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Synlett 2017; 28(14): 1852-1856
DOI: 10.1055/s-0036-1588432
letter
© Georg Thieme Verlag Stuttgart · New York

Sc(OTf)3-Catalyzed Aza-Friedel–Crafts Reaction of Electron-Rich Arenes with Isatin-Derived Ketimines: Access to 3-Amino-3-Aryl-2-Oxindoles

Hongjie Gao
a   College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: xuxsh1970@126.com
,
Xiangsheng Xu*
a   College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. of China   Email: xuxsh1970@126.com
,
Jianfeng Xu  *
b   Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: jfxu@zstu.edu.cn
› Author AffiliationsWe gratefully acknowledge the National Natural Science Foundation of China (Grant No. 21602203), the Natural Science Foundation of Zhejiang Province (Grant No. LQ16B020001), and the Natural Science Foundation of Zhejiang Sci-Tech University (Grant No. 15062018-Y) for financial support.
Further Information

Publication History

Received: 21 March 2017

Accepted after revision: 30 April 2017

Publication Date:
31 May 2017 (online)

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Abstract

A Sc(OTf)3-catalyzed aza-Friedel–Crafts reaction of electron-rich arenes with isatin-derived ketimines is disclosed, providing biologically interesting 3-amino-3-aryl-2-oxindoles in moderate to good yields with broad substrate scope. This reaction can be easily scaled up, and the Boc protecting group could be readily removed under mild reaction conditions to afford the free amine.

Key words

Lewis acids - aza-Friedel–Crafts - electron-rich arenes - isatin-derived ketimines - 3-amino-3-aryl-2-oxindoles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1588432.
  • Supporting Information
 

  • References and Notes

    • 1a Peddibhotla S. Curr. Bioact. Compd. 2009; 5: 20
      Crossref
    • 1b Badillo JJ. Hanhan NV. Franz AK. Curr. Opin. Drug Discovery Dev. 2010; 13: 758
    • 1c Shen K. Liu X. Lin L. Feng X. Chem. Sci. 2012; 3: 327
      Crossref
    • 1d Hong L. Wang R. Adv. Synth. Catal. 2013; 355: 1023
      Crossref
    • 1e Bergman J. In Advances in Heterocyclic Chemistry . Vol. 117. Scriven EF. V. Ramsden CA. Elsevier; San Diego: 2015: 1
      Google Scholar
    • 1f Kaur M. Singh M. Chadha N. Silakari O. Eur. J. Med. Chem. 2016; 123: 858
      CrossrefPubMed
    • 2a Zhou F. Liu Y.-L. Zhou J. Adv. Synth. Catal. 2010; 352: 1381
      Crossref
    • 2b Chauhan P. Chimni SS. Tetrahedron: Asymmetry 2013; 24: 343
      Crossref
    • 2c Kaur J. Chimni SS. Mahajan S. Kumar A. RSC Adv. 2015; 5: 52481
      Crossref
    • 3a Bernard K. Bogliolo S. Ehrenfeld JB. J. Pharmacol. 2005; 144: 1037
    • 3b Shimazaki T. Iijima M. Chaki S. Eur. J. Pharmacol. 2006; 543: 63
      CrossrefPubMed
    • 3c Decaux G. Soupart A. Vassart G. Lancet 2008; 371: 1624
      CrossrefPubMed
    • 3d Oost T. Backfisch G. Bhowmik S. van Gaalen MM. Geneste H. Hornberger W. Lubisch W. Netz A. Unger L. Wernet W. Bioorg. Med. Chem. Lett. 2011; 21: 3828
      CrossrefPubMed
    • 4a Rottmann M. McNamara C. Yeung BS. K. Lee MC. S. Zou B. Russell B. Seitz P. Plouffe DM. Dharia NV. Tan J. Cohen SB. Spencer KR. Gonzalez-Paez G. Lakshiminarayana L. Goh A. Suwanarusk R. Jegla T. Schmitt EK. Beck H.-P. Brun R. Nosten F. Renia L. Dartois V. Keller TH. Fidock DA. Winzeler EA. Diagana TT. Science 2010; 329: 1175
      CrossrefPubMed
    • 4b Yeung BK. S. Zou B. Rottmann M. Lakshminarayana SB. Ang SH. Leong SY. Tan J. Wong J. Keller-Maerki S. Fischli C. Goh A. Schmitt EK. Krastel P. Francotte E. Kuhen K. Plouffe D. Henson K. Wagner T. Winzeler EA. Petersen F. Brun R. Dartois V. Diagana TT. Keller TH. J. Med. Chem. 2010; 53: 5155
      CrossrefPubMed
    • 5a Jia Y.-X. Hillgren JM. Watson EL. Marsden SP. Kündig EP. Chem. Commun. 2008; 4040
      PubMed
    • 5b Tolstoy P. Lee SX. Y. Sparr C. Ley SV. Org. Lett. 2012; 14: 4810
      CrossrefPubMed
    • 6a Bui T. Hernández-Torres G. Milite C. Barbas III CF. Org. Lett. 2010; 12: 5696
      CrossrefPubMed
    • 6b Zhou F. Ding M. Liu Y.-L. Wang C.-H. Ji C.-B. Zhang Y.-Y. Zhou J. Adv. Synth. Catal. 2011; 353: 2945
      Crossref
    • 6c Yang C. Liu Y. Yang J.-D. Li Y.-H. Li X. Chen J.-P. Org. Lett. 2016; 18: 1036
      CrossrefPubMed
    • 7a Lesma G. Landoni N. Pilati T. Sacchetti A. Silvani A. J. Org. Chem. 2009; 74: 4537
      CrossrefPubMed
    • 7b Jung HH. Buesking AW. Ellman JA. Org. Lett. 2011; 13: 3912
      CrossrefPubMed
    • 7c Peng J. Yan W. Wang D. Li P. Sun Q. Wang R. Chem. Commun. 2012; 48: 8003
      CrossrefPubMed
    • 7d Montesinos-Magraner M. Vila C. Cantón R. Blay G. Fernández I. Muñoz MC. Pedro JR. Angew. Chem. Int. Ed. 2015; 54: 6320
      CrossrefPubMed
    • 7e Montesinos-Magraner M. Vila C. Rendón-Patiño A. Blay G. Fernández I. Muñoz MC. Pedro JR. ACS Catal. 2016; 6: 2689
      Crossref
    • 7f He Q. Wu L. Kou X. Butt N. Yang G. Zhang W. Org. Lett. 2016; 18: 288
      CrossrefPubMed
    • 8a Schinzer D. Selectivities in Lewis Acid Promoted Reactions . Kluwer Academic Publishers; Dordrecht: 1989
      Google Scholar
    • 8b Yamamoto H. Lewis Acids in Organic Synthesis . Wiley-VCH; Weinheim: 2000
      Google Scholar

      For a recent review, see ref. 2c; for selected recent examples, see:
    • 9a Lv H. Tiwari B. Mo J. Xing C. Chi YR. Org. Lett. 2012; 14: 5412
      CrossrefPubMed
    • 9b Chen D. Xu MH. Chem. Commun. 2013; 49: 1327
      CrossrefPubMed
    • 9c Arai T. Matsumura E. Masu H. Org. Lett. 2014; 16: 2768
      CrossrefPubMed
    • 9d BeceÇo C. Chauhan P. Rembiak A. Wang A. Enders D. Adv. Synth. Catal. 2015; 357: 672
      Crossref
    • 9e Zhao H. -W. Li B. Pang H.-L. Tian T. Chen X.-Q. Song X.-Q. Meng W. Yang Z. Zhao Y.-D. Liu Y.-Y. Org. Lett. 2016; 18: 848
      CrossrefPubMed
    • 10a Xu J. Mou C. Zhu T. Song B.-A. Chi YR. Org. Lett. 2014; 16: 3272
      CrossrefPubMed
    • 10b Xu J. Yuan S. Miao M. Org. Lett. 2016; 18: 3822
      CrossrefPubMed
    • 10c Xu J. Yuan S. Peng J. Miao M. Chen Z. Ren H. Chem. Commun. 2017; 53: 3430
      CrossrefPubMed
  • 11 General Procedure for the Catalytic Synthesis of Products 3 To a dry 4 mL vial equipped with a magnetic stir bar, were added electron-rich arene 1 (0.15 mmol), isatin-derived ketamine 2 (0.1 mmol), 4 Å MS (100 mg, powder), Sc(OTf)3 (0.01 mmol), and anhydrous MeCN (1 mL). The tube was sealed with a septum, and the reaction mixture was stirred at r.t. for another 12 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was subjected to column chromatography using hexane–EtOAc = 4:1 as eluent to afford the desired product 3. tert-Butyl-[1-benzyl-2-oxo-3-(2,4,6-trimethoxyphenyl)indolin-3-yl]carbamate (3a) 41.4 mg, 82% yield, white solid, mp 164–165 °C. 1H NMR (500 MHz, CDCl3): δ = 7.52 (d, J = 7.5 Hz, 2 H), 7.36 (d, J = 7 Hz, 1 H), 7.32 (t, J = 7.5 Hz, 2 H), 7.26 (t, J = 6.5 Hz, 1 H), 7.09 (t, J = 7.5 Hz, 1 H), 6.87 (t, J = 7.5 Hz, 1 H), 6.65 (d, J = 7.5 Hz, 1 H), 6.13 (s, 2 H), 5.07 (br, 2 H), 3.73 (s, 3 H), 3.63 (br, 6 H), 1.31 (br, 9 H). 13C NMR (125 MHz, CDCl3): δ = 176.6, 160.5, 159.0, 153.6, 143.9, 136.8, 131.4, 128.4, 128.3, 127.7, 127.1, 123.4, 122.0, 108.7, 108.4, 93.1, 79.2, 62.6, 56.3, 55.2, 44.6, 28.3. ESI-HRMS: m/z calcd for C29H32N2O6Na+: 527.2158; found: 527.2167.
  • 12 For a similar product with sulfinyl as the protecting group prepared from Bi(OTf)3-catalyzed aza-Friedel–Crafts reaction of indoles with isatin-derived ketimines, see: Chen J.-P. Chen W.-W. Li Y. Xu M.-H. Org. Biomol. Chem. 2015; 13: 3363
    CrossrefPubMed
  • 13 Marques CS. Burke AJ. Eur. J. Org. Chem. 2016; 806