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Inventing Reactions pp 91–119Cite as

The Discovery and Development of a Palladium(II)-Catalyzed Oxidative Cross-Coupling of Two Unactivated Arenes

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Part of the book series: Topics in Organometallic Chemistry ((TOPORGAN,volume 44))

Abstract

The process of discovery and development of a palladium(II)-catalyzed oxidative cross-coupling of N-acetyl and N-pivaloylindoles with simple aromatic compounds is described. Within this process our inspiration was primarily derived from the organometallic literature and in particular the recent emergence of new and novel mechanisms for C–H bond cleavage by Pd(II)-complexes. During these studies it was realized that high levels of regio-control for C–H bond cleavage at indole could be obtained and a subsequent investigation has led to the proposal of a C3,C2-palladium migration for the C2-arylation of N-pivaloylindole. The current state of the art in transition-metal catalyzed oxidative cross-coupling is also presented.

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Abbreviations

[O]:

Oxidant

Ac:

Acetyl

acac:

Acetylacetonate

AcO− :

Acetate

BQ:

Benzoquinone

CMD:

Concerted metalation–deprotonation

DFT:

Density functional theory

DMA:

N,N-dimethylacetamide

DMF:

N,N-dimethylformamide

DMSO:

Dimethylsulfoxide

M:

Metal pre-activating group (BR2, SnR3, etc.)

Me:

Methyl

Ph:

Phenyl

Piv:

Pivaloyl

PivO− :

Pivalate

Py:

Pyridine

R:

Carbon-containing organic functional group

t-Am:

tert-Amyl

TBAB:

Tetrbutylammonium bromide

t-Bu:

tert-Butyl

TFA:

Trifluoroacetate

References

  1. Bringmann G, Günther C, Ochse O, Schupp O, Tasler S (2001) Progress in the chemistry of organic natural products. Springer, Wien/New York

    Google Scholar 

  2. Lessene G, Feldman KS (2002) Oxidative aryl-coupling reactions in synthesis. In: Astruc D (ed) Modern arene chemistry. Wiley-VCH, Weinheim

    Google Scholar 

  3. Hassan J, Svignon M, Gozzi C, Schultz E, Lemaire M (2002) Aryl-aryl bond formation one century after the discovery of the Ullman reaction. Chem Rev 102:1359–1469

    Article  CAS  Google Scholar 

  4. Diederich F, Stang PJ (eds) (2004) Metal-catalyzed cross-coupling reactions. Wiley-VCH, New York

    Google Scholar 

  5. Suzuki A (2011) Cross-coupling reactions of organoboranes: an easy way to construct C-C bonds (Nobel lecture). Angew Chem Int Ed 50:6722–6737

    Article  CAS  Google Scholar 

  6. Negishi E (2011) Magical power of transition metal: past, present, and future (Nobel lecture). Angew Chem Int Ed 50:6738–6764

    Article  CAS  Google Scholar 

  7. Alberico D, Scott ME, Lautens M (2007) Aryl-aryl bond formation by transition-metal-catalyzed direct arylation. Chem Rev 107:174–238

    Article  CAS  Google Scholar 

  8. Campeau L-C, Stuart DR, Fagnou K (2007) Recent advances in intermolecular direct arylation reactions. Aldrichmica Acta 40:35–41

    CAS  Google Scholar 

  9. Seregin IV, Gevorgyan V (2007) Direct transition-metal-catalyzed functionalization of heteroaromatic compounds. Chem Soc Rev 36:1173–1193

    Article  CAS  Google Scholar 

  10. Colby DA, Bergman RG, Ellman JA (2009) Rhodium-catalyzed C-C bond formation via heteroatom-directed C-H bond activation. Chem Rev 110:624–655

    Article  Google Scholar 

  11. Liu C, Zhang H, Shi W, Lei A (2011) Bond formations between two nucleophiles: transition metal catalyzed oxidative cross-coupling reactions. Chem Rev 111:1780–1824

    Article  CAS  Google Scholar 

  12. Ryabov AD, Sakodinskaya IK, Yatsimirsky AK (1985) Kinetics and mechanism of ortho-palladation of ring-substituted N,N-dimethylbenzylamines. J Chem Soc Dalton Trans 2629

    Google Scholar 

  13. Ryabov AD (1990) Mechanisms of intramolecular activation of carbon-hydrogen bonds in transition-metal complexes. Chem Rev 90:403–424

    Article  CAS  Google Scholar 

  14. Lafrance M, Fagnou K (2006) Palladium-catalyzed benzene arylation: incorporation of catalytic pivalic acid as a proton shuttle and a key element in catalyst design. J Am Chem Soc 128:16496–16497

    Article  CAS  Google Scholar 

  15. Campeau L-C, Rousseaux S, Fagnou K (2005) A solution to the 2-pyridyl organometallic cross-coupling problem: regioselective catalytic direct arylation of pyridine N-oxides. J Am Chem Soc 127:18020–18021

    Article  CAS  Google Scholar 

  16. Leclerc J-P, Fagnou K (2006) Palladium-catalyzed cross-coupling reactions of diazine N-oxides with aryl chlorides, bromides and iodides. Angew Chem Int Ed 45:7781–7786

    Article  CAS  Google Scholar 

  17. Campeau L-C, Stuart DR, Leclerc JP, Bertrand-Laperle M, Villemure E, Sun H-Y, Lasserre S, Guimond N, Lecavallier M, Fagnou K (2009) Palladium-catalyzed direct arylation of azine and azole N-oxides: reaction development, scope and applications in synthesis. J Am Chem Soc 131:3291–3306

    Article  CAS  Google Scholar 

  18. Sun H-Y, Gorelsky SI, Stuart DR, Campeau L-C, Fagnou K (2010) Mechanistic analysis of azine N-oxide direct arylation: evidence for a critical role of acetate in the Pd(OAc)2 precatalyst. J Org Chem 75:8180–8189

    Article  CAS  Google Scholar 

  19. Lafrance M, Rowley CN, Woo TK, Fagnou K (2006) Catalytic intermolecular direct arylation of perfluorobenzenes. J Am Chem Soc 128:8754–8756

    Article  CAS  Google Scholar 

  20. Lafrance M, Shore D, Fagnou K (2006) Mild and general conditions for the cross-coupling of aryl halides with pentafluorobenzene and other perfluoroaromatics. Org Lett 8:5097–5100

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  23. Özdemir I, Demir S, Ḉζetinkaya B, Gourlaouen C, Maseras F, Bruneau C, Dixneuf PH (2008) Direct arylation of arene C-H bonds by cooperative action of NHCarbene-ruthenium(II) catalyst and carbonate via proton abstraction mechanism. J Am Chem Soc 130:1156–1157

    Article  Google Scholar 

  24. Mota AJ, Dedieu A, Bour C, Suffert J (2005) Cyclocarbopalladation involving an unusual 1,5-palladium vinyl to aryl shift as termination step: theoretical study of the mechanism. J Am Chem Soc 127:7171–7182

    Article  CAS  Google Scholar 

  25. Lapointe D, Fagnou K (2010) Overview of the mechanistic work on the concerted metallation-deprotonation pathway. Chem Lett 39:1118–1126

    Article  Google Scholar 

  26. Huestis MP, Fagnou K (2009) Site-selective azaindole arylation at the azine and azole rings via N-oxide activation. Org Lett 11:1357–1360

    Article  CAS  Google Scholar 

  27. Labrasseur N, Larrosa I (2008) Room temperature and phosphine free palladium catalyzed direct C-2 arylation of indoles. J Am Chem Soc 130:2926–2927

    Article  Google Scholar 

  28. Deprez NR, Kalyani D, Krause A, Sanford MS (2006) Room temperature palladium-catalyzed 2-arylation of indoles. J Am Chem Soc 128:4972–4973

    Article  CAS  Google Scholar 

  29. Lane BS, Brown MA, Sames D (2005) Direct palladium-catalyzed C-2 and C-3 arylation of indoles: a mechanistic rationale for regioselectivity. J Am Chem Soc 127:8050–8057

    Article  CAS  Google Scholar 

  30. Ferreira EM, Stoltz BM (2003) Catalytic C-H bond functionalization with palladium(II): aerobic oxidative annulation of indoles. J Am Chem Soc 125:9578–9579

    Article  CAS  Google Scholar 

  31. Itahara T (1979) Intramolecular ring closure of 1-aroylindoles by palladium acetate. Synthesis 2:151–152

    Article  Google Scholar 

  32. Itahara T (1981) Arylation of N-acyl-pyrroles and -indoles with arenes and palladium acetate. J Chem Soc Chem Commun 254–255

    Google Scholar 

  33. Itahara T (1985) Arylation of aromatic heterocycles with arenes and palladium(II) acetate. J Org Chem 50:5272–5275

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  35. Stuart DR (2010) Transition-metal-catalyzed oxidative functionalization and preparation of nitrogen containing heterocycles. Ph.D. Thesis, University of Ottawa, Ottawa

    Google Scholar 

  36. Stuart DR, Villemure E, Fagnou K (2007) Elements of regiocontrol in palladium-catalyzed oxidative arene cross-coupling. J Am Chem Soc 129:12072–12073

    Article  CAS  Google Scholar 

  37. Grimster NP, Gauntlett C, Godfrey CRA, Gaunt MJ (2005) Palladium-catalyzed intermolecular alkenylation of indoles by solvent-controlled regioselective C-H functionalization. Angew Chem Int Ed 44:3125–3129

    Article  CAS  Google Scholar 

  38. Beck EM, Grimster NP, Hatley R, Gaunt MJ (2006) Mild aerobic oxidative palladium(II) catalyzed C-H bond functionalization: regioselective and switchable C-H alkenylation and annulation of pyrroles. J Am Chem Soc 128:2528–2529

    Article  CAS  Google Scholar 

  39. Dwight TA, Rue NR, Charyk D, Josselyn R, DeBoef B (2007) C-C bond formation via double C-H functionalization: aerobic oxidative coupling as a method for synthesizing heterocoupled biaryls. Org Lett 9:3137–3139

    Article  CAS  Google Scholar 

  40. Potavathri S, Dumas AS, Dwight TA, Naumiec GR, Hammann JM, DeBoef B (2008) Tetrahedron Lett 49:4050–4053

    Article  CAS  Google Scholar 

  41. Hull K, Sanford MS (2007) Catalytic and highly regioselective cross-coupling of aromatic C-H substrates. J Am Chem Soc 129:11904–11905

    Article  CAS  Google Scholar 

  42. Hull KL, Sanford MS (2009) Mechanism of benzoquinone-promoted palladium-catalyzed oxidative cross-coupling reactions. J Am Chem Soc 131:9651–9653

    Article  CAS  Google Scholar 

  43. Li B-J, Tian S-L, Fang Z, Shi Z-J (2008) Multiple C-H activations to construct biologically active molecules in a process completely free of organohalogen and organometallic components. Angew Chem Int Ed 47:1115–1118

    Article  CAS  Google Scholar 

  44. Brasche G, Garcia-Fortanet J, Buchwald SL (2008) Twofold C-H functionalization: palladium-catalyzed ortho arylation of anilides. Org Lett 10:2207–2210

    Article  CAS  Google Scholar 

  45. Cho SH, Hwang SJ, Chang S (2008) Palladium-catalyzed C-H functionalization of pyridine N-oxides: highly selective alkenylation and direct arylation with unactivated arenes. J Am Chem Soc 130:9254–9256

    Article  CAS  Google Scholar 

  46. Zhao X, Yeung CS, Dong VM (2010) Palladium-catalyzed ortho-arylation of O-phenylcarbamates with simple arenes and sodium persulfate. J Am Chem Soc 132:5837–5844

    Article  CAS  Google Scholar 

  47. He C-Y, Fan S, Zhang X (2010) Pd-catalyzed oxidative cross-coupling of perfluoroarenes with aromatic heterocycles. J Am Chem Soc 132:12850–12852

    Article  CAS  Google Scholar 

  48. Wei Y, Su W (2010) Pd(OAc)2-catalyzed oxidative C-H/C-H cross-coupling of electron-deficient polyfluoroarenes with simple arenes. J Am Chem Soc 132:16377–16379

    Article  CAS  Google Scholar 

  49. Xi P, Yang F, Qin S, Zhao D, Lan J, Gao G, Hu C, You J (2010) Palladium(II)-catalyzed oxidative C-H/C-H cross-coupling of heteroatoms. J Am Chem Soc 132:1822–1824

    Article  CAS  Google Scholar 

  50. Potavathri S, Pereira KC, Gorelsky SI, Pike A, LeBris AP, DeBoef B (2010) Regioselective oxidative arylation of indoles bearing N-alkyl protecting groups: dual C-H functionalization via a concerted metallation-deprotonation mechanism. J Am Chem Soc 132:14676–14681

    Article  CAS  Google Scholar 

  51. Malakar CC, Schmidt D, Conrad J, Beifuss U (2011) Double C-H activation: the palladium-catalyzed direct C-arylation of xanthines with arenes. Org Lett 13:1378–1381

    Article  CAS  Google Scholar 

  52. Gong X, Song G, Zhang H, Li X (2011) Palladium-catalyzed oxidative cross-coupling between pyridine and N-oxides and indoles. Org Lett 13:1766–1769

    Article  CAS  Google Scholar 

  53. Potavathri S, Kantak A, DeBoef B (2011) Increasing synthetic efficiency via direct C-H functionalization: formal synthesis of an inhibitor of botulinum neurotoxin. Chem Commun. doi: 10.1039/c1cc10755k

    Google Scholar 

  54. Lyons TW, Hull KL, Sanford MS (2011) Controlling site selectivity in Pd-catalyzed oxidative cross-coupling reactions. J Am Chem Soc 133:4455–4464

    Article  CAS  Google Scholar 

  55. Meir R, Kozuch S, Uhe A, Shaik S (2011) How can theory predict the selectivity of palladium-catalyzed cross-coupling of pristine aromatic molecules? Chem Eur J 17:7623–7631

    Article  CAS  Google Scholar 

  56. Wang X, Leow D, Yu J-Q (2011) Pd(II)-catalyzed para-selective C-H arylation of monosubstituted arenes. J Am Chem Soc 133:13864–13867

    Article  CAS  Google Scholar 

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Acknowledgements

I (DRS) will forever be indebted to Professor Keith Fagnou. His guidance, both scientifically and personally, was a constant source of inspiration during my graduate studies in his group. The entire Fagnou group is acknowledged for their support, in particular those that contributed to this chemistry: Elisia Villemure, Ivan Petrov, and Ho-Yan Sun. Sophie Rousseaux and Catherine Stuart are thanked for critical reading of this chapter at its various stages; and Prof. Gooβen is thanked for the opportunity to contribute to this anthology

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Authors and Affiliations

  1. Department of Chemistry, Centre for Catalysis Research and Innovation, University of Ottawa, 10 Marie Curie, Ottawa, Canada, K1N 6N5

    David R. Stuart & Keith Fagnou

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  1. David R. Stuart
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  2. Keith Fagnou
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Correspondence to David R. Stuart .

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  1. , FB Chemie - Organische Chemie, TU Kaiserslautern, Erwin-Schrödinger-Str. 54, Kaiserslautern, 67663, Germany

    Lukas J. Gooßen

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Stuart, D.R., Fagnou, K. (2012). The Discovery and Development of a Palladium(II)-Catalyzed Oxidative Cross-Coupling of Two Unactivated Arenes. In: Gooßen, L. (eds) Inventing Reactions. Topics in Organometallic Chemistry, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3418_2012_52

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