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Synlett 2015; 26(06): 771-778
DOI: 10.1055/s-0034-1379935
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 2-Acylated Indoles through Palladium-Catalyzed Dehydrogenative Coupling of N-Pyrimidine-Protected Indoles with Aldehydes and Ethyl Glyoxylate

Wenduo Wang
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. of China   eMail: ztanze@gmail.com
,
Jidan Liu
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. of China   eMail: ztanze@gmail.com
,
Qingwen Gui
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. of China   eMail: ztanze@gmail.com
,
Ze Tan*
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. of China   eMail: ztanze@gmail.com
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Publikationsverlauf

Received: 09. Oktober 2014

Accepted after revision: 24. November 2014

Publikationsdatum:
09. Februar 2015 (online)

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Abstract

C2-Acylated indoles have been synthesized in good yields through palladium-catalyzed dehydrogenative coupling of N-pyrimidine-protected indoles using aldehydes as the source of acyl reagent and tert-butyl hydroperoxide as the oxidant. 2-Indole carboxylates can be synthesized when aldehydes are substituted by ethyl glyoxylate.

Key words

palladium - dehydrogenative coupling - aldehyde - acylation - indoles

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1379935. Included are experimental procedures, characterization data, and copies of 1H NMR and 13C NMR spectra.
  • Supporting Information
 

  • References and Notes

    • 1a Nicolaou I, Demopoulos VJ. J. Med. Chem. 2003; 46: 417
      CrossrefPubMed
    • 1b Barreca ML, Ferro S, Rao A, Luca LD, Zappala M, Monforte AM, Debyser Z, Witvrouw M, Chimirri A. J. Med. Chem. 2005; 48: 7084
      CrossrefPubMed
    • 1c Wu Y.-S, Coumar MS, Chang J.-Y, Sun H.-Y, Kuo F.-M, Kuo C.-C, Chen Y.-J, Chang C.-Y, Hsiao C.-L, Liou J.-P. J. Med. Chem. 2009; 52: 4941
      CrossrefPubMed
    • 1d Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
      CrossrefPubMed
    • 1e Kochanowska-Karamyan AJ, Hamann MT. Chem. Rev. 2010; 110: 4489
      CrossrefPubMed
    • 1f Smith PA. J. Am. Chem. Soc. 1948; 70: 320
      Crossref
    • 1g Horning EC, Stromberg VL, Lloyd HA. J. Am. Chem. Soc. 1952; 74: 5153
      Crossref
    • 1h Siddiqui MA, Snieckus V. Tetrahedron Lett. 1988; 29: 5463
      Crossref
    • 1i Banwell MG, Lupton DW, Ma X, Renner J, Sydnes MO. Org. Lett. 2004; 6: 2741
      CrossrefPubMed
    • 1j Bernini R, Cacchi S, Fabrizi G, Sferrazza A. Synthesis 2008; 729
      Artikel in Thieme Connect
    • 1k Dubost E, Magnelli R, Cailly T, Fabis F. Tetrahedron 2010; 66: 5008
      Crossref
    • 2a Thomas CJ, Wolak MA, Birge RR, Lees WJ. J. Org. Chem. 2001; 66: 1914
      CrossrefPubMed
    • 2b Coldham I, Dobson BC, Fletcher SR, Franklin AI. Eur. J. Org. Chem. 2007; 2676
    • 3a Olah GA. Friedel–Crafts Chemistry . Wiley/Interscience; New York: 1973
      CrossrefGoogle Scholar
    • 3b Ketcha DM, Gribble GW. J. Org. Chem. 1985; 50: 5451
      Crossref
    • 3c Wenkert E, Moeller PD. R, Piettre SR, McPhail AT. J. Org. Chem. 1988; 53: 3170
      Crossref
    • 3d Okauchi T, Itonaga M, Minami T, Owa T, Kitoh K, Yoshino H. Org. Lett. 2000; 2: 1485
      CrossrefPubMed
    • 3e Ottoni O, Neder AV. F, Dias AK. B, Cruz RP. A, Aquino LB. Org. Lett. 2001; 3: 1005
      CrossrefPubMed
    • 3f Katritzky AR, Suzuki K, Singh SK, He H.-Y. J. Org. Chem. 2003; 68: 5720
      CrossrefPubMed
    • 4a Sundberg RJ. The Chemistry of Indoles . Academic Press; New York: 1970
      Google Scholar
    • 4b Powers JC. J. Org. Chem. 1965; 30: 2534
      Crossref
    • 4c Seemann F, Wiskott E, Niklaus P, Troxler F. Helv. Chim. Acta 1971; 54: 2411
      Crossref
  • 5 Bergman J, Venemalm L. Tetrahedron Lett. 1987; 28: 3741
    Crossref
    • 6a Wu W, Su W. J. Am. Chem. Soc. 2011; 133: 11924
      CrossrefPubMed
    • 6b Li L.-T, Huang J, Li H.-Y, Wen L.-J, Wang P, Wang B. Chem. Commun. 2012; 48: 5187
      CrossrefPubMed
    • 6c Chen J, Liu B, Liu D, Liu S, Cheng J. Adv. Synth. Catal. 2012; 354: 2438
      Crossref
    • 7a Eyley SC, Giles RG, Heaney H. Tetrahedron Lett. 1985; 26: 4649
      Crossref
    • 7b Faul MM, Winneroski LL. Tetrahedron Lett. 1997; 38: 4749
      Crossref
  • 8 Yu L, Li P, Wang L. Chem. Commun. 2013; 49: 2368
    CrossrefPubMed
    • 9a Katritsky AR, Akutagawa K. Tetrahedron Lett. 1985; 26: 5935
      Crossref
    • 9b Mahboobi S, Sellmer A, Hocher H, Garhammer C, Pongratz H, Maier TT, Ciossek T, Beckers T. J. Med. Chem. 2007; 50: 4405
      CrossrefPubMed
    • 9c Brancale A, Silvestri R. Med. Res. Rev. 2007; 27: 209
      CrossrefPubMed
    • 9d Zhou B, Yang Y, Li Y. Chem. Commun. 2012; 48: 5163
      CrossrefPubMed
    • 9e Pan C, Jin H, Liu X, Cheng Y, Zhu C. Chem. Commun. 2013; 49: 2933
      Crossref
    • 9f Zhou W, Li P, Zhang Y, Wang L. Adv. Synth. Catal. 2013; 355: 2343
      Crossref
    • 10a Jia X, Zhang S, Wang W, Luo F, Cheng J. Org. Lett. 2009; 11: 3120
      CrossrefPubMed
    • 10b Li C, Wang L, Li P, Zhou W. Chem. Eur. J. 2011; 17: 10208
      CrossrefPubMed
    • 10c Chan C.-W, Zhou Z, Yu W.-Y. Adv. Synth. Catal. 2011; 353: 2999
      Crossref
    • 10d Szabo F, Daru J, Simko D, Nagy TZ, Stirling A, Novak Z. Adv. Synth. Catal. 2013; 355: 685
      Crossref
    • 10e Zhang Q, Li C, Yang F, Li J, Wu Y. Tetrahedron 2013; 69: 320
      Crossref
    • 11a Basle O, Bidange J, Shuai Q, Li C.-J. Adv. Synth. Catal. 2010; 352: 1145
      Crossref
    • 11b Jia X, Zhang S, Wang W, Luo F, Cheng J. Org. Lett. 2009; 11: 3120
      CrossrefPubMed
    • 11c Wu Y, Li B, Mao F, Li X, Kwong FY. Org. Lett. 2011; 13: 3258
      CrossrefPubMed
    • 11d Xiao F, Shuai Q, Zhao F, Basle Q, Deng G, Li C.-J. Org. Lett. 2011; 13: 1614
      CrossrefPubMed
    • 11e Correia CA, Yang L, Li C.-J. Org. Lett. 2011; 13: 4581
      CrossrefPubMed
    • 11f Fang P, Li M, Ge H. J. Am. Chem. Soc. 2010; 132: 11898
      CrossrefPubMed
    • 12a Guin S, Rout KS, Banerjee A, Nandi S, Patel BK. Org. Lett. 2012; 14: 5295
    • 12b Yin Z, Sun P. J. Org. Chem. 2012; 77: 11339
      CrossrefPubMed
  • 13 Jiang T.-S, Wang G.-W. Org. Lett. 2013; 15: 788
    CrossrefPubMed
    • 14a D’Angelo ND, Peterson JJ, Booker SK, Fellows I, Dominguez C, Hungate R, Reidera PJ, Kima T.-S. Tetrahedron Lett. 2006; 47: 5045
      Crossref
    • 14b Babu SG, Karvembu R. Tetrahedron Lett. 2013; 54: 1677
      Crossref
    • 15a Liu Y, Bai Y, Zhang J, Li Y, Jiao J, Qi X. Eur. J. Org. Chem. 2007; 6084
    • 15b Delvos LB, Begouin J.-M, Gosmini C. Synlett 2011; 2325
      Artikel in Thieme Connect
    • 15c Heo Y, Hyun D, Kumar MR, Jung HM, Lee S. Tetrahedron Lett. 2012; 53: 6657
      Crossref
    • 16a Gu S, Chen C, Chen W. J. Org. Chem. 2009; 74: 7203
      CrossrefPubMed
    • 16b Kakiuchi F, Kochi T, Mutsutani H, Kobayashi N, Urano S, Sato M, Nishiyama S, Tanabe T. J. Am. Chem. Soc. 2009; 131: 11310
      CrossrefPubMed
    • 16c Song B, Zheng X, Mo J, Xu B. Adv. Synth. Catal. 2010; 352: 329
      Crossref
    • 16d Zheng X, Song B, Li G, Liu B, Deng H, Xu B. Tetrahedron Lett. 2010; 51: 6641
      Crossref
    • 16e Xu S, Huang X, Hong X, Xu B. Org. Lett. 2012; 14: 4614
      CrossrefPubMed
    • 16f Zhang L, Xue X, Xu C, Pan Y, Zhang G, Xu L, Li H, Shi Z. ChemCatChem 2014; 6: 3069
      Crossref
    • 16g Shi J, Zhao G, Wang X, Xu HE, Yi W. Org. Biomol. Chem. 2014; 12: 6831
      CrossrefPubMed
    • 16h Ackermann L. J. Org. Chem. 2014; 79: 8948
      CrossrefPubMed
    • 16i Gong B, Shi J, Wang X, Yan Y, Li Q, Meng Y, Xu HE, Yi W. Adv. Synth. Catal. 2014; 356: 137
      Crossref
    • 16j Punji B, Song W, Shevchenko GA, Ackermann L. Chem. Eur. J. 2013; 19: 10605
      CrossrefPubMed
    • 16k Du J, Zhou B, Yang Y, Li Y. Chem. Asian J. 2013; 8: 1386
      CrossrefPubMed
  • 17 General Procedure: To a 25-mL sealed tube were added indole (0.3 mmol), aldehyde (0.45 mmol), Pd(OAc)2 (6.72 mg, 10 mmol%), anhydrous TBHP (ca. 5 M in decane, 4 equiv), and EtOAc (2.0 mL). The tube was capped and stirred under N2 at 125 °C for 24 h. The reaction mixture was cooled to room temperature and diluted with CH2Cl2, filtered through a short pad of Celite, and washed with brine and CH2Cl2. The combined organic extracts were dried over Na2SO4, concentrated in vacuo, and the resulting residue was purified by silica gel column chromatography to afford the desired product. [3-Methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl](phenyl)methanone (3as): Yield: 82%; white solid; mp 153–154 °C. 1H NMR (400 MHz, CDCl3): δ = 8.63 (d, J = 8.0 Hz, 1 H), 8.44 (d, J = 4.0 Hz, 2 H), 7.77 (d, J = 8.0 Hz, 2 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.48–7.40 (m, 2 H), 7.32 (q, J = 8.0 Hz, 3 H), 6.84 (t, J = 4.0 Hz, 1 H), 2.37 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 189.4, 157.5, 157.0, 139.2, 136.4, 133.2, 132.2, 130.2, 128.5, 128.3, 126.1, 122.5, 121.7, 120.1, 116.1, 115.2, 9.3; HRMS: m/z [M]+ calcd for C20H15N3O: 313.1207; found: 313.1210. [7-Methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl](phenyl)methanone (3at): Yield: 80%; yellow solid; mp 36–37 °C. 1H NMR (400 MHz, CDCl3): δ = 8.85 (d, J = 4.0 Hz, 2 H), 7.92 (d, J = 8.0 Hz, 2 H), 7.60–7.55 (m, 2 H), 7.48–7.45 (m, 2 H), 7.39 (t, J = 4.0 Hz, 1 H), 7.20 (s, 1 H), 7.13–7.11 (m, 2 H), 1.96 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 187.0, 159.7, 158.1, 138.3, 138.2, 136.0, 132.4, 129.6, 129.2, 128.2, 127.2, 122.4, 121.9, 121.1, 120.1, 116.4, 19.3. HRMS: m/z [M]+ calcd for C20H15N3O: 313.1207; found: 313.1210. (4-Methoxyphenyl)[1-(pyrimidin-2-yl)-1H-indol-2-yl]methanone (3au): Yield: 76%; white solid; mp 39–40 °C. 1H NMR (400 MHz, CDCl3): δ = 8.61 (d, J = 4.0 Hz, 2 H), 8.39 (d, J = 8.0 Hz, 1 H), 7.97 (d, J = 8.0 Hz, 2 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.41 (t, J = 8.0 Hz, 1 H), 7.27 (t, J = 8.0 Hz, 1 H), 7.07 (s, 1 H), 7.02 (t, J = 4.0 Hz, 1 H), 6.91 (d, J = 8.0 Hz, 2 H), 3.83 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 186.4, 163.3, 157.9, 157.2, 138.0, 137.2, 131.8, 130.7, 127.9, 126.1, 122.6, 122.2, 117.3, 114.5, 114.1, 113.5, 55.4; HRMS: m/z [M]+ calcd for C20H15N3O2: 329.1152; found: 329.1159. N-{4-[1-(Pyrimidin-2-yl)-1H-indole-2-carbonyl]phenyl}acetamide (3av): Yield: 67%; yellow solid; mp 138–139 °C. 1H NMR (400 MHz, CDCl3): δ = 9.11 (s, 1 H), 8.56 (d, J = 4.0 Hz, 2 H), 8.37 (d, J = 8.0 Hz, 1 H), 7.89 (d, J = 8.0 Hz, 2 H), 7.68–7.61 (m, 3 H), 7.41 (t, J = 8.0 Hz, 1 H), 7.26 (t, J = 8.0 Hz, 1 H), 7.07 (s, 1 H), 6.99 (t, J = 4.0 Hz, 1 H), 2.09 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 186.8, 169.4, 157.8, 157.0, 142.9, 138.0, 136.9, 132.7, 130.7, 127.8, 126.4, 122.7, 122.3, 118.7, 117.3, 115.1, 114.1, 24.28; HRMS: m/z [M]+ calcd for C21H16N4O2: 356.1273; found: 356.1268.
  • 18 Samanta S, Adak L, Jana R, Mostafa G, Tuononen HM, Ranu BC, Goswami S. Inorg. Chem. 2008; 47: 11062
    CrossrefPubMed
  • 19 Wang S, Yang Z, Liu J, Xie K, Wang A, Chen X, Tan Z. Chem. Commun. 2012; 48: 9924
    CrossrefPubMed
  • 20 Ackermann L, Lygin AV. Org. Lett. 2011; 13: 3332
    CrossrefPubMed
  • 21 Chan C.-W, Zhou Z, Chan AS. C, Yu W.-Y. Org. Lett. 2010; 12: 2010
    • 22a Deprez NR, Sanford MS. J. Am. Chem. Soc. 2009; 131: 11234
      CrossrefPubMed
    • 22b Racowski JM, Dick AR, Sanford MS. J. Am. Chem. Soc. 2009; 131: 10974
      CrossrefPubMed
    • 23a Powers DC, Ritter T. Nat. Chem. 2009; 1: 302
      CrossrefPubMed
    • 23b Powers DC, Geibel MA. L, Klein JE. M. N, Ritter T. J. Am. Chem. Soc. 2009; 131: 1705