Hartwig-Miyaura C-H Borylation

Hartwig-Miyaura C-H Borylation

Overall Score4.5
  • Generality
  • Reagent Availability
  • Experimental User Friendliness
  • General Characteristics

Iridium catalysts coordinated with electron-donating bidentate ligands promote direct C-H borylation of non-halogenated aromatic rings. Organoboronate compounds are, of course, valuable as reagents of various chemical transformations.

The regioselectivity of the C-H borylation is highly sensitive to steric properties of the substituents on the aromatic ring. Therefore, meta-selective functionalization is possible unlike directed ortho-metallations and the Friedel-Crafts type reactions.

See the Miyaura-Ishiyama borylation for the conditions in which halogenated aromatic substrates are borylated.

  • General References

  • Cho, J. Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E., Jr.; Smith, M. R. Science 2002, 295, 305. DOI:10.1126/science.1067074
  • Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 390. DOI: 10.1021/ja0173019
  • Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. Angew. Chem. Int. Ed. 2002, 41, 3056. [abstract]
  • Ishiyama, T.; Nobuta, Y.; Hartwig, J. F.; Miyaura, N. Chem. Commun. 2003, 2924. DOI: 10.1039/B311103B


  • Reaction Mechanism

The fac-tris(boryl)iridium(III) complex generated from the iridium precursor, the ligand, and the diboron reagent is considered as the active catalytic species. The C-H activation of the aromatic ring by oxidative addition occurs at the empty coordination site after dissociation of the olefin ligand. (Ref: J. Am. Chem. Soc. 1993, 115, 9329; J. Am. Chem. Soc. 2003, 125, 16114; J. Am. Chem. Soc. 2005, 127, 14263)


  • Examples

The C-H borylation is influenced most by the steric interactions. Ortho-borylation therefore tends to be slow. (The table is extracted from this webpage.)


Porphyrin can be borylated selectively at the β-position.[1]


C-H borylation as a key step in the total synthesis of complanadine A.[2]


Using hydrosilane as a directing group, the otherwise-difficult ortho-borylation can be done.[3]


The borylations of cyclopropanes[4] and other sp3 C-H bonds[5] have been made possible by recent advancements.


The catalytic system has been extended to the silyation of unactivated sp3 C-H bonds and the example shown below utilizes the neighboring hydroxyl group as a tether.[6] This is a new useful way to synthesize polyol compounds such as sugars, because the C-Si bonds can be converted into hydroxyl groups by the Tamao oxidation.[7]


An example of para-selective C-H borylation catalyzed by the iridium catalyst bearing a bulky diphosphine ligand.[8]


The rhodium-catalyzed terminal functionalization of unactivated alkanes.[9]


  • Experimental Procedure

  • Experimental Tips

  • References

  1. Hata, H.; Shinokubo, H.; Osuka, A. J. Am. Chem. Soc. 2005, 127, 8264. DOI: 10.1021/ja051073r
  2. Fischer, D.F.; Sarpong, R. J. Am. Chem. Soc. 2010132, 5926. DOI: 10.1021/ja101893b
  3. Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008130, 7534.DOI:10.1021/ja8015878
  4. Liskey, C. W.; Hartwig, J. F. J. Am. Chem. Soc. 2013135, 3375. DOI: 10.1021/ja400103p
  5. (a) Liskey, C. W.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 12422. DOI: 10.1021/ja305596v (b) Li, W.; Liskey, C. W.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 8755. DOI: 10.1021/ja503676d (c) Miyamura, S.; Araki, M.; Suzuki, T.; Yamaguchi, J.; Itami, K. Angew. Chem. Int. Ed.  2015, 54, 846. DOI: 10.1002/anie.201409186
  6. (a) Simmon, E. M.; Hartwig, J. F. Nature 2012483, 70. doi:10.1038/nature10785 (b) Li, B.; Driess, M.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 6586. DOI: 10.1021/ja5026479
  7. Frihed, T. G.; Heuckendorff, M.; Pedersen, C. M.; Bols, M. Angew. Chem. Int. Ed. 2012, 51, 12285. DOI: 10.1002/anie.201206880
  8. Saito, Y.; Segawa, Y.; Itami, K. J. Am. Chem. Soc. 2015137, 5193. DOI: 10.1021/jacs.5b02052
  9. Chen, H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science 2000, 287, 1995. doi:10.1126/science.287.5460.1995
  • Related Reactions

  • Related Books

  • External Links

, , , ,