Mild and highly regioselective synthesis of biaryl acids via Rh (I)-catalyzed cross-dehydrogenative coupling of benzoic acids using sodium chlorite as oxidant


A mild and efficient synthesis for the biaryl acids via rhodium-catalyzed cross-dehydrogenative coupling reaction has been developed. This novel protocol with sodium chlorite as an oxidant featured many advantages such as mild reaction conditions, high regioselectivity, tolerance of various functional groups, and good to excellent yields.

This is a preview of subscription content, access via your institution.


  1. 1.

    Surry D S, Buchwald S L. Diamine ligands in copper-catalyzed reactions. Chemical Science (Cambridge), 2010, 1(1): 13–31

    CAS  Article  Google Scholar 

  2. 2.

    Magano J, Dunetz J R. Large-scale applications of transition metalcatalyzed couplings for the synthesis of pharmaceuticals. Chemical Reviews, 2011, 111(3): 2177–2250

    CAS  Article  Google Scholar 

  3. 3.

    Seechurn C C J, Kitching M O, Colacot T J, Snieckus V. Palladiumcatalyzed cross-coupling: A historical contextual perspective to the 2010 Nobel Prize. Angewandte Chemie International Edition, 2012, 51(21): 506–5085

    Google Scholar 

  4. 4.

    Girard S A, Knauber T, Li C J. The cross-dehydrogenative coupling of C(sp3)-H bonds: A versatile strategy for C‒C bond formations. Angewandte Chemie International Edition, 2014, 53(1): 74–100

    CAS  Article  Google Scholar 

  5. 5.

    Li C J. Cross-dehydrogenative coupling (CDC): Exploring C-C bond formations beyond functional group transformations. Accounts of Chemical Research, 2009, 42(2): 335–344

    CAS  Article  Google Scholar 

  6. 6.

    Li Z, Bohle D S, Li C J. Cu-catalyzed cross-dehydrogenative coupling: A versatile strategy for C‒C bond formations via the oxidative activation of sp3 C‒H bonds. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103 (24): 8928–8933

    CAS  Article  Google Scholar 

  7. 7.

    Sarhan A A O, Bolm C. Iron(III) chloride in oxidative C–C coupling reactions. Chemical Society Reviews, 2009, 38(9): 2730–2744

    CAS  Article  Google Scholar 

  8. 8.

    Sun C L, Li B J, Shi Z J. Direct C‒H transformation via iron catalysis. Chemical Reviews, 2011, 111(3): 1293–1314

    CAS  Article  Google Scholar 

  9. 9.

    Yeung C S, Dong V M. Catalytic dehydrogenative cross-coupling: Forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds. Chemical Reviews, 2011, 111(3): 1215–1292

    CAS  Article  Google Scholar 

  10. 10.

    Liu C, Zhang H, Shi W, Lei A W. Bond formations between two nucleophiles: Transition metal catalyzed oxidative cross-coupling Reactions. Chemical Reviews, 2011, 111(3): 1780–1824

    CAS  Article  Google Scholar 

  11. 11.

    Shang X, Liu Z Q. Transition metal-catalyzed C(vinyl)‒C(vinyl) bond formation via double C(vinyl)‒H bond activation. Chemical Society Reviews, 2013, 42(8): 3253–3260

    CAS  Article  Google Scholar 

  12. 12.

    Liu C, Yuan J W, Gao M, Tang S, Li W, Shi R Y, Lei A W. Oxidative coupling between two hydrocarbons: An update of recent C‒H functionalizations. Chemical Reviews, 2015, 115(22): 12138–12204

    CAS  Article  Google Scholar 

  13. 13.

    Ashenhurst J A. Intermolecular oxidative cross-coupling of arenes. Chemical Society Reviews, 2010, 39(2): 540–548

    CAS  Article  Google Scholar 

  14. 14.

    Stuart D R, Fagnou K. The catalytic cross-coupling of unactivated arenes. Science, 2007, 316(5828): 1172–1175

    CAS  Article  Google Scholar 

  15. 15.

    Hull K L, Sanford M S. Catalytic and highly regioselective crosscoupling of aromatic C‒H substrates. Journal of the American Chemical Society, 2007, 129(39): 11904–11905

    CAS  Article  Google Scholar 

  16. 16.

    Stuart D R, Villemure E, Fagnou K. Elements of regiocontrol in palladium-catalyzed oxidative arene cross-coupling. Journal of the American Chemical Society, 2007, 129(40): 12072–12073

    CAS  Article  Google Scholar 

  17. 17.

    Zhang H B, Liu L, Chen Y J, Wang D, Li C J. “On water”-promoted direct coupling of indoles with 1,4-benzoquinones without catalyst. European Journal of Organic Chemistry, 2006, 2006(4): 869–873

    Article  Google Scholar 

  18. 18.

    Campbell A N, Meyer E B, Stahl S S. Regiocontrolled aerobic oxidative coupling of indoles and benzene using Pd catalysts with 4,5-diazafluorene Ligands. Chemical Communications (Cambridge), 2011, 47(37): 10257–10259

    CAS  Article  Google Scholar 

  19. 19.

    Cambeiro X C, Ahlsten N, Larrosa I. Au-catalyzed cross-coupling of arenes via double C–H activation. Journal of the American Chemical Society, 2015, 137(50): 15636–15639

    CAS  Article  Google Scholar 

  20. 20.

    Xu H, Shang M, Dai H X, Yu J Q. Ligand-controlled para-selective C–H arylation of monosubstituted arenes. Organic Le tters, 2015, 17 (15): 3830–3833

    CAS  Article  Google Scholar 

  21. 21.

    Wencel-Delord J, Nimphius C, Patureau FW, Glorius F. [RhIIICp*]-catalyzed dehydrogenative aryl-aryl bond formation. Angewandte Chemie International Edition, 2012, 51(9): 2247–2251

    CAS  Article  Google Scholar 

  22. 22.

    Kuhl N, Hopkinson M N, Glorius F. Selective rhodium(III)-catalyzed cross-dehydrogenative coupling of furan and thiophene derivatives. Angewandte Chemie International Edition, 2012, 51 (33): 8230–8234

    CAS  Article  Google Scholar 

  23. 23.

    Morimoto K, Itoh M, Hirano K, Satoh T, Shibata Y, Tanaka K, Miura M. Synthesis of fluorene derivatives through rhodiumcatalyzed dehydrogenative cyclization. Angewandte Chemie International Edition, 2012, 51(22): 5359–5362

    CAS  Article  Google Scholar 

  24. 24.

    Dong J, Long Z, Song F, We N, Guo Q, Lan J, You J. Rhodium or ruthenium-catalyzed oxidative C‒H/C‒H cross-coupling: Direct access to extended p-conjugated systems. Angewandte Chemie International Edition, 2013, 52(2): 580–584

    CAS  Article  Google Scholar 

  25. 25.

    Zhang T, Lin W. Metal-organic frameworks for artificial photosynthesis and photocatalysis. Chemical Society Reviews, 2014, 43 (16): 5982–5993

    CAS  Article  Google Scholar 

  26. 26.

    Li D S, Wu Y P, Zhao J, Zhang J, Lu J Y. Metal-organic frameworks based upon non-zeotype 4-connected topology. Coordination Chemistry Reviews, 2014, 261: 1–27

    CAS  Article  Google Scholar 

  27. 27.

    Zhang H X, Wang F, Yang H, Tan Y X, Zhang J, Bu X. Interrupted zeolite LTA and ATN-type boron imidazolate frameworks. Journal of the American Chemical Society, 2011, 133(31): 11884–11887

    CAS  Article  Google Scholar 

  28. 28.

    Zhang Y H, Li X, Song S. White light emission based on a single component Sm(III) framework and a two component Eu(III)-doped Gd(III) framework constructed from 2,2′-diphenyl dicarboxylate and 1H-imidazo[4,5-f][1,10]-phenanthroline. Chemical Communications, 2013, 49(88): 10397–10399

    CAS  Article  Google Scholar 

  29. 29.

    Guo S Q, Tian D, Luo Y H, Zhang H. Solvothermal synthesis, structure, and luminescence of a 3-D Cd(II) complex assembled with biphenyl-2,5,2′,5′-tetracarboxylic acid involving in situ ligand reaction. Journal of Coordination Chemistry, 2012, 65(2): 308–315

    CAS  Article  Google Scholar 

  30. 30.

    Jurd L. Plant polyphenols. III. The isolation of a new ellagitannin from the pellicle of the walnut. Journal of the American Chemical Society, 1958, 80(9): 2249–2252

    CAS  Article  Google Scholar 

  31. 31.

    Chen D F, Zhang S X, Xie L, Xie J X, Chen K, Kashiwada Y, Zhou B N, Wang P, Cosentino L M, Lee K H. Anti-aids agents—XXVI. Structure-activity correlations of Gomisin-G-related anti-HIV lignans from Kadsura interior and of related synthetic analogues. Bioorganic & Medicinal Chemistry, 1997, 5(8): 1715–1723

    CAS  Article  Google Scholar 

  32. 32.

    Nelson T D, Meyers A I. A rapid total synthesis of an ellagitannin. Journal of Organic Chemistry, 1994, 59(9): 2577–2580

    CAS  Article  Google Scholar 

  33. 33.

    Parida K N, Moorthy J N. Synthesis of o-carboxyarylacrylic acids by room temperature oxidative cleavage of hydroxynaphthalenes and higher aromatics with oxone. Journal of Organic Chemistry, 2015, 80(16): 8354–8360

    CAS  Article  Google Scholar 

  34. 34.

    Zhang D L, Zhou L Y, Quan JM, Zhang W, Gu L Q, Huang Z S, An L K. Oxygen insertion of o-quinone under catalytic hydrogenation conditions. Organic Letters, 2013, 15(6): 1162–1165

    CAS  Article  Google Scholar 

  35. 35.

    Kang S, Lee S, Jeon M S, Kim M, Kim Y S, Han H, Yang J W. In situ generation of hydroperoxide by oxidation of benzhydrols to benzophenones using sodium hydride under oxygen atmosphere: Use for the oxidative cleavage of cyclic 1,2-diketones to dicarboxylic acids. Tetrahedron Letters, 2013, 54(5): 373–376

    CAS  Article  Google Scholar 

  36. 36.

    Barati B, Moghadam M, Rahmati A, Tangestaninejad S, Mirkhani V, Mohammadpoor-Baltork I. Ruthenium hydride catalyzed direct oxidation of alcohols to carboxylic acids via transfer hydrogenation: Styrene oxide as oxygen source. Synlett, 2013, 24(1): 90–96

    CAS  Google Scholar 

  37. 37.

    Lin G Q, Hong R. A new reagent system for modified Ullmann-type coupling reactions: NiCl2(PPh3)2/PPh3/Zn/ NaH/toluene. Journal of Organic Chemistry, 2001, 66(8): 2877–2880

    CAS  Article  Google Scholar 

  38. 38.

    Ram R N, Singh V. Palladium(II) chloride/EDTA-catalyzed biaryl homo-coupling of aryl halides in aqueous medium in the presence of ascorbic acid. Tetrahedron Letters, 2006, 47(43): 7625–7628

    CAS  Article  Google Scholar 

  39. 39.

    Montoya-Pelaez P J, Uh Y S, Lata C, Thompson MP, Lemieux R P, Crudden C M. The synthesis and resolution of 2,2′-, 4,4′-, and 6,6′-substituted chiral biphenyl derivatives for application in the preparation of chiral materials. Journal of Organic Chemistry, 2006, 71(16): 5921–5929

    CAS  Article  Google Scholar 

  40. 40.

    Surry D S, Fox D J, Macdonald S J F, Spring D R. Aryl-aryl coupling via directed lithiation and oxidation. Chemical Communications (Cambridge), 2005, (20): 2589–2590

    Article  Google Scholar 

  41. 41.

    Gong H, Zeng H Y, Zhou F, Li C J. Rhodium(I)-catalyzed regiospecific dimerization of aromatic acids: Two direct C‒H bond activations in water. Angewandte Chemie International Edition, 2015, 54(19): 5718–5721

    CAS  Article  Google Scholar 

  42. 42.

    Song G Y, Wang WF, Li X W. C–C, C–O and C–N bond formation via rhodium-catalyzed oxidative C–H activation. Chemical Society Reviews, 2012, 41(9): 3651–3678

    CAS  Article  Google Scholar 

  43. 43.

    Colby D A, Bergman R G, Ellman J A. Rhodium-catalyzed C-C bond formation via heteroatom-directed C-H bond activation. Chemical Reviews, 2010, 110(2): 624–655

    CAS  Article  Google Scholar 

  44. 44.

    Stuart D R, Bertrand-Laperle M, Burgess K M N, Fagnou K. Indole synthesis via rhodium catalyzed oxidative coupling of acetanilides and internal alkynes. Journal of the American Chemical Society, 2008, 130(49): 16474–16475

    CAS  Article  Google Scholar 

  45. 45.

    Guimond N, Gouliaras C, Fagnou K. Rhodium(III)-catalyzed isoquinolone synthesis: The N-O bond as a handle for C-N bond formation and catalyst turnover. Journal of the American Chemical Society, 2010, 132(20): 6908–6909

    CAS  Article  Google Scholar 

  46. 46.

    Hyster T K, Rovis T. Rhodium-catalyzed oxidative cycloaddition of benzamides and alkynes via C‒H/N‒H activation. Journal of the American Chemical Society, 2010, 132(30): 10565–10569

    CAS  Article  Google Scholar 

  47. 47.

    Patureau F W, Besset T, Kuhl N, Glorius F. Diverse strategies toward indenol and fulvene derivatives: Rh-catalyzed C‒H activation of aryl ketones followed by coupling with internal alkynes. Journal of the American Chemical Society, 2011, 133(7): 2154–2156

    CAS  Article  Google Scholar 

  48. 48.

    Tan X, Liu B X, Li X Y, Li B, Xu S S, Song H B, Wang B Q. Rhodium-catalyzed cascade oxidative annulation leading to substituted naphtho[1,8-bc]pyrans by sequential cleavage of C(sp2)‒H/C(sp3)‒H and C(sp2)‒H/O‒H bonds. Journal of the American Chemical Society, 2012, 134(39): 16163–16166

    CAS  Article  Google Scholar 

Download references


We are grateful to the Canada Research Chair (Tier 1) foundation (to C.-J. L.), NSERC, CFI, and FQRNT (CCVC) for their support of our research.

Author information



Corresponding author

Correspondence to Chaojun Li.

Electronic supplementary material


Mild and Highly Regioselective Synthesis of Biaryl Acids via Rh(I)-Catalyzed Cross-Dehydrogenative Coupling of Benzoic Acids Using Sodium Chlorite as Oxidant

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Zhu, Y. & Li, C. Mild and highly regioselective synthesis of biaryl acids via Rh (I)-catalyzed cross-dehydrogenative coupling of benzoic acids using sodium chlorite as oxidant. Front. Chem. Sci. Eng. 12, 3–8 (2018).

Download citation


  • biaryl acids
  • cross-dehydrogenative coupling
  • rhodium-catalyzed