Skip to main content
SpringerLink
Log in

Mechanistic study of copper-catalyzed intramolecular ortho-C-H activation/carbon-nitrogen and carbon-oxygen cyclizations

  • Articles
  • Published:
Science China Chemistry Aims and scope Submit manuscript

Abstract

Intramolecular ortho-C-H activation and C-N/C-O cyclizations of phenyl amidines and amides have recently been achieved under Cu catalysis. These reactions provide important examples of Cu-catalyzed functionalization of inert C-H bonds, but their mechanisms remain poorly understood. In the present study the several possible mechanisms including electrophilic aromatic substitution, concerted metalation-deprotonation (CMD), Friedel-Crafts mechanism, radical mechanism, and proton-coupled electron transfer have been theoretically examined. Cu(II)-assisted CMD mechanism is found to be the most feasible for both C-O and C-N cyclizations. This mechanism includes three steps, i.e. CMD with Cu(II), oxidation of the Cu(II) intermediate, and reductive elimination from Cu(III). Our calculations show that Cu(II) mediates the C-H activation through an six-membered ring CMD transition state similar to that proposed for many Pd-catalyzed C-H activation reactions. It is also interesting to find that the rate-limiting steps are different for C-N and C-O cyclizations: for the former it is concerted metalation-deprotonation with Cu(II), whereas for the latter it is reductive elimination from Cu(III). The above conclusions are consistent with the experimental kinetic isotope effects (1.0 and 2.1 for C-O and C-N cyclizations, respectively), substituent effects, and the reactions under O2-free conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Balcells D, Clot E, Eisenstein O. C-H bond activation in transition metal species from a computational perspective. Chem Rev, 2010, 110: 749–823

    Article  CAS  Google Scholar 

  2. Colby DA, Bergman RG, Ellman JA. Rhodium-catalyzed C-C bond formation via heteroatom-directed C-H bond activation. Chem Rev, 2010, 110: 624–655

    Article  CAS  Google Scholar 

  3. Collet F, Lescot C, Dauban P. Catalytic C-H amination: The stereoselectivity issue. Chem Soc Rev, 2011, 40: 1926–1936

    Article  CAS  Google Scholar 

  4. Lyons TW, Sanford MS. Palladium-catalyzed ligand-directed C-H functionalization reactions. Chem Rev, 2010, 110: 1147–1169

    Article  CAS  Google Scholar 

  5. Xu LM, Li BJ, Yang Z, Shi ZJ. Organopalladium(IV) chemistry. Chem Soc Rev, 2010, 39: 712–733

    Article  CAS  Google Scholar 

  6. For recent examples, see: c) Wang DH, Engle KM, Shi BF, Yu JQ. Ligand-enabled reactivity and selectivity in a synthetically versatile aryl C-H olefination. Science, 2010, 327: 315–319

    Article  CAS  Google Scholar 

  7. Mandal D, Yamaguchi AD, Yamaguchi J, Itami K. Synthesis of dragmacidin D via direct C-H couplings. J Am Chem Soc, 2011, 133: 19660–19663

    Article  CAS  Google Scholar 

  8. Xiao B, Gong TJ, Liu ZJ, Liu JH, Luo DF, Xu J, Liu L. Synthesis of dibenzofurans via palladium-catalyzed phenol-directed C-H activation/C-O cyclization. J Am Chem Soc, 2011, 133: 9250–9253

    Article  CAS  Google Scholar 

  9. Xiao B, Gong TJ, Xu J, Liu ZJ, Liu L. Palladium-catalyzed intermolecular directed C-H amidation of aromatic ketones. J Am Chem Soc, 2011, 133: 1466–1474

    Article  CAS  Google Scholar 

  10. Ueda K, Yanagisawa S, Yamaguchi J, Itami K. A general catalyst for the β-selective C-H bond arylation of thiophenes with iodoarenes. Angew Chem Int Ed, 2010, 49: 8946–8949

    Article  CAS  Google Scholar 

  11. Dai HX, Yu JQ. Pd-catalyzed oxidative ortho-C-H borylation of arenes. J Am Chem Soc, 2012, 134: 134–137

    Article  CAS  Google Scholar 

  12. Wasa M, Engle KM, Lin DW, Yoo EJ, Yu JQ. Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes. J Am Chem Soc, 2011, 133: 19598–19601

    Article  CAS  Google Scholar 

  13. Wendlandt AE, Suess AM, Stahl SS. Copper-catalyzed aerobic oxidative C-H functionalizations: Trends and mechanistic insights. Angew Chem Int Ed, 2011, 50: 11062–11087

    Article  CAS  Google Scholar 

  14. Yang L, Lu Z, Stahl SS. Regioselective copper-catalyzed chlorination and bromination of arenes with O2 as the oxidant. Chem Commun, 2009, 6460–6462

  15. Li Z, Bohle DS, Li CJ. Cu-catalyzed cross-dehydrogenative coupling: A versatile strategy for C-C bond formations via the oxidative activation of sp(3) C-H bonds. Proc Natl Acad Sci U S A, 2006, 103: 8928–8933

    Article  CAS  Google Scholar 

  16. Do HQ, Daugulis O. Copper-catalyzed arylation of heterocycle C-H bonds. J Am Chem Soc, 2007, 129: 12404–12405

    Article  CAS  Google Scholar 

  17. Do HQ, Daugulis O. Copper-catalyzed arylation and alkenylation of polyfluoroarene C-H bonds. J Am Chem Soc, 2008, 130: 1128–1129

    Article  CAS  Google Scholar 

  18. Chen X, Hao XS, Goodhue CE, Yu JQ. Cu(II)-catalyzed functionalizations of aryl C-H bonds using O2 as an oxidant. J Am Chem Soc, 2006, 128: 6790–6791

    Article  CAS  Google Scholar 

  19. Brasche G, Buchwald SL. C-H functionalization/C-N bond formation: Copper-catalyzed synthesis of benzimidazoles from amidines. Angew Chem Int Ed, 2008, 47: 1932–1934

    Article  CAS  Google Scholar 

  20. Ueda S, Nagasawa H. Synthesis of 2-arylbenzoxazoles by copper-catalyzed intramolecular oxidative C-O coupling of benzanilides. Angew Chem Int Ed, 2008, 47: 6411–6413

    Article  CAS  Google Scholar 

  21. Ueda S, Nagasawa H. Copper-catalyzed synthesis of benzoxazoles via a regioselective C-H functionalization/C-O bond formation under an air atmosphere. J Org Chem 2009, 74: 4272–4277

    Article  CAS  Google Scholar 

  22. Ribas X, Calle C, Poater A, Casitas A, Gomez L, Xifra R, Parella T Benet-Buchholz J, Schweiger A, Mitrikas G, Sola M, Llobet A, Stack TD. Facile C-H bond cleavage via a proton-coupled electron transfer involving a C-H…Cu(II) interaction. J Am Chem Soc, 2010, 132: 12299–12306

    Article  CAS  Google Scholar 

  23. Yao B, Wang DX, Huang ZT, Wang MX. Room-temperature aerobic formation of a stable aryl-Cu(III) complex and its reactions with nucleophiles: Highly efficient and diverse arene C-H functionalizations of azacalix[1]arene[3]pyridine. Chem Commun, 2009, 2899–2901

  24. Wang ZL, Zhan L, Wang MX. Regiospecific functionalization of azacalixaromatics through copper-mediated aryl C-H activation and C-O bond formation. Org Lett, 2011, 13: 6560–6563

    Article  CAS  Google Scholar 

  25. Huffman LM, Casitas A, Font M, Canta M, Costas M, Ribas X, Stahl SS. Observation and mechanistic study of facile C-O bond formation between a well-defined aryl-copper(III) complex and oxygen nucleophiles. Chem Eur J, 2011, 17: 10643–10650

    Article  CAS  Google Scholar 

  26. Huffman LM, Stahl SS. Carbon-nitrogen bond formation involving well-defined aryl-copper(III) complexes. J Am Chem Soc, 2008, 130: 9196–9197

    Article  CAS  Google Scholar 

  27. Garcia-Lopez J, Yanez-Rodriguez V, Roces L, Garcia-Granda S, Martinez A, Guevara-Garcia A, Castro GR, Jimenez-Villacorta F, Iglesias MJ, Lopez Ortiz F. Synthesis and characterization of a coupled binuclear Cu(I)/Cu(III) complex. J Am Chem Soc, 2010, 132: 10665–10667

    Article  CAS  Google Scholar 

  28. Chen B, Hou XL, Li YX, Wu YD. Mechanistic understanding of the unexpected meta selectivity in copper-catalyzed anilide C-H bond arylation. J Am Chem Soc, 2011, 133: 7668–7671

    Article  CAS  Google Scholar 

  29. Wang M, Fan T, Lin Z. DFT Studies on copper-catalyzed arylation of aromatic C-H Bonds. Organometallics, 2012, 31: 560–569

    Article  Google Scholar 

  30. Santoro S, Liao RZ, Himo F. Theoretical study of mechanism and selectivity of copper-catalyzed C-H bond amidation of indoles. J Org Chem, 2011, 76: 9246–9252

    Article  CAS  Google Scholar 

  31. Gorelsky SI, Lapointe D, Fagnou K. Analysis of the concerted metalation-deprotonation mechanism in palladium-catalyzed direct arylation across a broad range of aromatic substrates. J Am Chem Soc, 2008, 130: 10848–10849

    Article  CAS  Google Scholar 

  32. García-Cuadrado D, Mendoza P De; Braga AAC, Maseras F, Echavarren AM. Proton-abstraction mechanism in the palladium-catalyzed intramolecular arylation: Substituent effects. J Am Chem Soc, 2007, 129: 6880–6886

    Article  Google Scholar 

  33. Kruszewski J, Krygowski TM. Definition of aromaticity Basing on the harmonic oscillator model. Tetrahedron Lett, 1972, 13: 3839–3842

    Article  Google Scholar 

  34. Krygowski TM, Cyrañski MK. Structural aspects of aromaticity. Chem Rev, 2001, 101: 1385–1419

    Article  CAS  Google Scholar 

  35. NICS(1) estimated at 1A above the center of the ring. For details see: Schleyer PvR, Maerker C, Dransfeld A, Jiao H, van Eikema Hommes NJR. Nucleus-independent chemical shifts: A simple and efficient aromaticity probe. J Am Chem Soc, 1996, 118: 6317–6318

    Article  CAS  Google Scholar 

  36. Yu HZ, Jiang YY, Fu Y, Liu L. Alternative mechanistic explanation for ligand-dependent selectivities in copper-catalyzed N- and O-arylation reactions. J Am Chem Soc, 2010, 132: 18078–18091

    Article  CAS  Google Scholar 

  37. Zhang SL, Liu L, Fu Y, Guo QX. Theoretical study on copper(I)-catalyzed cross-coupling between aryl halides and amides. Organometallics, 2007, 26: 4546–4554

    Article  CAS  Google Scholar 

  38. Casitas A, King AE, Parella T, Costas M, Stahl SS, Ribas X. Direct observation of CuI/CuIII redox steps relevant to Ullmann-type coupling reactions. Chem Sci, 2010, 1: 326–330

    Article  CAS  Google Scholar 

  39. Note that O-Int1 is found to be the most stable. See Supporting Information for details.

  40. Ribas X, Jackson DA, Donnadieu B, Mahia J, Parella T, Xifra R, Hedman B, Hodgson KO, Llobet A, Stack TDP. Aryl C-H activation by CuII to form an organometallic aryl-CuIII species: A novel twist on copper disproportionation. Angew Chem In Ed, 2002, 41: 2991–2994

    Article  CAS  Google Scholar 

  41. King AE, Brunold TC, Stahl SS. Mechanistic study of copper-catalyzed aerobic oxidative coupling of arylboronic esters and methanol: Insights into an organometallic oxidase reaction. J Am Chem Soc, 2009, 131: 5044–5045

    Article  CAS  Google Scholar 

  42. Huffman LM, Casitas A, Font M, Canta M, Costas M, Ribas X, Stahl SS. Observation and mechanistic study of facile C-O bond formation between a well-defined aryl-copper(III) complex and oxygen nucleophiles. Chem Eur J, 2011, 17: 10642–10649

    Article  Google Scholar 

  43. Sartori G, Maggi R. Use of solid catalysts in Friedel-Crafts acylation reactions. Chem Rev, 2006, 106: 1077–1104

    Article  CAS  Google Scholar 

  44. Kuang GC, Guha PM, Brotherton WS, Simmons JT, Stankee LA, Nguyen BT, Clark RJ, Zhu L. Experimental investigation on the mechanism of chelation-assisted, copper(II) acetate-accelerated azide-alkyne cycloaddition. J Am Chem Soc, 2011, 133: 13984–14001

    Article  CAS  Google Scholar 

  45. An alternative intermediate (i.e. Cu-nitrene may also be involved as proposed by Buchwald et al. for the C-N cyclization. However, our calculation shows that the formation of Cu-nitrene is highly endergonic (+35.2 kcal/mol) and therefore unfavorable (Figure 8).

  46. For details about the disfavored routes, see Supporting Information.

  47. Jones GO, Liu P, Houk KN, Buchwald SL. Computational explorations of mechanisms and ligand-directed selectivities of copper-catalyzed Ullmann-type reactions. J Am Chem Soc, 2010, 132: 6205–6213

    Article  CAS  Google Scholar 

  48. In the case of C-O formation reaction with radical scavenger, the small decrease of yield is probably attributed to radical species or other alkene-promoted side-reactions. To further clarify the radical pathways, we calculated the important radical species O-6 and O-8. The data suggested that the radical pathway might be not plausible.

  49. Lanci MP, Remy MS, Kaminsky W, Mayer JM, Sanford MS. Oxidatively induced reductive elimination from ((t)Bu2bpy)Pd(Me)2: Palladium( IV) intermediates in a one-electron oxidation reaction. J Am Chem Soc, 2009, 131: 15618–15620

    Article  CAS  Google Scholar 

  50. The wavefunction is stable under the perturbations considered.

  51. Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys, 1993, 98: 5648–5652

    Article  CAS  Google Scholar 

  52. Perdew JP. Density-functional approximation for the correlation energy of the inhomogeneous electron gas. J Phys Rev B, 1986, 33: 8822–8824

    Article  Google Scholar 

  53. Rassolov VA, Pople JA, Ratner MA, Windus TL. 6-31G* basis set for atoms K through Zn. J Chem Phy, 1998, 109: 1223–1229

    Article  CAS  Google Scholar 

  54. Pavelka M, Šimánek M, Šponer J, Burda JV. Copper cation interactions with biologically essential types of ligands: A computational DFT study. J Phys Chem A, 2006, 110: 4795–4809

    Article  CAS  Google Scholar 

  55. Li Z, Fu Y, Zhang SL, Guo QX, Liu L. Heck-type reactions of imine derivatives: A DFT study. Chem Asian J, 2010, 5: 1475–1486

    CAS  Google Scholar 

  56. 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: 14391–14393

    Article  CAS  Google Scholar 

  57. 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: 638–646

    Article  CAS  Google Scholar 

  58. 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: 9350–9354

    Article  CAS  Google Scholar 

  59. Li Z, Zhang SL, Fu Y, Guo QX, Liu L. Mechanism of Ni-catalyzed selective C-O bond activation in cross-coupling of aryl esters. J Am Chem Soc, 2009, 131:8815–8823

    Article  CAS  Google Scholar 

  60. Gonzalez C, Schlegel HB. An Improved Algorithm for Reaction Path Following. J Chem Phys, 1989, 90: 2154–2161

    Article  CAS  Google Scholar 

  61. Truhlar DG, Zhao Y. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc, 2008, 120: 215–241

    Article  Google Scholar 

  62. Ariafard A, Zarkoob F, Batebi H, Stranger R, Yates BF. DFT Studies on the carboxylation of the C-H bond of heteroarenes by copper(I) complexes. Organometallics, 2011, 30: 6218–6224

    Article  CAS  Google Scholar 

  63. Cramer CJ, Marenich AV, Truhlar DG. Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B, 2009, 113: 6378–6396

    Article  Google Scholar 

  64. Gaussian 09, Revision B. 01, Frisch MJ, Trucks GW, Schlegel HB, et al. Wallingford CT: Gaussian Inc. 2010

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China

    ShiYa Tang, TianJun Gong & Yao Fu

Authors
  1. ShiYa Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. TianJun Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yao Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yao Fu.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tang, S., Gong, T. & Fu, Y. Mechanistic study of copper-catalyzed intramolecular ortho-C-H activation/carbon-nitrogen and carbon-oxygen cyclizations. Sci. China Chem. 56, 619–632 (2013). https://doi.org/10.1007/s11426-012-4795-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-012-4795-3

Keywords

Search

Navigation