Synthesis 2017; 49(17): 4025-4034
DOI: 10.1055/s-0036-1589036
paper
© Georg Thieme Verlag Stuttgart · New York

Brønsted Acid Catalyzed C3-Alkylation of 2-Indolylmethanols with Azlactones via an Umpolung Strategy

Yang Shen
,
Zi-Qi Zhu
,
Jin-Xi Liu
,
Lei Yu
,
Bai-Xiang Du*
,
Guang-Jian Mei*
,
Feng Shi*
We are grateful for the financial support from NSFC (21372002 and 21232007), PAPD, TAPP and the Undergraduate Student Project of Jiangsu Province.
Weitere Informationen

Publikationsverlauf

Received: 28. März 2017

Accepted after revision: 26. April 2017

Publikationsdatum:
20. Juni 2017 (online)


Abstract

An efficient method for the synthesis of C3-alkylated indoles has been established via Brønsted acid catalyzed alkylation of 2-indolylmethanols with azlactones. The reaction exhibits broad substrate scope and delivers high yields (22 examples, up to 99% yield). This approach not only provides a new strategy for the direct synthesis of C3-alkylated indoles, but also represents a rarely reported alkylation between indole motifs and electron-rich synthons at the C3 position. This protocol serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles from 2-indolylmethanols.

Supporting Information

 
  • References

  • 1 These authors contributed equally to the work.

    • For selected reviews, see:
    • 2a Humphrey GR. Kuethe JT. Chem. Rev. 2006; 106: 2875
    • 2b Bandini M. Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
    • 2c Kochanowska-Karamyan AJ. Hamann MT. Chem. Rev. 2010; 110: 4489
    • 2d Wang L. Chen Y.-Y. Xiao J. Asian J. Org. Chem. 2014; 3: 1036
  • 3 Usami Y. Yamaguchi J. Numata A. Heterocycles 2004; 63: 1123
  • 4 Liu J.-F. Jiang Z.-Y. Wang R.-R. Zeng Y.-T. Chen J.-J. Zhang X.-M. Ma Y.-B. Org. Lett. 2007; 9: 4127
    • 5a Pereira E. Youssef A. El-Ghozzi M. Avignant D. Bain J. Prudhomme M. Anizon F. Moreau P. Tetrahedron Lett. 2014; 55: 834
    • 5b Subba Reddy BV. Rajeswari N. Sarangapani M. Prashanthi Y. Ganji RJ. Addlagatta A. Bioorg. Med. Chem. Lett. 2012; 22: 2460
    • 5c Kamal A. Srikanth YV. V. Khan MN. A. Shaik TB. Ashraf M. Bioorg. Med. Chem. Lett. 2010; 20: 5229
    • 5d Paira P. Hazra A. Kumar S. Paira R. Sahu KB. Naskar S. Saha P. Mondal S. Maity A. Banerjee S. Mondal NB. Bioorg. Med. Chem. Lett. 2009; 19: 4786
    • 5e Wang Y. Tang X. Shao Z. Ren J. Liu D. Proksch P. Lin W. J. Antibiot. 2014; 67: 395

      For selected reviews, see:
    • 6a Cacchi S. Fabrizi G. Chem. Rev. 2005; 105: 2873
    • 6b Shiri M. Chem. Rev. 2012; 112: 3508
    • 6c Bandini M. Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
    • 6d Kochanowska-Karamyan AJ. Hamann MT. Chem. Rev. 2010; 110: 4489
    • 6e Zeng M. You S.-L. Synlett 2010; 1289
    • 6f Szatmari I. Sas J. Fulop F. Curr. Org. Chem. 2016; 20: 2038
  • 7 Lakhdar S. Westermaier M. Terrier F. Goumont R. Boubaker T. Ofial AR. Mayr H. J. Org. Chem. 2006; 71: 9088

    • For selected examples, see:
    • 8a Bandini M. Melloni A. Piccinelli F. Sinisi R. Tommasi S. Umani-Ronchi A. J. Am. Chem. Soc. 2006; 128: 1424
    • 8b Feng B. Pu X.-Y. Liu Z.-C. Xiao W.-J. Chen J.-R. Org. Chem. Front. 2016; 3: 1246
    • 8c Rueping M. Nachtsheim BJ. Moreth SA. Bolte M. Angew. Chem. Int. Ed. 2008; 47: 593
    • 8d Zeng M. Kang Q. Kang Q. He Q.-L. You S.-L. Adv. Synth. Catal. 2008; 350: 2169
    • 8e Dong H.-M. Lu H.-H. Lu L.-Q. Chen C.-B. Xiao W.-J. Adv. Synth. Catal. 2007; 349: 1597
    • 8f Kang Q. Zhao Z.-A. You S.-L. J. Am. Chem. Soc. 2007; 129: 1484
  • 9 Bandini M. Org. Biomol. Chem. 2013; 11: 5206

    • For related reviews, see:
    • 10a Klussmann M. Sureshkumar D. Synthesis 2011; 353
    • 10b Yeung SC. Dong VM. Chem. Rev. 2011; 111: 1215
    • 10c Girard SA. Knauber T. Li CJ. Angew. Chem. Int. Ed. 2014; 53: 74

      For related reviews, see:
    • 11a Palmieri A. Petrini M. Shaikh RR. Org. Biomol. Chem. 2010; 8: 1259
    • 11b Wang L. Chen Y. Xiao J. Asian J. Org. Chem. 2014; 3: 1036
    • 11c Zhu S. Xu L. Wang L. Xiao J. Youji Huaxue 2016; 36: 1229

    • For some examples from our group, see:
    • 11d Dai W. Lu H. Li X. Shi F. Tu S.-J. Chem. Eur. J. 2014; 20: 11382
    • 11e Tan W. Li X. Gong Y.-X. Ge M.-D. Shi F. Chem. Commun. 2014; 15901
    • 11f Tan W. Du B.-X. Li X. Zhu X. Shi F. Tu S.-J. J. Org. Chem. 2014; 79: 4635
    • 11g Shi F. Zhang H.-H. Sun X.-X. Liang J. Fan T. Tu S.-J. Chem. Eur. J. 2015; 21: 3465
    • 11h Jiang F. Zhang Y.-C. Yang X. Zhu Q.-N. Shi F. Synlett 2016; 27: 575

      For substitutions of 2-indolylmethanol, see:
    • 12a Fu T.-H. Bonaparte A. Martin S.-F. Tetrahedron Lett. 2009; 50: 3253
    • 12b Zhong X. Li Y. Han F.-S. Chem. Eur. J. 2012; 18: 9784
    • 12c Zhong X. Qi S. Li Y. Zhang J. Han F.-S. Tetrahedron 2015; 71: 3734
    • 12d Qi S. Liu C.-Y. Ding J.-Y. Han F.-S. Chem. Commun. 2014; 8605
    • 12e Liu C.-Y. Han F.-S. Chem. Commun. 2015; 11844

      For cyclizations of 2-indolylmethanol, see:
    • 13a Balczewski P. Bodzioch A. Rozycka-Sokolowska E. Marciniak B. Uznanski P. Chem. Eur. J. 2010; 16: 2392
    • 13b Granger B.-A. Jewett I.-T. Butler J.-D. Hua B. Knezevic C.-E. Parkinson E.-I. Hergenrother P.-J. Martin S.-F. J. Am. Chem. Soc. 2013; 135: 12984
    • 13c Yokosaka T. Nakayama H. Nemoto T. Hamada Y. Org. Lett. 2013; 15: 2978
    • 13d Yokosaka T. Kanehira T. Nakayama H. Nemoto T. Hamada Y. Tetrahedron 2014; 70: 2151
    • 13e Zhong X. Li Y. Zhang J. Zhang W.-X. Wang S.-X. Han F.-S. Chem. Commun. 2014; 11181
    • 13f Zhong X. Li Y. Zhang J. Han F.-S. Org. Lett. 2015; 17: 720
    • 13g Cao K.-S. Bian H.-X. Zheng W.-H. Org. Biomol. Chem. 2015; 13: 6449
    • 13h Bera K. Schneider C. Chem. Eur. J. 2016; 22: 7074
    • 13i Bera K. Schneider C. Org. Lett. 2016; 18: 5660
    • 14a Gong Y.-X. Wu Q. Zhang H.-H. Zhu Q.-N. Shi F. Org. Biomol. Chem. 2015; 13: 7993
    • 14b Sun X.-X. Zhang H.-H. Li G.-H. He Y.-Y. Shi F. Chem. Eur. J. 2016; 22: 17526
    • 14c Zhu Z.-Q. Shen Y. Sun X.-X. Tao J.-Y. Liu J.-X. Shi F. Adv. Synth. Catal. 2016; 358: 3797
    • 14d Li C. Zhang H.-H. Fan T. Shen Y. Wu Q. Shi F. Org. Biomol. Chem. 2016; 14: 6932
    • 14e He Y.-Y. Sun X.-X. Li G.-H. Mei G.-J. Shi F. J. Org. Chem. 2017; 82: 2462
    • 14f Zhang H.-H. Wang C.-S. Li C. Mei G.-J. Li Y. Shi F. Angew. Chem. Int. Ed. 2017; 56: 116
    • 14g Zhu Z.-Q. Shen Y. Liu J.-X. Tao J.-Y. Shi F. Org. Lett. 2017; 19: 1542

      For selected examples, see:
    • 16a Yu X.-Y. Chen J.-R. Wei Q. Cheng H.-G. Liu Z.-C. Xiao W.-J. Chem. Eur. J. 2016; 22: 6774
    • 16b Fisk JS. Tepe JJ. J. Am. Chem. Soc. 2007; 129: 3058
    • 16c Yamanaka M. Sakata K. Yoshioka K. Uraguchi D. Ooi T. J. Org. Chem. 2017; 82: 541
    • 16d Kikuchi J. Momiyama N. Terada M. Org. Lett. 2016; 18: 2521
  • 17 Zhang Y.-C. Zhu Q.-N. Yang X. Zhou L.-J. Shi F. J. Org. Chem. 2016; 81: 1681
  • 18 CCDC 1540646 (4aa) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.

    • For some reviews, see:
    • 19a Akiyama T. Chem. Rev. 2007; 107: 5744
    • 19b Terada M. Chem. Commun. 2008; 4097
    • 19c Terada M. Synthesis 2010; 1929
    • 19d Yu J. Shi F. Gong L.-Z. Acc. Chem. Res. 2011; 44: 1156
    • 19e Parmar D. Sugiono E. Raja S. Rueping M. Chem. Rev. 2014; 114: 9047
    • 19f Wu H. He Y.-P. Shi F. Synthesis 2015; 47: 1990