Iodine-catalyzed regioselective C-3 arylation of indoles with p-quinols


Iodine-mediated highly convenient strategy for the C-3 arylation of indoles with p-quinols is presented. The present work surpasses in forming a C–C bond at the meta-position of the phenols, which is traditionally challenging to functionalize. This protocol further leads the way to have ascendable, forthright access to phenol-assimilated heterocycles which have powerful applications both in synthetic and medicinal chemistry.

Graphic abstract

Iodine-mediated highly convenient and rapid protocol for C-3 arylation of indoles with p-quinols is presented. This methodology utilizes readily available indoles, furans and thiophene for Michael addition to p-quinols and subsequent aromatization to access phenol-assimilated heterocycles which have powerful applications both in synthetic and medicinal chemistry.

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

Figure 1
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Figure 2


  1. 1.

    Garcia-Garcia C, Laura O -R, Álvarez S, Álvarez R, Ribagorda M and Carreño M C 2016 Friedel–Craft Alkylation of Indoles with p-Quinols: The role of hydrogen bonding of water for the desymmetrization of the cyclohexadienone system Org. Lett. 18 2224

    CAS  Google Scholar 

  2. 2.

    Kochanowska-Karamyan A J and Hamann M T 2010 Marine indole alkaloids: potential new drug leads for the control of depression and anxiety Chem. Rev. 110 4489

    CAS  Google Scholar 

  3. 3.

    Llona-Minguez S, Desroses M, Ghassemian A, Jacques S A, Eriksson L, Isacksson R, Koolmeister T, Stenmark P, Scobie M and Helleday T 2015 Vinylic MIDA boronates: new building blocks for the synthesis of aza-heterocycles Chem.- A Eur. J. 21 7394

  4. 4.

    Aboul-Enein H Y, Kruk I, Lichszteld K, Michalska T, Kladna A, Marczynski S and Ölgen S 2004 Scavenging of reactive oxygen spicies by N-substituted indole-2 and 3-carboxamides Luminescence 19 1

    CAS  Article  Google Scholar 

  5. 5.

    Falcó J L, Piqué M, González M, Buira I, Méndez E, Terencio J, Pérez C, Príncep M, Palomer A and Guglietta A 2006 Synthesis, pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as potent GABAA agonists Eur. J. Med. Chem. 41 985

    Article  Google Scholar 

  6. 6.

    Nematollahi D and Hedayatfar V 2011 Diversity in electrochemical oxidation of dihydroxybezenes in the presence of 1-methylindole J. Chem. Sci. 123 709

    CAS  Article  Google Scholar 

  7. 7.

    Hsieh M-F, Rao P D and Liao C-C 1999 Diels-Alder and Michael addition reactions of indoles with masked o-benzoquinones: synthesis of highly functionalized hydrocarbazoles and 3-arylindoles Chem. Commun. 1441

  8. 8.

    Ovaska T V 2011 Synthesis of cycloheptanoid natural products via a tandem 5-exo-cyclization/claisen rearrangement process ARKIVOC v 34

    Google Scholar 

  9. 9.

    Sunasee R and Clive D L J 2010 Desymmetrization of 4-hydroxy-2,5-cyclohexadienones by radical cyclization: synthesis of optically pure γ-lactones Chem. Commun. 46 701

    CAS  Google Scholar 

  10. 10.

    Zilbeyaz K, Sahin E and Kilic H 2007 Synthesis of enantiometrically pure analogues of the meta-substituted aniline antibiotics Tetrahedron: Asymm. 18 791

    CAS  Google Scholar 

  11. 11.

    Patil A D, Freyer A J, Killmer L, Offen P, Carte B, Jurewiz A J and Johnson R K 1997 Frondosins, five new sesquiterpene hydroquinone derivatives with novel skeletons from the sponge Dysidea frondosa: inhibitors of interleukin-8 receptors Tetrahedron 53 5047

    CAS  Article  Google Scholar 

  12. 12.

    Felpin F-X 2007 Oxidation of 4-arylphenol trimethylsilyl ether to p-arylphenol trimethyl ethers to p-arylquinols using hypervalent iodine(III) reagents Tetrahedron Lett. 48 409

    CAS  Article  Google Scholar 

  13. 13.

    Tello-Aburto R, Kalstabakken K A, Volp K A and Harned A M 2011 Regioselective and stereoselective cyclizations of cyclohexadienones tethered to active methylene groups. Org. Biomol. Chem. 9 7849

    CAS  Article  Google Scholar 

  14. 14.

    Vasquez-Cespedes S, Chepiga K M, Möller N, Schaefer A H and Glorius F 2016 Direct C-H arylation of heteroarenes with copper impregnated on magnetite as a reusable catalyst: Evidence for CuO nanoparticle catalysis in solution ACS Catal. 6 5954

    CAS  Google Scholar 

  15. 15.

    Phipps R J, Grimster N P and Gaunt M J 2008 Cu(II)-catalysed direct and site-selective arylation of indoles under mild conditions J. Am. Chem. Soc. 130 8172

    CAS  Article  Google Scholar 

  16. 16.

    Joucla L and Djakovitch L 2009 Transition metal-catalysed, direct and site-selective N1-, C2- or C3-arylation of the indole nucleus. 20 years of improvements Adv. Synth. Catal. 351 673

    CAS  Article  Google Scholar 

  17. 17.

    Sharma K, Baral E R, Akhtar M S, Lee Y R, Kim S H and Wee Y-J 2017 3-Naphthylindoles as new promising candidate antioxidant, antibacterial and antibiofim agents Res. Chem. Intermed. 43 2387

    CAS  Article  Google Scholar 

  18. 18.

    Baral E R, Lee Y R and Kim S H 2015 3-Naphthylindole construction by rhodium(II)-catalyzed regioselective direct arylatin of indoles with 1-diazonaphthalen-2-(1H)-ones Adv. Synth. Catal. 357 2883

    CAS  Article  Google Scholar 

  19. 19.

    Yang Y, Qiu X, Zhao Y, Mu Y and Shi Z 2016 Palladium-catalyzed C-H arylation of indoles at the C7 position J. Am. Chem. Soc. 138 495

    CAS  Article  Google Scholar 

  20. 20.

    Ackerman L, Barfüßer S 2009 Palladium-catalysed direct C-3 aryations of indoles with an air-stable HASPO Synlett 5 808

    Article  Google Scholar 

  21. 21.

    Perato S, Large B, Lu Q, Gaucher A and Prim D 2016 Pyridylmethylamine-Palladium catalytic systems: A selective alternative in the C-H arylation of indole ChemCatChem. 9 389

    Article  Google Scholar 

  22. 22.

    Yamaguchi M, Suzuki K, Sato Y and Manabe K 2017 Palladium-catalyzed direct C3-selective arylation of N-unsubstituted indoles with aryl chlorides and triflates Lett. 19 5388

    CAS  Google Scholar 

  23. 23.

    Sandtorv A H 2015 Transition metal catalyzed C-H activation of indoles Adv. Synth. Catal. 357 2403

    CAS  Article  Google Scholar 

  24. 24.

    Cornella J, Lu P and Larrosa I 2009 Intermolecular decarboxylative direct C-3 arylation of indoles with benzoic acid Org. Lett. 11 5506

    CAS  Article  Google Scholar 

  25. 25.

    Veisi H and Morakabati N 2015 Palladium nanoparticles supported on modified single-walled carbon nanotubes: a heterogeneous and reusable catalyst in the ullman-type N-arylation of imidazole and indoles New J. Chem. 39 2901

    CAS  Article  Google Scholar 

  26. 26.

    Chen Y, Guo S, Li K, Qu J, Yuan H, Hua Q and Chena B 2013 Palladium-catalyzed direct dinitrogenative C-3 arylation of 1H-indoles with aryl hydrazines using air as the oxidant Adv. Synth. Catal. 355 711

    CAS  Article  Google Scholar 

  27. 27.

    Koulouri S, Malamidou-Xenikaki E and Spyroudis S 2005 Acid-catalyzed addition of indoles to hydroxyquinones Tetrahedron 61 10894

    CAS  Google Scholar 

  28. 28.

    Zhang Y-P, Feng X-L, Yang Y –S and Cao B-X 2016 Metal-free, C-H arylation of indole and its derivative with aryl diazonium salts by visible-light photoredox catalysis Tetrahedron Lett. 57 2298

    CAS  Article  Google Scholar 

  29. 29.

    Ye Y, Wang H and Fan R 2011 meta-Selective substitution of phenols with indoles via one-pot oxidative dearomatization-Michael addition-aromatization Synlett 7 923

    Google Scholar 

  30. 30.

    CCDC number of compound 15 is 1877135

Download references


We thank the Department of Science Technology (DST) for providing HRMS facility in the FIST program, and ND thanks the MHRD, New Delhi for a research fellowship.

Author information



Corresponding author

Correspondence to Rama Krishna Peddinti.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 3332 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dua, N., Peddinti, R.K. Iodine-catalyzed regioselective C-3 arylation of indoles with p-quinols. J Chem Sci 132, 45 (2020).

Download citation


  • C-3 arylation of indoles
  • meta-functionalized phenols
  • indole-phenol hybrids
  • regioselective reaction