C_sp²–H/F bond activation and borylation with iron

Abstract

Reduction of [K₂{(^tBupyrr₂pyr)Fe}₂(μ-N₂)] (1) with two equiv. of KC₈ in the presence of crown-ether 18-C-6 yields the N₂ adduct [{K(18-C-6)}₂(^tBupyrr₂pyr)Fe(N₂)] (2). Complex 2 heterolytically splits the C_sp²–H bond of benzene to form [{K(18-C-6)}(^tBupyrr₂pyr)Fe(C₆H₅)] (3), whereby usage of a diboron B₂pin₂ promotes hydride elimination to form the salt [K(18-C-6)HB₂Pin₂] (4). Similarly, 3 can also be formed by cleavage of the C–F bond of fluorobenzene. Reaction of 3 with ClBcat yields [K(18-C-6)(thf)₂][(^tBupyrr₂pyr)FeCl] (5) and PhBcat and the former can be reduced to 2 to complete a synthetic cycle for heterolytic benzene C–H activation and borylation.

---

The activation and functionalization of C–H bonds is a crucial step toward converting an unreactive and abundant substrate into more reactive or synthetically versatile functionalities.¹ Much of the early literature on C–H activation focuses on the oxidative addition of C–H bonds at low valent precious metals.² This research was performed in the context of cross-coupling reactions which typically go through catalytic cycles consisting of oxidative addition, transmetallation, and reductive elimination.³ A particularly useful target for C–H functionalization would be the generation of C–B bonds due to their prevalence in Suzuki–Miyaura cross coupling reactions.⁴ While C–H activation is usually accomplished with precious metals, there is precedent for this reaction at iron,⁵ which is the most abundant metal in Earth's crust.⁶ To this end, borylation of aryl C_sp²–H bonds by photolysis of an iron boryl species has been reported,⁷ with more recent studies expanding this work to catalytic processes for C–H borylation.⁸ While mechanistic studies for arene C–H borylation reactions have been studied in detail with first row transition metals such as Co,⁹ similar studies clearly showing the bond forming and breaking processes at the Fe center have been exceptionally rare.^{5e,7b,7c,8a,8j,10}

In this contribution, we show how a formally Fe⁰ and mononuclear Fe dinitrogen complex [{K(18-C-6)}₂(^tBupyrr₂pyr)Fe(N₂)] (2) (^tBupyrr₂pyr²⁻ = 3,5-^tBu₂-bis(pyrrolyl)pyridine; 18-C-6 = 18-crown-6) can activate the C_sp²–H bond of benzene (and the C–F bond of fluorobenzene) at room temperature to yield the ferrous phenyl complex [{K(18-C-6)}(^tBupyrr₂pyr)Fe(C₆H₅)] (3). We propose the C–H activation process to be heterolytic in nature by trapping KH with B₂pin₂ (pin = pinacolato) to form the adduct [K(18-C-6)HB₂pin₂] (4). The aryl ligand from 3 can be transmetallated using ClBcat (cat = catecholato) to yield the discrete salt [{K(18-C-6)(thf)₂}(^tBupyrr₂pyr)FeCl] (5) along with the borane PhBcat (6). Finally, we show how 5 can be reduced to 2 to close a synthetic cycle for room temperature C_sp²–X bond activation and borylation (Scheme 1).

Scheme 1 Reaction scheme outlining formation and reactions of [{K(18-C-6)}₂(^tBupyrr₂pyr)Fe(N₂)] (2).

We have previously shown that reduction of the ferrous precursor [(^tBupyrr₂pyr)Fe(OEt₂)]¹¹ with one equiv. of KC₈ yields the formally Fe^I end-on and bridging N₂ complex [K₂{(^tBupyrr₂pyr)Fe}₂(μ-N₂)] (1) in which the N₂ ligand bridging the two Fe centers is topologically nonlinear.¹² Such a geometry is retained upon further reduction to the formally Fe⁰ complex [{K₂(18-C-6)}{(^tBupyrr₂pyr)Fe}₂(μ-N₂)] or via oxidative substitution of N₂ with chalcogenides.¹³ The full extent of low oxidation state iron chemistry using the ^tBupyrr₂pyr ligand platform, especially as it pertains to mononuclear complexes, has so far been unexplored. Treatment of 1 equiv. of 1 with four equivalents of 18-C-6 and two equivalents of KC₈ in toluene at room temperature resulted in the initial formation of a brown residue. Allowing the reaction to stir for an additional hour at room temperature led to the conversion of the brown residue to a dark purple solution. After filtration and concentration in vacuo, the solution was cooled to −35 °C overnight to afford [{K(18-C-6)}₂(^tBupyrr₂pyr)Fe(N₂)] (2), which could be isolated in 79% yield as dark crystals (Scheme 1 and Fig. 1). The ¹H NMR spectrum of 2 shows seven paramagnetically broadened and shifted resonances indicative of a C_s symmetric system (Fig. S1, ESI†). A single-crystal X-ray diffraction study (sc-XRD) of 2 shows a (^tBupyrr₂pyr)Fe scaffold with a terminal N₂ ligand occupying the fourth coordination site and capped by a {K(18-C-6)}⁺ unit. The second {K(18-C-6)}⁺ is coordinated to the pyridyl portion of the meridional ligand. The geometry at the formally Fe(0) center in 2 can best be described as seesaw with a ∠N_pyr–Fe–N₂ angle of 140.7(2)° and a τ₄ value of 0.51. The N₂ ligand has an N–N bond length of 1.147(6) Å and a signature stretch at 1851 cm⁻¹ in the IR spectrum (Fig. S21, ESI†) implying significant activation of the N₂ ligand when compared to its free form (1.0975 Å, 2331 cm⁻¹).¹⁴ The low energy vibration and elongated N–N bond for the N₂ ligand implies not only the metal ion but the N₂ ligand to be the likely locus of reduction.¹⁵ While we cannot determine the Fe oxidation state of 2 with complete certainty, a significantly shortened Fe–N₂ bond length of 1.775(4) Å and solution state magnetic moment of 4.1 μ_B, measured by Evans Method in C₆D₆, which is above the expectation value for an S = 1 system, and implies contribution of a Fe^I atom and N₂-centered radical to the complicated electronic structure. In contrast to the bridging nature of [{K₂(18-C-6)(^tBupyrr₂pyr)Fe}₂(μ-N₂)], we propose the mononuclear structure of 2 to derive from the addition of more equivalents of 18-crown-6.

Fig. 1 ORTEP sc-XRD structures of complexes 2, 3, 4, and 5 at 50% probability level. Residual solvent molecules and H atoms (with the exception of the hydride in compound 4) have been omitted for clarity. Coordinated thf molecules coordinated to K⁺ in compound 5 have been also omitted for clarity.

Interested in the oxidative chemistry of 2, we treated this species with one equivalent of bispinacolato diboron (B₂pin₂) in benzene expecting to observe reductive cleavage of the B–B bond. However, upon addition of the B₂pin₂, the reaction mixture gradually changed color from dark purple to red, and over 16 hours there was deposition of red crystals. A sc-XRD study on a single-crystal isolated from the reaction mixture confirms the structure to be instead the discrete phenyl salt [{K(18-C-6)}(^tBupyrr₂pyr)Fe(C₆H₅)] (3) which was isolated in 61% yield. The solid-state structure of 3 shows a formally Fe^II ion with an Fe–C bond length of 2.068(1) Å resulting from benzene C–H activation. The ∠N_pyr–Fe–C_Ar angle is 123.88(5)° and the geometric index value of τ₄ = 0.74 is consistent with a distorted cis-divacant octahedral coordination geometry. A ¹H NMR spectroscopic study of these crystals in thf-d₈ shows 9 paramagnetically shifted and broadened resonances showing preservation of a C_s symmetric system in solution (Fig. S2, ESI†). A room temperature solution state magnetic moment of 4.8 μ_B, determined by Evans method, is close to the spin only value for an S = 2 system in accord with a high spin Fe^II ion in 3. Examination of the supernatant from the reaction between 2 and B₂Pin₂ by ¹¹B NMR spectroscopy in thf-d₈ revealed 2 resonances at 30.97 ppm and 5.91 ppm (Fig. S9, ESI†). Resonances in these positions can be attributed to one trigonal planar and one pyramidal B atom as demonstrated by Marder and coworkers in a series of [{K(18-crown-6)}XB₂pin₂] molecules, where X = O^tBu, OMe, and F.¹⁶ In our case, the B-containing molecule could be crystallized out of a concentrated thf solution at −35 °C and its structure determined to be [{K(18-crown-6)}HB₂pin₂] (4). A sc-XRD structure of 4 clearly shows a HB₂pin₂ core with two distinctly different B centers as well as a {K(18-C-6)}⁺ counter ion interacting with the hydride and nearby pinacolato oxygen (Fig. 1). ¹¹B NMR spectroscopy of the crystals also showed, as expected, 2 resonances, albeit at slightly different chemical shifts (Fig. S8, ESI†) when compared to the crude material. We attribute this discrepancy to the lack of paramagnetic impurities in the crystalline material contributing to a noncontact paramagnetic shift.¹⁷ Transfer of a hydrogen atom to a borane has been reported before in the context of C–H activation at low valent iron centers, but diboron reagents have not been used to sponge out the hydride most likely stemming from heterolytic C–H bond cleavage.^5e,5g Using other hydride acceptors such as imines and nitriles or other Lewis acids such as B(C₆F₅)₃ did not result in the formation of 3 (Fig. S13–S17, ESI†). We found that complex 3 could also be generated by reaction of 2 with fluorobenzene at room temperature (Scheme 1) in a manner similar to Holland's work using low valent Co complexes.¹⁸ Unfortunately, our reaction was not quantitative thus resulting in formation of other intractable materials (Fig. S10, ESI†). Selective C–F bond activation is rare¹⁹ and C–F bonds are known to be stable toward catalytic C–H borylation protocols.^8a,8c,8h,9c

Having demonstrated that 2 could undergo C–H activation of benzene we next turned to delivering or functionalizing the phenyl moiety of 3. Accordingly, treatment of 3 with one equivalent of ClBcat in thf-d₈ resulted in a new paramagnetic molecule when judged by ¹H NMR spectroscopy. ¹H and ¹¹B NMR spectroscopy confirmed that a second, diamagnetic species was formed, namely PhBCat (Fig. S19, ESI,† ¹¹B NMR δ = 32.6).²⁰ The paramagnetic product was identified to be [{K(18-C-6)(thf)₂}(^tBupyrr₂pyr)FeCl] (5) using a combination of ¹H NMR, sc-XRD, solution magnetic susceptibility studies, as well as by an independent synthesis in 92% isolated yield via addition of 2 equiv. of Me₃SiCl to the N₂ precursor 1 (Scheme 1). A ¹H NMR spectrum in thf-d₈ is consistent with a plane of symmetry bisecting 5 given the observation of seven paramagnetically shifted and broadened resonances (Fig. S3, ESI†). A sc-XRD study on 5 shows the (^tBupyrr₂pyr)Fe core with a chloride ligand occupying the fourth coordination site and {K(18-crown-6)(thf)₂}⁺ in the unit cell but not interacting with the iron complex. The Fe–Cl bond length is 2.2914(5) Å, which is longer than the Fe–Cl bond length of 2.1883(9) Å in the neutral ferric congener [(^tBupyrr₂pyr)FeCl].¹¹ In the structure of 5 the ∠N_pyr–Fe–Cl angle is 135.34(3)° and the geometric index τ₄ value is 0.60, which makes this geometry best described as seesaw. A solution state magnetic moment of 5, determined by Evans method, is 5.4 μ_B and is consistent with an S = 2 system.

In the interest of investigating the electronic structures of these mononuclear formally Fe^II ate complexes (3 and 5), ⁵⁷Fe Mössbauer spectroscopy and DC SQUID magnetometry measurements were performed on complex 5 as a representative example of this new class of compounds (Fig. 2). ⁵⁷Fe Mössbauer spectroscopy of 5 at 77 K shows a quadrupole doublet with an isomer shift of δ = 0.82 mm s⁻¹, a quadrupole splitting of ΔE_Q = 1.02 mm s⁻¹, and a linewidth of Γ_FWHM = 0.32 mm s⁻¹. These values are consistent with an S = 2 Fe^II ion on the ^tBupyrr₂pyr ligand platform.^11,13,21 This spin state was further confirmed by a DC SQUID magnetometry study which showed a field-independent magnetic moment of 5.28 μ_B (averaged between two independently measured samples) at 300 K. Unfortunately, due to difficulties in scaling up the synthesis of 3, we were unable to collect reliable ⁵⁷Fe Mössbauer spectroscopy and DC SQUID magnetometry measurements on this complex in order to directly compare with 5. We can, however, be reasonably confident in our assignment of its oxidation and spin state as S = 2 Fe^II due to its solution state magnetic moment of 4.8 μ_B and similarities with 5 in its electronic absorption spectrum (Fig. S22 and S23, ESI†).

Fig. 2 (Top) Zero-field ⁵⁷Fe-Mössbauer spectrum of 5 (solid state, 77 K). Measured data were fit with parameters δ = 0.82 mm s⁻¹, ΔE_Q = 1.02 mm s⁻¹, and Γ_FWHM = 0.32 mm s⁻¹. (bottom) Temperature-dependent SQUID magnetization measurement of a powdered sample of 5 recorded from 2 to 300 K with an applied magnetic field of 1 T. Measured data were fit with parameters S = 2, TIP = 1023 × 10⁻⁶ emu, |D| = 12 cm⁻¹, E/D = 0.14, and g_av = 2.14.

When complex 5 is reduced with an excess of KC₈ and one equivalent of 18-C-6 under an N₂ atmosphere, a gradual color change from red to dark purple is observed. Filtering the solution after one hour of reaction time and crystallization out of a concentrated toluene solution yields small black crystals that were identified as complex 2 by ¹H NMR spectroscopy (Fig. S20, ESI†), thus completing a synthetic cycle of benzene activation and borylation involving the Fe⁰/Fe^II couple. Future work will involve attempts at rendering this system catalytic as well as expanding the substrate scope with the aim of site-selective C–H bond activation.

EZ synthesized the complexes, and wrote part of the manuscript. LP collected and analysed the Mössbauer and SQUID data. AK assisted with the synthesis of complexes. MRG solved and curated the crystal structures. KM and DJM provided funding and equipment for the project and helped compose the manuscript.

This work was supported by the U.S. Department of Energy, Office of Basic Energy Sciences (DOE-BES-DESC0023340) and the University of Pennsylvania (UPenn, D. J. M.), the Friedrich-Alexander-Universität Erlangen – Nürnberg, and the Alexander von Humboldt Foundation (K. M. and D. J. M.). A. K. thanks the Vagelos Integrated Program in Energy Research at UPenn for support.

Data availability

Data for this article including full synthetic procedures and characterization are available in the ESI.†

Conflicts of interest

There are no conflicts to declare.

References

1. (a) S. K. Bose, L. Mao, L. Kuehn, U. Radius, J. Nekvinda, W. L. Santos, S. A. Westcott, P. G. Steel and T. B. Marder, Chem. Rev., 2021, 121, 13238–13341; (b) I. F. Yu, J. W. Wilson and J. F. Hartwig, Chem. Rev., 2023, 123, 11619–11663; (c) R. Arevalo and P. J. Chirik, J. Am. Chem. Soc., 2019, 141, 9106–9123.
2. (a) M. Lersch and M. Tilset, Chem. Rev., 2005, 105, 2471–2526; (b) J. A. Labinger and J. E. Bercaw, Nature, 2002, 417, 507–514; (c) B. A. Arndtsen, R. G. Bergman, T. A. Mobley and T. H. Peterson, Acc. Chem. Res., 1995, 28, 154–162; (d) A. E. Shilov and G. B. Shul’pin, Chem. Rev., 1997, 97, 2879–2932; (e) R. H. Crabtree, J. Chem. Soc., Dalton Trans., 2001, 2437–2450.
3. (a) K. C. Nicolaou, P. G. Bulger and D. Sarlah, Angew. Chem., Int. Ed., 2005, 44, 4442–4489; (b) J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508–524; (c) X. Chen, K. M. Engle, D. H. Wang and Y. Jin-Quan, Angew. Chem., Int. Ed., 2009, 48, 5094–5115.
4. N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457–2483.
5. (a) S. Camadanli, R. Beck, U. Flörke and H.-F. Klein, Organometallics, 2009, 28, 2300–2310; (b) M. V. Baker and L. D. Field, J. Am. Chem. Soc., 1987, 109, 2825–2826; (c) L. D. Field, R. W. Guest and P. Turner, Inorg. Chem., 2010, 49, 9086–9093; (d) S. Camadanli, R. Beck, U. Flörke and H.-F. Klein, Organometallics, 2009, 28, 2300–2310; (e) A. Casitas, H. Krause, S. Lutz, R. Goddard, E. Bill and A. Fürstner, Organometallics, 2018, 37, 729–739; (f) S. D. Ittel, C. A. Tolman, A. D. English and J. P. Jesson, J. Am. Chem. Soc., 1976, 98, 6073–6075; (g) S. F. McWilliams, D. L. J. Broere, C. J. V. Halliday, S. M. Bhutto, B. Q. Mercado and P. L. Holland, Nature, 2020, 584, 221–226; (h) W. D. Jones, G. P. Foster and J. M. Putinas, J. Am. Chem. Soc., 1987, 109, 5047–5048; (i) M. K. Whittlesey, R. J. Mawby, R. Osman, R. N. Perutz, L. D. Field, M. P. Wilkinson and M. W. George, J. Am. Chem. Soc., 1993, 115, 8627–8637; (j) C. A. Tolman, S. D. Ittel, A. D. English and J. P. Jesson, J. Am. Chem. Soc., 1979, 101, 1742–1751; (k) A. K. Hickey, S. A. Lutz, C.-H. Chen and J. M. Smith, Chem. Commun., 2017, 53, 1245–1248.
6. ed. W. M. Haynes, D. R. Lide and T. J. Bruno, CRC Press, Boca Raton, FL, 97th edn, 2016, p. 19.
7. (a) K. M. Waltz, X. He, C. Muhoro and J. F. Hartwig, J. Am. Chem. Soc., 1995, 117, 11357–11358; (b) T. J. Mazzacano and N. P. Mankad, Chem. Commun., 2015, 51, 5379–5382; (c) K. M. Waltz, C. N. Muhoro and J. F. Hartwig, Organometallics, 1999, 18, 3383–3393.
8. (a) L. Britton, J. H. Docherty, G. S. Nichol, A. P. Dominey and S. P. Thomas, Chin. J. Chem., 2022, 40, 2875–2881; (b) T. Dombray, C. G. Werncke, S. Jiang, M. Grellier, L. Vendier, S. Bontemps, J.-B. Sortais, S. Sabo-Etienne and C. Darcel, J. Am. Chem. Soc., 2015, 137, 4062–4065; (c) M. Kamitani, H. Kusaka and H. Yuge, Chem. Lett., 2019, 48, 898–901; (d) J.-L. Tu, A.-M. Hu, L. Guo and W. Xia, J. Am. Chem. Soc., 2023, 145, 7600–7611; (e) T. J. Mazzacano and N. P. Mankad, J. Am. Chem. Soc., 2013, 135, 17258–17261; (f) G. Yan, Y. Jiang, C. Kuang, S. Wang, H. Liu, Y. Zhang and J. Wang, Chem. Commun., 2010, 46, 3170–3172; (g) T. Kato, S. Kuriyama, K. Nakajima and Y. Nishibayashi, Chem. – Asian J., 2019, 14, 2097–2101; (h) H. Lee, T. He and S. P. Cook, Org. Lett., 2023, 25, 1–4; (i) M. Kamitani, Chem. Commun., 2021, 57, 13246–13258; (j) T. Hatanaka, Y. Ohki and K. Tatsumi, Chem. – Asian J., 2010, 5, 1657–1666.
9. (a) J. V. Obligacion, S. P. Semproni, I. Pappas and P. J. Chirik, J. Am. Chem. Soc., 2016, 138, 10645–10653; (b) J. V. Obligacion, S. P. Semproni and P. J. Chirik, J. Am. Chem. Soc., 2014, 136, 4133–4136; (c) T. P. Pabst and P. J. Chirik, J. Am. Chem. Soc., 2022, 144, 6465–6474.
10. S. R. Parmelee, T. J. Mazzacano, Y. Zhu, N. P. Mankad and J. A. Keith, ACS Catal., 2015, 5, 3689–3699.
11. K. Searles, S. Fortier, M. M. Khusniyarov, P. J. Carroll, J. Sutter, K. Meyer, D. J. Mindiola and K. G. Caulton, Angew. Chem., Int. Ed., 2014, 53, 14139–14143.
12. D. Sorsche, M. E. Miehlich, K. Searles, G. Gouget, E. M. Zolnhofer, S. Fortier, C.-H. Chen, M. Gau, P. J. Carroll, C. B. Murray, K. G. Caulton, M. M. Khusniyarov, K. Meyer and D. J. Mindiola, J. Am. Chem. Soc., 2020, 142, 8147–8159.
13. E. Zars, L. Gravogl, M. R. Gau, P. J. Carroll, K. Meyer and D. J. Mindiola, Chem. Sci., 2023, 14, 6770–6779.
14. (a) N. Hazari, Chem. Soc. Rev., 2010, 39, 4044–4056; (b) P. L. Holland, Dalton Trans., 2010, 39, 5415–5425.
15. J. B. Geri, J. P. Shanahan and N. K. Szymczak, J. Am. Chem. Soc., 2017, 139, 5952–5956.
16. S. Pietsch, E. C. Neeve, D. C. Apperley, R. Bertermann, F. Mo, D. Qiu, M. S. Cheung, L. Dang, J. Wang, U. Radius, Z. Lin, C. Kleeberg and T. B. Marder, Chem. – Eur. J., 2015, 21, 7082–7098.
17. J. D. Satterlee, Concepts Magn. Reson., 1990, 2, 69–79.
18. (a) T. R. Dugan, X. Sun, E. V. Rybak-Akimova, O. Olatunji-Ojo, T. R. Cundari and P. L. Holland, J. Am. Chem. Soc., 2011, 133, 12418–12421; (b) T. R. Dugan, J. M. Goldberg, W. W. Brennessel and P. L. Holland, Organometallics, 2012, 31, 1349–1360.
19. (a) N. Toriumi, K. Yamashita and N. Iwasawa, Chem. – Eur. J., 2021, 27, 12635–12641; (b) Q. K. Kang, Y. Lin, Y. Li, L. Xu, K. Li and H. Shi, Angew. Chem., Int. Ed., 2021, 60, 20391–20399; (c) Y. Nakamura, N. Yoshikai, L. Ilies and E. Nakamura, Org. Lett., 2012, 14, 3316–3319; (d) Q.-K. Kang, Y. Lin, Y. Li, L. Xu, K. Li and H. Shi, Angew. Chem., Int. Ed., 2021, 60, 20391–20399; (e) D. Guijarro and M. Yus, Tetrahedron, 2000, 56, 1135–1138.
20. D.-G. Yu and Z.-J. Shi, Angew. Chem., Int. Ed., 2011, 50, 7097–7100.
21. (a) E. Zars, L. Gravogl, M. Gau, P. J. Carroll, K. Meyer and D. J. Mindiola, Inorg. Chem., 2022, 61, 1079–1090; (b) D. Sorsche, M. E. Miehlich, E. M. Zolnhofer, P. J. Carroll, K. Meyer and D. J. Mindiola, Inorg. Chem., 2018, 57, 11552–11559.

---

Footnote

† Electronic supplementary information (ESI) available: ESI contains complete experimental details and spectral data. CCDC 2377358–2377361. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d4cc04127e

---