Metal-free photoinduced C(sp3)–H borylation of alkanes


Boronic acids and their derivatives are some of the most useful reagents in the chemical sciences1, with applications spanning pharmaceuticals, agrochemicals and functional materials. Catalytic C–H borylation is a powerful method for introducing these and other boron groups into organic molecules because it can be used to directly functionalize C–H bonds of feedstock chemicals without the need for substrate pre-activation1,2,3. These reactions have traditionally relied on precious-metal catalysts for C–H bond cleavage and, as a result, display high selectivity for borylation of aromatic C(sp2)–H bonds over aliphatic C(sp3)–H bonds4. Here we report a mechanistically distinct, metal-free borylation using hydrogen atom transfer catalysis5, in which homolytic cleavage of C(sp3)–H bonds produces alkyl radicals that are borylated by direct reaction with a diboron reagent. The reaction proceeds by violet-light photoinduced electron transfer between an N-alkoxyphthalimide-based oxidant and a chloride hydrogen atom transfer catalyst. Unusually, stronger methyl C–H bonds are borylated preferentially over weaker secondary, tertiary and even benzylic C–H bonds. Mechanistic studies indicate that the high methyl selectivity is a result of the formation of a chlorine radical–boron ‘ate’ complex that selectively cleaves sterically unhindered C–H bonds. By using a photoinduced hydrogen atom transfer strategy, this metal-free C(sp3)–H borylation enables unreactive alkanes to be transformed into valuable organoboron reagents under mild conditions and with selectivities that contrast with those of established metal-catalysed protocols.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Catalytic C–H borylation reactions.
Fig. 2: Photoinduced C–H borylations of alkanes.
Fig. 3: Photoinduced C–H borylations of silanes.
Fig. 4: Mechanistic studies.

Data availability

Materials and methods, experimental procedures, characterization data, spectra and additional mechanistic discussions are available in the Supplementary Information.


  1. 1.

    Hall, D. G. (ed.) Boronic Acids: Preparation and Applications in Organic Synthesis Medicine and Materials (Wiley, 2011).

  2. 2.

    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).

    CAS  Article  Google Scholar 

  3. 3.

    Xu, L. et al. Recent advances in catalytic C–H borylation reactions. Tetrahedron 73, 7123–7157 (2017).

    CAS  Article  Google Scholar 

  4. 4.

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

    CAS  Article  Google Scholar 

  5. 5.

    Capaldo, L. & Ravelli, D. Hydrogen atom transfer (HAT): a versatile strategy for substrate activation in photocatalyzed organic synthesis. Eur. J. Org. Chem. 2017, 2056–2071 (2017).

    CAS  Article  Google Scholar 

  6. 6.

    Cho, J.-Y., Tse, M. K., Holmes, D., Maleczka, R. E., Jr & Smith, M. R., III. Remarkably selective iridium catalysts for the elaboration of aromatic C–H bonds. Science 295, 305–308 (2002).

    ADS  CAS  Article  Google Scholar 

  7. 7.

    Ishiyama, T. et al. Mild iridium-catalyzed borylation of arenes. High turnover numbers, room temperature reactions, and isolation of a potential intermediate. J. Am. Chem. Soc. 124, 390–391 (2002).

    CAS  Article  Google Scholar 

  8. 8.

    Shimada, S., Batsanov, A. S., Howard, J. A. K. & Marder, T. B. Formation of aryl- and benzylboronate esters by rhodium-catalyzed C–H bond functionalization with pinacolborane. Angew. Chem. Int. Ed. 40, 2168–2171 (2001).

    CAS  Article  Google Scholar 

  9. 9.

    Ishiyama, T., Ishida, K., Takagi, J. & Miyaura, N. Palladium-catalyzed benzylic C–H borylation of alkylbenzenes with bis(pinacolato)diboron or pinacolborane. Chem. Lett. 30, 1082–1083 (2001).

    Article  Google Scholar 

  10. 10.

    Liskey, C. W. & Hartwig, J. F. Iridium-catalyzed C−H borylation of cyclopropanes. J. Am. Chem. Soc. 135, 3375–3378 (2013).

    CAS  Article  Google Scholar 

  11. 11.

    Ohmura, T., Torigoe, T. & Suginome, M. Functionalization of tetraorganosilanes and permethyloligosilanes at a methyl group on silicon via iridium-catalyzed C(sp 3)−H borylation. Organometallics 32, 6170–6173 (2013).

    CAS  Article  Google Scholar 

  12. 12.

    Larsen, M. A., Wilson, C. V. & Hartwig, J. F. Iridium-catalyzed borylation of primary benzylic C−H bonds without a directing group: scope, mechanism, and origins of selectivity. J. Am. Chem. Soc. 137, 8633–8643 (2015).

    CAS  Article  Google Scholar 

  13. 13.

    Palmer, W. N., Obligacion, J. V., Pappas, I. & Chirik, P. J. Cobalt-catalyzed benzylic borylation: enabling polyborylation and functionalization of remote, unactivated C(sp 3)−H bonds. J. Am. Chem. Soc. 138, 766–769 (2016).

    CAS  Article  Google Scholar 

  14. 14.

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

    CAS  Article  Google Scholar 

  15. 15.

    Li, Q., Liskey, C. W. & Hartwig, J. F. Regioselective borylation of the C−H bonds in alkylamines and alkyl ethers. Observation and origin of high reactivity of primary C−H bonds beta to nitrogen and oxygen. J. Am. Chem. Soc. 136, 8755–8765 (2014).

    CAS  Article  Google Scholar 

  16. 16.

    Larsen, M. A., Cho, S. H. & Hartwig, J. Iridium-catalyzed, hydrosilyl-directed borylation of unactivated alkyl C−H bonds. J. Am. Chem. Soc. 138, 762–765 (2016).

    CAS  Article  Google Scholar 

  17. 17.

    He, J., Shao, Q., Wu, Q. & Yu, J.-Q. Pd(ii)-catalyzed enantioselective C(sp 3)−H borylation. J. Am. Chem. Soc. 139, 3344–3347 (2017).

    CAS  Article  Google Scholar 

  18. 18.

    Reyes, R. L., Iwai, T., Maeda, S. & Sawamura, M. Iridium-catalyzed asymmetric borylation of unactivated methylene C(sp 3)−H bonds. J. Am. Chem. Soc. 141, 6817–6821 (2019).

    CAS  Article  Google Scholar 

  19. 19.

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

    CAS  Article  Google Scholar 

  20. 20.

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

    ADS  CAS  Article  Google Scholar 

  21. 21.

    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).

    CAS  Article  Google Scholar 

  22. 22.

    Ohmura, T., Torigoe, T. & Suginome, M. Iridium-catalysed borylation of sterically hindered C(sp 3)–H bonds: remarkable rate acceleration by a catalytic amount of potassium tert-butoxide. Chem. Commun. 50, 6333–6336 (2014).

    CAS  Article  Google Scholar 

  23. 23.

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

    ADS  CAS  Article  Google Scholar 

  24. 24.

    Ciriano, M. V., Korth, H.-G., van Scheppingen, W. B. & Mulder, P. Thermal stability of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and related N-alkoxyamines. J. Am. Chem. Soc. 121, 6375–6381 (1999).

    CAS  Article  Google Scholar 

  25. 25.

    Blanksby, S. J. & Ellison, G. B. Bond dissociation energies of organic molecules. Acc. Chem. Res. 36, 255–263 (2003).

    CAS  Article  Google Scholar 

  26. 26.

    Prokofjevs, A. & Vedejs, E. N-directed aliphatic C–H borylation using borenium cation equivalents. J. Am. Chem. Soc. 133, 20056–20059 (2011).

    CAS  Article  Google Scholar 

  27. 27.

    Fawcett, A. et al. Photoinduced decarboxylative borylation of carboxylic acids. Science 357, 283–286 (2017).

    ADS  CAS  Article  Google Scholar 

  28. 28.

    Guo, J.-J., Hu, A. & Zuo, Z. Photocatalytic alkoxy radical-mediated transformations. Tetrahedr. Lett. 59, 2103–2111 (2018).

    CAS  Article  Google Scholar 

  29. 29.

    Kim, S., Lee, T. A. & Song, Y. Facile generation of alkoxy radicals from N-alkoxyphthalimides. Synlett 1998, 471–472 (1998).

    Article  Google Scholar 

  30. 30.

    Zhang, J., Li, Y., Zhang, F., Hu, C. & Chen, Y. Generation of alkoxyl radicals by photoredox catalysis enables selective C(sp 3)–H functionalization under mild reaction conditions. Angew. Chem. Int. Ed. 55, 1872–1875 (2016).

    CAS  Article  Google Scholar 

  31. 31.

    Cheng, Y., Mück-Lichtenfeld, C. & Studer, A. Transition metal-free 1,2-carboboration of unactivated alkenes. J. Am. Chem. Soc. 140, 6221–6225 (2018).

    CAS  Article  Google Scholar 

  32. 32.

    Hu, A., Guo, J.-J., Pan, H. & Zuo, Z. Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis. Science 361, 668–672 (2018).

    ADS  CAS  Article  Google Scholar 

  33. 33.

    Qiao, Y., Yang, Q. & Schelter, E. J. Photoinduced Miyaura borylation by a rare-earth-metal photoreductant: the hexachlorocerate(iii) anion. Angew. Chem. Int. Ed. 57, 10999–11003 (2018).

    CAS  Article  Google Scholar 

  34. 34.

    Baban, J. A., Goodchild, N. J. & Roberts, B. P. Electron spin resonance studies of radicals derived from 1,3,2-benzodioxaboroles. J. Chem. Soc. Perkin Trans. 2 1986, 157–161 (1986).

    Article  Google Scholar 

  35. 35.

    Nunes, P. M. et al. C–H bond dissociation enthalpies in norbornane. An experimental and computational study. Org. Lett. 10, 1613–1616 (2008).

    CAS  Article  Google Scholar 

  36. 36.

    Sandfort, F., Strieth-Kalthoff, F., Klauck, F. J. R., James, M. J. & Glorius, F. Deaminative borylation of aliphatic amines enabled by visible light excitation of an electron donor–acceptor complex. Chem. Eur. J. 24, 17210–17214 (2018).

    CAS  Article  Google Scholar 

  37. 37.

    Tedder, J. M. Which factors determine the reactivity and regioselectivity of free radical substitution and addition reactions? Angew. Chem. Int. Edn Engl. 21, 401–410 (1982).

    Article  Google Scholar 

  38. 38.

    Carestia, A. M., Ravelli, D. & Alexanian, E. J. Reagent-dictated site selectivity in intermolecular aliphatic C–H functionalizations using nitrogen-centered radicals. Chem. Sci. 9, 5360–5365 (2018).

    CAS  Article  Google Scholar 

Download references


We thank the EPSRC (EP/R004978/1) for funding. We gratefully acknowledge A. Sedikides and A. Lennox (University of Bristol) for performing cyclic voltammetry experiments.

Author information




A.N. and V.K.A. conceived the project, directed the research and prepared the manuscript; C.S. performed the experimental work; all authors analysed the results.

Corresponding authors

Correspondence to Adam Noble or Varinder K. Aggarwal.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature thanks the anonymous reviewers for their contribution to the peer review of this work. Peer reviewer reports are available.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Figures 1-39, Supplementary Tables 1-21, Spectral Data and Supplementary References.

Peer Review File

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing