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Photoelectrochemically driven iron-catalysed C(sp3)−H borylation of alkanes

Nature Synthesis volume 3, pages 537–544 (2024)Cite this article

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Abstract

The development of strategies to access boronate esters from ubiquitous aliphatic C−H bonds is of long-standing interest in the synthesis community. Here photoelectrochemically driven C(sp3)−H borylation of alkanes is developed, in which iron, an abundant earth-based resource, is employed as a photoelectrochemical catalyst. Using this protocol, direct borylation of strong alkyl C−H bonds is efficiently achieved at a low oxidation potential of ∼0.3 V and mild conditions. A wide range of structurally diverse alkyl boronic esters, including versatile α-silyl boronic esters, can be accessed with good regioselectivity.

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Fig. 1: Introduction for C(sp3)−H borylation of alkanes.
Fig. 2: Substrate scope for C(sp3)−H bond borylation.
Fig. 3: Substrate scope for simple C(sp3)−H bond borylation of silanes.
Fig. 4: Gram-scale experiment and C(sp3)−H borylation of methane.
Fig. 5: Radical trapping experiments.
Fig. 6: Mechanistic studies.
Fig. 7: Control experiments and proposed mechanism.

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Data availability

Data relating to the characterization data of materials and products, general methods, optimization studies, experimental procedures, mechanistic studies and NMR spectra are available in the Supplementary Information. All data are also available from the corresponding author upon request.

References

  1. Jana, R., Pathak, T. P. & Sigman, M. S. Advances in transition metal (Pd,Ni,Fe)-catalyzed cross-coupling reactions using alkyl-organometallics as reaction partners. Chem. Rev. 111, 1417–1492 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fyfe, J. W. B. & Watson, A. J. B. Recent developments in organoboron chemistry: old dogs, new tricks. Chem 3, 31–55 (2017).

    Article  CAS  Google Scholar 

  3. Dunfaa, S., Lua, W., Chungua, X. & Chaoa, L. Recent advances in visible-light-promoted transformation of alkyl boron compounds. Chin. J. Org. Chem. 40, 3605–3619 (2020).

    Article  Google Scholar 

  4. Mkhalid, I. A. I., Barnard, J. H., Marder, T. B., Murphy, J. M. & Hartwig, J. F. C−H activation for the construction of C−B bonds. Chem. Rev. 110, 890–931 (2010).

    Article  CAS  PubMed  Google Scholar 

  5. Ros, A., Fernández, R. & Lassaletta, J. M. Functional group directed C–H borylation. Chem. Soc. Rev. 43, 3229–3243 (2014).

    Article  CAS  PubMed  Google Scholar 

  6. Bisht, R. et al. Metal-catalysed C–H bond activation and borylation. Chem. Soc. Rev. 51, 5042–5100 (2022).

    Article  CAS  PubMed  Google Scholar 

  7. Hartwig, J. F. Regioselectivity of the borylation of alkanes and arenes. Chem. Soc. Rev. 40, 1992–2002 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Hu, J., Lv, J. & Shi, Z. Emerging trends in C(sp3)–H borylation. Trends Chem. 4, 685–698 (2022).

    Article  CAS  Google Scholar 

  9. Chen, H. & Hartwig, J. F. Catalytic, regiospecific end-functionalization of alkanes: rhenium-catalyzed borylation under photochemical conditions. Angew. Chem. Int. Ed. 38, 3391–3393 (1999).

    Article  CAS  Google Scholar 

  10. Chen, H., Schlecht, S., Semple, T. C. & Hartwig, J. F. Thermal, catalytic, regiospecific functionalization of alkanes. Science 287, 1995–1997 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Lawrence, J. D., Takahashi, M., Bae, C. & Hartwig, J. F. Regiospecific functionalization of methyl C−H bonds of alkyl groups in reagents with heteroatom functionality. J. Am. Chem. Soc. 126, 15334–15335 (2004).

    Article  CAS  PubMed  Google Scholar 

  12. Hartwig, J. F. et al. Rhodium boryl complexes in the catalytic, terminal functionalization of alkanes. J. Am. Chem. Soc. 127, 2538–2552 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Murphy, J. M., Lawrence, J. D., Kawamura, K., Incarvito, C. & Hartwig, J. F. Ruthenium-catalyzed regiospecific borylation of methyl C−H bonds. J. Am. Chem. Soc. 128, 13684–13685 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Jones, M. R., Fast, C. D. & Schley, N. D. Iridium-Catalyzed sp3 C–H borylation in hydrocarbon solvent enabled by 2,2′-dipyridylarylmethane ligands. J. Am. Chem. Soc. 142, 6488–6492 (2020).

    Article  CAS  PubMed  Google Scholar 

  15. Oeschger, R. et al. Diverse functionalization of strong alkyl C–H bonds by undirected borylation. Science 368, 736–741 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cook, A. K., Schimler, S. D., Matzger, A. J. & Sanford, M. S. Catalyst-controlled selectivity in the C–H borylation of methane and ethane. Science 351, 1421–1424 (2016).

    Article  CAS  PubMed  Google Scholar 

  17. Smith, K. T. et al. Catalytic borylation of methane. Science 351, 1424–1427 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shu, C., Noble, A. & Aggarwal, V. K. Metal-free photoinduced C(sp3)–H borylation of alkanes. Nature 586, 714–719 (2020).

    Article  CAS  PubMed  Google Scholar 

  19. Horn, E. J., Rosen, B. R. & Baran, P. S. Synthetic organic electrochemistry: an enabling and innately sustainable method. J. Am. Chem. Soc. Cent. Sci. 2, 302–308 (2016).

    CAS  Google Scholar 

  20. Yan, M., Kawamata, Y. & Baran, P. S. Synthetic organic electrochemical methods since 2000: on the verge of a renaissance. Chem. Rev. 117, 13230–13319 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wiebe, A. et al. Electrifying organic synthesis. Angew. Chem. Int. Ed. 57, 5594–5619 (2018).

    Article  CAS  Google Scholar 

  22. Liu, J., Lu, L., Wood, D. & Lin, S. New redox strategies in organic synthesis by means of electrochemistry and photochemistry. J. Am. Chem. Soc. Cent. Sci. 6, 1317–1340 (2020).

    CAS  Google Scholar 

  23. Ma, C. et al. Recent advances in organic electrosynthesis employing transition metal complexes as electrocatalysts. Sci. Bull. 66, 2412–2429 (2021).

    Article  CAS  Google Scholar 

  24. Novaes, L. F. T. et al. Electrocatalysis as an enabling technology for organic synthesis. Chem. Soc. Rev. 50, 7941–8002 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhu, C., Ang, N. W. J., Meyer, T. H., Qiu, Y. & Ackermann, L. Organic electrochemistry: molecular syntheses with potential. J. Am. Chem. Soc. Cent. Sci. 7, 415–431 (2021).

    CAS  Google Scholar 

  26. Cheng, X. et al. Recent applications of homogeneous catalysis in electrochemical organic synthesis. CCS Chem. 4, 1120–1152 (2022).

    Article  CAS  Google Scholar 

  27. Kawamata, Y. et al. Scalable, electrochemical oxidation of unactivated C–H bonds. J. Am. Chem. Soc. 139, 7448–7451 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Francke, R. & Little, R. D. Redox catalysis in organic electrosynthesis: basic principles and recent developments. Chem. Soc. Rev. 43, 2492–2521 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Yu, Y., Guo, P., Zhong, J.-S., Yuan, Y. & Ye, K.-Y. Merging photochemistry with electrochemistry in organic synthesis. Org. Chem. Front. 7, 131–135 (2020).

    Article  Google Scholar 

  30. Huang, H., Steiniger, K. A. & Lambert, T. H. Electrophotocatalysis: combining light and electricity to catalyze reactions. J. Am. Chem. Soc. 144, 12567–12583 (2022).

    Article  CAS  PubMed  Google Scholar 

  31. Wu, S., Kaur, J., Karl, T. A., Tian, X. & Barham, J. P. Synthetic molecular photoelectrochemistry: new frontiers in synthetic applications, mechanistic insights and scalability. Angew. Chem. Int. Ed. 61, e202107811 (2022).

    Article  CAS  Google Scholar 

  32. Xu, P., Chen, P.-Y. & Xu, H.-C. Scalable photoelectrochemical dehydrogenative cross-coupling of heteroarenes with aliphatic C−H bonds. Angew. Chem. Int. Ed. 59, 14275–14280 (2020).

    Article  CAS  Google Scholar 

  33. Huang, H., Strater, Z. M. & Lambert, T. H. Electrophotocatalytic C–H functionalization of ethers with high regioselectivity. J. Am. Chem. Soc. 142, 1698–1703 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shen, T. & Lambert, T. H. Electrophotocatalytic diamination of vicinal C–H bonds. Science 371, 620–626 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shen, T. & Lambert, T. H. C–H amination via electrophotocatalytic Ritter-type reaction. J. Am. Chem. Soc. 143, 8597–8602 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shen, T., Li, Y.-L., Ye, K.-Y. & Lambert, T. H. Electrophotocatalytic oxygenation of multiple adjacent C–H bonds. Nature 614, 275–280 (2023).

    Article  CAS  PubMed  Google Scholar 

  37. Niu, L. et al. Manganese-catalyzed oxidative azidation of C(sp3)–H bonds under electrophotocatalytic conditions. J. Am. Chem. Soc. 142, 17693–17702 (2020).

    Article  CAS  PubMed  Google Scholar 

  38. Wang, F. & Stahl, S. S. Merging photochemistry with electrochemistry: functional-group tolerant electrochemical amination of C(sp3)−H Bonds. Angew. Chem. Int. Ed. 58, 6385–6390 (2019).

    Article  CAS  Google Scholar 

  39. Capaldo, L., Quadri, L. L., Merli, D. & Ravelli, D. Photoelectrochemical cross-dehydrogenative coupling of benzothiazoles with strong aliphatic C–H bonds. Chem. Commun. 57, 4424–4427 (2021).

    Article  CAS  Google Scholar 

  40. Liu, Y. et al. Time-resolved EPR revealed the formation, structure, and reactivity of N-centered radicals in an electrochemical C(sp3)–H arylation reaction. J. Am. Chem. Soc. 143, 20863–20872 (2021).

    Article  CAS  PubMed  Google Scholar 

  41. Cai, C.-Y. et al. Photoelectrochemical asymmetric catalysis enables site- and enantioselective cyanation of benzylic C–H bonds. Nat. Catal. 5, 943–951 (2022).

    Article  CAS  Google Scholar 

  42. Fan, W. et al. Electrophotocatalytic decoupled radical relay enables highly efficient and enantioselective benzylic C–H functionalization. J. Am. Chem. Soc. 144, 21674–21682 (2022).

    Article  CAS  PubMed  Google Scholar 

  43. Tan, Z., He, X., Xu, K. & Zeng, C. Electrophotocatalytic C−H functionalization of N-heteroarenes with unactivated alkanes under external oxidant-free conditions. ChemSusChem 15, e202102360 (2022).

  44. Zou, L., Wang, X., Xiang, S., Zheng, W. & Lu, Q. Paired oxidative and reductive catalysis: breaking the potential barrier of electrochemical C(sp3)−H alkenylation. Angew. Chem. Int. Ed. 62, e202301026 (2023).

    Article  CAS  Google Scholar 

  45. Corcé, V., Ollivier, C. & Fensterbank, L. Boron, silicon, nitrogen and sulfur-based contemporary precursors for the generation of alkyl radicals by single electron transfer and their synthetic utilization. Chem. Soc. Rev. 51, 1470–1510 (2022).

    Article  PubMed  Google Scholar 

  46. Juliá, F. Ligand-to-metal charge transfer (LMCT) photochemistry at 3d-metal complexes: an emerging tool for sustainable organic synthesis. ChemCatChem 14, e202200916 (2022).

    Article  Google Scholar 

  47. Abderrazak, Y., Bhattacharyya, A. & Reiser, O. Visible-light-induced homolysis of earth-abundant metal-substrate complexes: a complementary activation strategy in photoredox catalysis. Angew. Chem. Int. Ed. 60, 21100–21115 (2021).

    Article  CAS  Google Scholar 

  48. Chowdhury, R., Elek, G. Z., Meana-Baamonde, B. & Mendoza, A. Modular synthesis of (borylmethyl)silanes through orthogonal functionalization of a carbon atom. Org. Lett. 25, 1935–1940 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ohmura, T., Sasaki, I., Torigoe, T. & Suginome, M. A (borylmethyl)silane bearing three hydrolyzable groups on silicon: synthesis via iridium-catalyzed C(sp3)–H borylation and conversion to functionalized siloxanes. Organometallics 35, 1601–1603 (2016).

    Article  CAS  Google Scholar 

  50. Ohmura, T., Torigoe, T. & Suginome, M. Functionalization of tetraorganosilanes and permethyloligosilanes at a methyl group on silicon via iridium-catalyzed C(sp3)–H borylation. Organometallics 32, 6170–6173 (2013).

    Article  CAS  Google Scholar 

  51. Ohmura, T., Torigoe, T. & Suginome, M. Catalytic functionalization of methyl group on silicon: iridium-catalyzed C(sp3)–H Borylation of Methylchlorosilanes. J. Am. Chem. Soc. 134, 17416–17419 (2012).

    Article  CAS  PubMed  Google Scholar 

  52. Huang, B., Sun, Z. & Sun, G. Recent progress in cathodic reduction-enabled organic electrosynthesis: trends, challenges, and opportunities. eScience 2, 243–277 (2022).

    Article  Google Scholar 

  53. Bonet, A., Pubill-Ulldemolins, C., Bo, C., Gulyás, H. & Fernández, E. Transition-metal-free diboration reaction by activation of diboron compounds with simple Lewis bases. Angew. Chem. Int. Ed. 50, 7158–7161 (2011).

    Article  CAS  Google Scholar 

  54. Fu, N., Sauer, G. S. & Lin, S. Electrocatalytic radical dichlorination of alkenes with nucleophilic chlorine sources. J. Am. Chem. Soc. 139, 15548–15553 (2017).

    Article  CAS  PubMed  Google Scholar 

  55. Sang, R. et al. Copper-mediated dehydrogenative C(sp3)–H borylation of alkanes. J. Am. Chem. Soc. 145, 15207–15217 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sowndarya, S. V. S., St, John, P. C. & Paton, R. S. A quantitative metric for organic radical stability and persistence using thermodynamic and kinetic features. Chem. Sci. 12, 13158–13166 (2021).

    Article  Google Scholar 

  57. Manley, D. W. & Walton, J. C. A clean and selective radical homocoupling employing carboxylic acids with titania photoredox catalysis. Org. Lett. 16, 5394–5397 (2014).

    Article  CAS  PubMed  Google Scholar 

  58. Tu, J.-L., Hu, A.-M., Guo, L. & Xia, W. Iron-catalyzed C(sp3)–H borylation, thiolation, and sulfinylation enabled by photoinduced ligand-to-metal charge transfer. J. Am. Chem. Soc. 145, 7600–7611 (2023).

    Article  CAS  PubMed  Google Scholar 

  59. Liu, W. et al. Single-bond cleavage of alcohols. Org. Lett. 23, 8413–8418 (2021).

    Article  CAS  PubMed  Google Scholar 

  60. Dai, Z.-Y., Zhang, S.-Q., Hong, X., Wang, P.-S. & Gong, L.-Z. A practical FeCl3/HCl photocatalyst for versatile aliphatic C–H functionalization. Chem Catal. 2, 1211–1222 (2022).

    Article  CAS  Google Scholar 

  61. Wang, B. et al. Electrochemical borylation of alkyl halides: fast, scalable access to alkyl boronic esters. J. Am. Chem. Soc. 143, 12985–12991 (2021).

    Article  CAS  PubMed  Google Scholar 

  62. Zou, L., Xiang, S., Sun, R. & Lu, Q. Selective C(sp3)–H arylation/alkylation of alkanes enabled by paired electrocatalysis. Nat. Commun. 14, 7992 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhong, P.-F. et al. Photoelectrochemical oxidative C(sp3)−H borylation of unactivated hydrocarbons. Nat. Commun. 14, 6530 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work is financially supported by the National Natural Science Foundation of China (grant no. 22271227 for Q.L.) and Wuhan University.

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  1. The Institute for Advanced Studies (IAS), Wuhan University, Wuhan, P. R. China

    Yangmin Cao, Cheng Huang & Qingquan Lu

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  1. Yangmin Cao
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Contributions

Q.L. conceived and directed the project. Y.C. conducted most of the experimental studies. C.H. supported performance of synthetic experiments. Q.L. wrote the paper. All authors discussed the results, analysed the data and prepared the paper.

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Correspondence to Qingquan Lu.

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Nature Synthesis thanks Hai-Chao Xu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Peter Seavill, in collaboration with the Nature Synthesis team.

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Experimental details, Supplementary discussion, Figs. 1–30 and Tables 1–6.

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Cao, Y., Huang, C. & Lu, Q. Photoelectrochemically driven iron-catalysed C(sp3)−H borylation of alkanes. Nat. Synth 3, 537–544 (2024). https://doi.org/10.1038/s44160-023-00480-7

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