanism and effects of carbene substituent, protein axial ligand, and porphyrin substitution. J. Am. Chem. Soc. 140, 1649–1662 (2018).

    Article  CAS  PubMed  Google Scholar 

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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.

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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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