Science China Chemistry

, Volume 54, Issue 11, pp 1670–1687 | Cite as

Transition metal-catalyzed decarboxylative cross-coupling reactions

  • Rui Shang
  • Lei LiuEmail author
Reviews Special Topic · In Honor of the 80th Birthday of Professor Ronald Breslow


Transition metal-catalyzed decarboxylative cross-coupling reactions have recently emerged as a new and important category of organic transformations that find versatile applications in the construction of carbon-carbon and carbon-heteroatom bonds. The use of relatively cheap and stable carboxylic acids to replace organometallic reagents enables the decarboxylative cross-coupling reactions to proceed with good selectivities and functional group tolerance. In the present review we summarize the various types of decarboxylative cross-coupling reactions catalyzed by different transition metal complexes. The scope and applications of these reactions are described. The challenges and opportunities in the field are discussed.


decarboxylation cross-coupling reaction transition metal catalysis organic synthesis 


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  1. 1.
    De Meijere A, Diederich F. Metal-catalyzed Cross-Coupling Reactions. Weinheim: Wiley-VCH, 2004CrossRefGoogle Scholar
  2. 2.
    Bjorklund C, Nilsson M. Decarboxylative couplings of 2,6-dinitrobenzoic acids. Acta Chem Scand, 1968, 22: 2585–2588CrossRefGoogle Scholar
  3. 3.
    Nilsson M. A new biaryl synthesis illustrating a connection between the Ullmann biaryl synthesis and copper-catalyzed decarboxylation. Acta Chem Scand, 1966, 20: 423–426CrossRefGoogle Scholar
  4. 4.
    Cohen T, Schambach RA. The copper-quinoline decarboxylation. J Am Chem Soc, 1970, 92: 3189–3190CrossRefGoogle Scholar
  5. 5.
    Cairncross A, Roland JR, Henderson RM, Sheppard WA. Organocopper intermediates via decarboxylation of cuprous carboxylates. J Am Chem Soc, 1970, 92: 3187–3189CrossRefGoogle Scholar
  6. 6.
    Goossen LJ, Thiel WR, Rodriguez N, Linder C. Copper-catalyzed protodecarboxylation of aromatic carboxylic acids. Adv Synth Catal, 2007, 349: 2241–2246CrossRefGoogle Scholar
  7. 7.
    Goossen LJ, Manjolinho F, Khan B-A, Rodríguez N. Microwave-assisted Cu-catalyzed protodecarboxylation of aromatic carboxylic acids. J Org Chem, 2009, 74: 2620–2623CrossRefGoogle Scholar
  8. 8.
    Kolarovič A, Fáberová Z. Catalytic decarboxylation of 2-alkynoic acids. J Org Chem, 2009, 74: 7199–7202CrossRefGoogle Scholar
  9. 9.
    Gooßen LJ, Linder C, Rodríguez N, Lange PP, Fromm A. Silver-catalysed protodecarboxylation of carboxylic acids. Chem Commun, 2009, 7173–7175Google Scholar
  10. 10.
    Lu P, Sanchez C, Cornella J, Larrosa I. Silver-catalyzed protodecarboxylation of heteroaromatic carboxylic acids. Org Lett, 2009, 11: 5710–5713CrossRefGoogle Scholar
  11. 11.
    Goossen LJ, Rodríguez N, Linder C, Lange PP, Fromm A. Comparative study of copper- and silver-catalyzed protodecarboxylations of carboxylic acids. ChemCatChem, 2010, 2: 430–442CrossRefGoogle Scholar
  12. 12.
    Dupuy S, Lazreg F, Slawin A MZ, Cazin C SJ, Nolan S P. Decarboxylation of aromatic carboxylic acids by gold(I)-N-heterocyclic carbene (NHC) complexes. Chem Commun, 2011, 47: 5455–5457CrossRefGoogle Scholar
  13. 13.
    Cornella J, Rosillo-Lopez M, Larrosa I. A novel mode of reactivity for gold(I): The decarboxylative activation of (hetero)aromatic carboxylic acids. Adv Synth Catal, 2011, 353: 1359–1366CrossRefGoogle Scholar
  14. 14.
    Dickstein JS, Mulrooney CA, O’Brien EM, Morgan BJ, Kozlowski MC. Development of a catalytic aromatic decarboxylation reaction. Org Lett, 2007, 9: 2441–2444CrossRefGoogle Scholar
  15. 15.
    Tanaka D, Romeril SP, Myers AG. On the mechanism of the palladium(II)-catalyzed decarboxylative olefination of arene carboxylic acids. Crystallographic characterization of non-phosphine palladium( II) intermediates and observation of their stepwise transformation in Heck-like processes. J Am Chem Soc, 2005, 127: 10323–10333CrossRefGoogle Scholar
  16. 16.
    Sun ZM, Zhang J, Zhao P. Rh(I)-catalyzed decarboxylative transformations of arenecarboxylic acids: Ligand- and reagent-controlled selectivity toward hydrodecarboxylation or Heck-Mizoroki products. Org Lett, 2010, 12: 992–995CrossRefGoogle Scholar
  17. 17.
    Goossen LJ, Deng GJ, Levy LM. Synthesis of biaryls via catalytic decarboxylative coupling. Science, 2006, 313: 662–664CrossRefGoogle Scholar
  18. 18.
    Goossen LJ, Zimmermann B, Knauber T. Palladium/Copper-catalyzed decarboxylative cross-coupling of aryl chlorides with potassium carboxylates. Angew Chem Int Ed, 2008, 47: 7103–7106CrossRefGoogle Scholar
  19. 19.
    Goossen LJ, Rodríguez N, Linder C. Decarboxylative biaryl synthesis from aromatic carboxylates and aryl triflates. J Am Chem Soc, 2008, 130: 15248–15249CrossRefGoogle Scholar
  20. 20.
    Goossen LJ, Rodríguez N, Lange PP, Linder C. Decarboxylative cross-coupling of aryl tosylates with aromatic carboxylate salts. Angew Chem Int Ed, 2010, 49: 1111–1114CrossRefGoogle Scholar
  21. 21.
    Goossen LJ, Rodríguez N, Melzer B, Linder C, Deng GJ, Levy LM. Biaryl synthesis via Pd-catalyzed decarboxylative coupling of aromatic carboxylates with aryl halides. J Am Chem Soc, 2007, 129: 4824–4833CrossRefGoogle Scholar
  22. 22.
    Becht JM, Catala C, Drian CL, Wagner A. Synthesis of biaryls via decarboxylative Pd-catalyzed cross-coupling reaction. Org Lett, 2007, 9: 1781–1783CrossRefGoogle Scholar
  23. 23.
    Becht JM, Drian CL. Biaryl synthesis via decarboxylative Pdcatalyzed reactions of arenecarboxylic acids and diaryliodonium triflates. Org Lett, 2008, 10: 3161–3164CrossRefGoogle Scholar
  24. 24.
    Wang ZY, Ding QP, He XD, Wu J. Pd-catalyzed decarboxylative couplings of arenecarboxylic acids with aryl iodides. Tetrahedron, 2009, 65: 4635–4638CrossRefGoogle Scholar
  25. 25.
    Zhang F, Greaney MF. Decarboxylative cross-coupling of azoyl carboxylic acids with aryl halides. Org Lett, 2010, 12: 4745–4747CrossRefGoogle Scholar
  26. 26.
    Goossen LJ, Lange PP, Rodríguez N, Linder C. Low-temperature Ag/Pd-catalyzed decarboxylative cross-coupling of aryl triflates with aromatic carboxylate salts. Chem Eur J, 2010, 16: 3906–3909CrossRefGoogle Scholar
  27. 27.
    Peschko C, Winklhofer C, Steglich W. Biomimetic total synthesis of lamellarin l by coupling of two different arylpyruvic acid units. Chem Eur J, 2000, 6: 1147–1152CrossRefGoogle Scholar
  28. 28.
    Forgione P, Brochu MC, St-Onge M, Thesen KH, Bailey MD, Bilodeau F. Unexpected intermolecular Pd-catalyzed cross-coupling reaction employing heteroaromatic carboxylic acids as coupling partners. J Am Chem Soc, 2006, 128: 11350–11351CrossRefGoogle Scholar
  29. 29.
    Shang R, Xu Q, Jiang YY, Wang Y, Liu L. Pd-catalyzed decarboxylative cross coupling of potassium polyfluorobenzoates with aryl bromides, chlorides, and triflates. Org Lett, 2010, 12: 10001003CrossRefGoogle Scholar
  30. 30.
    Miyasaka M, Fukushima A, Satoh T, Hirano K, Miura M. Fluorescent diarylindoles by palladium-catalyzed direct and decarboxylative arylations of carboxyindoles. Chem Eur J, 2009, 15: 3674–3677CrossRefGoogle Scholar
  31. 31.
    Arroyave FA, Reynolds JR. 3,4-Propylenedioxypyrrole-based conjugated oligomers via Pd-mediated decarboxylative cross coupling. Org Lett, 2010, 12: 1328–1331CrossRefGoogle Scholar
  32. 32.
    Shang R, Fu Y, Wang Y, Xu Q, Yu HZ, Liu L. Copper-catalyzed decarboxylative cross-coupling of potassium polyfluorobenzoates with aryl iodides and bromides. Angew Chem Int Ed, 2009, 48: 9350–9354CrossRefGoogle Scholar
  33. 33.
    Moon J, Jeong M, Nam H, Ju J, Moon JH, Jung HM, Lee S. One-pot synthesis of diarylalkynes using palladium-catalyzed Sonogashira reaction and decarboxylative coupling of sp carbon and sp2 carbon. Org Lett, 2008, 10: 945–948CrossRefGoogle Scholar
  34. 34.
    Zhang WW, Zhang XG, Li JH. Palladium-catalyzed decarboxylative coupling of alkynyl carboxylic acids with benzyl halides or aryl halides. J Org Chem, 2010, 75: 5259–5264CrossRefGoogle Scholar
  35. 35.
    Zhao DB, Gao C, Su XY, He YQ, You JS, Xue Y. Copper-catalyzed decarboxylative cross-coupling of alkynyl carboxylic acids with aryl halides. Chem Commun, 2010, 46: 9049–9051CrossRefGoogle Scholar
  36. 36.
    Goossen LJ, Rudolphi F, Oppel C, Rodríguez N. Synthesis of ketones from α-oxocarboxylates and aryl bromides by Cu/Pd-catalyzed decarboxylative cross-coupling. Angew Chem Int Ed, 2008, 47: 3043–3045CrossRefGoogle Scholar
  37. 37.
    Shang R, Fu Y, Li JB, Zhang SL, Guo QX, Liu L. Synthesis of aromatic esters via Pd-catalyzed decarboxylative coupling of potassium oxalate monoesters with aryl bromides and chlorides. J Am Chem Soc, 2009, 131: 5738–5739CrossRefGoogle Scholar
  38. 38.
    Shang R, Yang ZW, Wang Y, Zhang SL, Liu L. Palladium-catalyzed decarboxylative couplings of 2-(2-azaaryl)acetates with aryl halides and triflates. J Am Chem Soc, 2010, 132: 14391–14393CrossRefGoogle Scholar
  39. 39.
    Shang R, Ji DS, Chu L, Fu Y, Liu L. Synthesis of α-aryl nitriles through palladium-catalyzed decarboxylative coupling of cyanoacetate salts with aryl halides and triflates. Angew Chem Int Ed, 2011, 50: 4470–4474CrossRefGoogle Scholar
  40. 40.
    Yeung PY, Chung KH, Kwong FY. Palladium-catalyzed decarboxylative arylation of potassium cyanoacetate: Synthesis of α-diaryl nitriles from aryl halides. Org Lett, 2011, 13: 2912–2915CrossRefGoogle Scholar
  41. 41.
    Shang R, Huang Z, Chu L, Fu Y, Liu L. Palladium-catalyzed decarboxylative coupling of potassium nitrophenyl acetates with aryl halides. Org Lett, 2011, 13: 4240–4243CrossRefGoogle Scholar
  42. 42.
    Yamashita M, Hirano K, Satoh T, Miura M. Synthesis of α,ω-diarylbutadienes and-hexatrienes via decarboxylative coupling of cinnamic acids with vinyl bromides under palladium catalysis. Org Lett, 2010, 12: 592–595CrossRefGoogle Scholar
  43. 43.
    Wang Z, Ding Q, He X, Wu J. Palladium-catalyzed decarboxylative cross-coupling reaction of cinnamic acid with aryl iodide. Org Biomol Chem, 2009, 7: 863–865CrossRefGoogle Scholar
  44. 44.
    Wang JT, Cui ZL, Zhang YX, Li HJ, Wu LM, Liu ZQ. Pd(II)-catalyzed decarboxylative allylation and Heck-coupling of arene carboxylates with allylic halides and esters. Org Biomol Chem, 2011, 9: 663–666CrossRefGoogle Scholar
  45. 45.
    Myers AG, Tanaka D, Mannion MR. Development of a decarboxylative palladation reaction and its use in a Heck-type olefination of arene carboxylates. J Am Chem Soc, 2002, 124: 11250–11251CrossRefGoogle Scholar
  46. 46.
    Zhang SL, Fu Y, Shang R, Guo QX, Liu L. Theoretical analysis of factors controlling Pd-catalyzed decarboxylative coupling of carboxylic acids with olefins. J Am Chem Soc, 2010, 132: 638–646CrossRefGoogle Scholar
  47. 47.
    Hu P, Kan J, Su W, Hong M. Pd(O2CCF3)2/benzoquinone: A versatile catalyst system for the decarboxylative olefination of arene carboxylic acids. Org Lett, 2009, 11: 2341–2344CrossRefGoogle Scholar
  48. 48.
    Fu Z, Huang S, Su W, Hong M. Pd-catalyzed dearboxylative Heck coupling with dioxygen as the terminal oxidant. Org Lett, 2010, 12: 4992–4995CrossRefGoogle Scholar
  49. 49.
    Voutchkova A, Coplin A, Leadbeater N-E, Crabtree R-H. Palladium-catalyzed decarboxylative coupling of aromatic acids with aryl halides or unactivated arenes using microwave heating. Chem Commun, 2008, 6312-6314Google Scholar
  50. 50.
    Wang CY, Piel I, Glorius F. Palladium-catalyzed intramolecular direct arylation of benzoic acids by tandem decarboxylation/C-H activation. J Am Chem Soc, 2009, 131: 4194–4195CrossRefGoogle Scholar
  51. 51.
    Zhou J, Hu P, Zhang M, Huang SJ, Wang M, Su WP. Aversatile catalyst for intermolecular direct arylation of indoles with benzoic acids as arylating reagents. Chem Eur J, 2010, 16: 5876–5881Google Scholar
  52. 52.
    Cornella J, Lu P, Larrosa I. Intermolecular decarboxylative direct C-3 arylation of indoles with benzoic acids. Org Lett, 2009, 11: 5506–5509CrossRefGoogle Scholar
  53. 53.
    Fang P, Li MZ, Ge HB. Room temperature palladium-catalyzed decarboxylative ortho-acylation of acetanilides with α-oxocarboxylic acids. J Am Chem Soc, 2010, 132: 11898–11899CrossRefGoogle Scholar
  54. 54.
    Li M, Ge H. Decarboxylative acylation of arenes with α- oxocarboxylic acids via palladium-catalyzed C-H activation. Org Lett, 2010, 12: 3464–3467CrossRefGoogle Scholar
  55. 55.
    Zhang FZ, Greaney MF. Decarboxylative C-H cross-coupling of azoles. Angew Chem Int Ed, 2010, 49: 2768–2771Google Scholar
  56. 56.
    Xie K, Yang Z, Zhou X, Li X, Wang S, Tan Z, An X, Guo CC. Pd-catalyzed decarboxylative arylation of thiazole, benzoxazole, and polyfluorobenzene with substituted benzoic acids. Org Lett, 2010, 12: 1564–1567CrossRefGoogle Scholar
  57. 57.
    Zhao HQ, Wei Y, Xu J, Kan J, Su WP, Hong MC. Pd/PR3-catalyzed cross-coupling of aromatic carboxylic acids with electron-deficient polyfluoroarenes via combination of decarboxylation with sp2 C-H cleavage. J Org Chem, 2011, 76: 882–893CrossRefGoogle Scholar
  58. 58.
    Wang CY, Rakshit S, Glorius F. Palladium-catalyzed intermolecular decarboxylative coupling of 2-phenylbenzoic acids with alkynes via C-H and C-C bond activation. J Am Chem Soc, 2010, 132: 14006–14008CrossRefGoogle Scholar
  59. 59.
    Yamashita M, Hirano K, Satoh T, Miura M. Synthesis of condensed heteroaromatic compounds by palladium-catalyzed oxidative coupling of heteroarene carboxylic acids with alkynes. Org Lett, 2009, 11: 2337–2340CrossRefGoogle Scholar
  60. 60.
    Zhang M, Zhou J, Kan J, Wang M, Su WP, Hong MC. Pd-catalyzed cross-coupling of carboxylic acids with nitroethane via combination of decarboxylation and dehydrogenation. Chem Commun, 2010, 46: 5455–5457CrossRefGoogle Scholar
  61. 61.
    Yu M, Pan DL, Jia W, Chen W, Jiao N. Copper-catalyzed decarboxylative cross-coupling of propiolic acids and terminal alkynes. Tetrahedron Lett, 2010, 51: 1287–1290CrossRefGoogle Scholar
  62. 62.
    Bi HP, Zhao L, Liang YM, Li CJ. The copper-catalyzed decarboxylative coupling of the sp3-hybridized carbon atoms of α-amino acids. Angew Chem Int Ed, 2009, 48: 792–795CrossRefGoogle Scholar
  63. 63.
    Bi HP, Teng QF, Guan M, Chen WW, Liang YM, Yao XJ, Li CJ. Aldehyde- and ketone-induced tandem decarboxylation-coupling (Csp3-Csp) of natural α-amino acids and alkynes. J Org Chem, 2010, 75: 783–788CrossRefGoogle Scholar
  64. 64.
    Feng C, Loh T-P. Palladium-catalyzed decarboxylative cross-coupling of alkynyl carboxylic acids with arylboronic acids. Chem Commun, 2010, 46: 4779–4781CrossRefGoogle Scholar
  65. 65.
    Dai JJ, Liu JH, Luo DF, Liu L. Pd-catalyzed decarboxylative Suzuki reactions and orthogonal Cu-based O-arylation of aromatic carboxylic acids. Chem Commun, 2011, 47: 677–679CrossRefGoogle Scholar
  66. 66.
    Li M, Wang C, Ge H. Pd(II)-catalyzed decarboxylative cross-coupling of potassium aryltrifluoroborates with α-oxocarboxylic acids at room temperature. Org Lett, 2011, 13: 2062–2064CrossRefGoogle Scholar
  67. 67.
    Li MZ, Wang C, Fang P, Ge HB. Pd(II)-catalyzed decarboxylative cross-coupling of oxamic acids with potassium phenyltrifluoroborates under mild conditions. Chem Commun, 2011, 47: 6587–6589CrossRefGoogle Scholar
  68. 68.
    Cornella J, Lahlali H, Larrosa I. Decarboxylative homocoupling of (hetero)aromatic carboxylic acids. Chem Commun, 2010, 46: 8276–8278CrossRefGoogle Scholar
  69. 69.
    Park J, Park E, Kim A, Park S-A, Lee Y, Chi K-W, Jung YH, Kim IS. Pd-catalyzed decarboxylative coupling of propiolic acids: one-pot synthesis of 1,4-disubstituted 1,3-diynes via Sonogashira-homocou-pling sequence. J Org Chem, 2011, 76: 2214–2219CrossRefGoogle Scholar
  70. 70.
    Jia W, Jiao N. Cu-catalyzed oxidative amidation of propiolic acids under air via decarboxylative coupling. Org Lett, 2010, 12: 2000–2003CrossRefGoogle Scholar
  71. 71.
    Duan ZY, Ranjit S, Zhang PF, Liu XG. Synthesis of aryl sulfides by decarboxylative C S cross-couplings. Chem Eur J, 2009, 15: 3666–3669CrossRefGoogle Scholar
  72. 72.
    Ranjit S, Duan Z, Zhang P, Liu X. Synthesis of vinyl sulfides by copper-catalyzed decarboxylative C-S cross-coupling. Org Lett, 2010, 12: 4134–4136CrossRefGoogle Scholar
  73. 73.
    Hu J, Zhao N, Yang B, Wang G, Guo LN, Liang YM, Yang SD. Copper-catalyzed C-P coupling through decarboxylation. Chem Eur J, 2011, 17: 5516–5521CrossRefGoogle Scholar
  74. 74.
    Luo Y, Pan XL, Wu J. Silver-catalyzed decarboxylative halogenation of carboxylic acids. Tetrahedron Lett, 2010, 51: 6646–6648CrossRefGoogle Scholar
  75. 75.
    Luo Y, Wu J. Palladium-catalyzed decarboxylative 1,2-addition of carboxylic acids to aldehydes or imines. Chem Commun, 2010, 46: 3785–3787CrossRefGoogle Scholar
  76. 76.
    Lalic G, Aloise AD, Shair MD. An exceptionally mild catalytic thioester aldol reaction inspired by polyketide biosynthesis. J Am Chem Soc, 2003, 125: 2852–2853CrossRefGoogle Scholar
  77. 77.
    Magdziak D, Lalic G, Lee HM, Fortner KC, Aloise AD, Shair MD. Catalytic enantioselective thioester aldol reactions that are compatible with protic functional groups. J Am Chem Soc, 2005, 127: 7284–7285CrossRefGoogle Scholar
  78. 78.
    Yin L, Kanai M, Shibasaki M. Nucleophile generation via decarboxylation: Asymmetric construction of contiguous trisubstituted and quaternary stereocenters through a Cu(I)-catalyzed decarboxylative Mannich-type reaction. J Am Chem Soc, 2009, 131: 9610–9611CrossRefGoogle Scholar
  79. 79.
    Yamashita M, Hirano K, Satoh T, Miura M. Synthesis of 1,4-diarylbuta-1,3-dienes through palladium-catalyzed decarboxylative coupling of unsaturated carboxylic acids. Adv Synth Catal, 2011, 353: 631–636CrossRefGoogle Scholar
  80. 80.
    Lindh J, Sjöberg PJR, Larhed M. Synthesis of aryl ketones by palladium( II)-catalyzed decarboxylative addition of benzoic acids to nitriles. Angew Chem Int Ed, 2010, 49: 7733–7737CrossRefGoogle Scholar
  81. 81.
    Sun ZM, Zhao PJ. Rhodium-mediated decarboxylative conjugate addition of fluorinated benzoic acids: Stoichiometric and catalytic transformations. Angew Chem Int Ed, 2009, 48: 6726–6730CrossRefGoogle Scholar
  82. 82.
    Weaver JD, Recio III A, Grenning AJ, Tunge JA. Transition metal-catalyzed decarboxylative allylation and benzylation reactions. Chem Rev, 2011, 111, 1846–1913CrossRefGoogle Scholar

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© Science China Press and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education); Department of ChemistryTsinghua UniversityBeijingChina
  2. 2.State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiChina

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