Download PDF
Synlett 2012; 23(20): 2975-2979
DOI: 10.1055/s-0032-1317508
letter
© Georg Thieme Verlag Stuttgart · New York

One-Pot Synthesis of Bisindolylmethanes from Benzyl Alcohols and Indoles Using Catalytic Iodine and Molecular Oxygen under Visible Light Irradiation

Tomoya Nobuta
Gifu Pharmaceutical University 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan   Fax: +81(58)2308108   Email: itoha@gifu-pu.ac.jp
,
Akitoshi Fujiya
Gifu Pharmaceutical University 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan   Fax: +81(58)2308108   Email: itoha@gifu-pu.ac.jp
,
Norihiro Tada
Gifu Pharmaceutical University 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan   Fax: +81(58)2308108   Email: itoha@gifu-pu.ac.jp
,
Tsuyoshi Miura
Gifu Pharmaceutical University 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan   Fax: +81(58)2308108   Email: itoha@gifu-pu.ac.jp
,
Akichika Itoh*
Gifu Pharmaceutical University 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan   Fax: +81(58)2308108   Email: itoha@gifu-pu.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 05 September 2012

Accepted: 28 September 2012

Publication Date:
23 November 2012 (online)

    Permissions and Reprints All articles of this category


Abstract

Bisindolylmethanes can be directly synthesized from benzyl alcohol and indole in up to 86% yield using molecular oxygen, visible light, and catalytic iodine, which serves as both an oxidant and a Lewis acid.

Key words

photooxidation - iodine - molecular oxygen - bisindolylmethane - benzyl alcohol
 

  • References and Notes

  • 1 Sundberg RJ. The Chemistry of Indoles . Academic Press; New York: 1970
    Google Scholar
    • 2a Morris SA, Anderson RJ. Tetrahedron 1990; 46: 715
      Crossref
    • 2b Veluri R, Oka I, Wagner-Döbler I, Laatsch H. J. Nat. Prod. 2003; 66: 1520
      Crossref
    • 2c Garbe TR, Kobayashi M, Shimizu N, Takesue N, Ozawa M, Yukawa H. J. Nat. Prod. 2000; 63: 596
      CrossrefPubMed
    • 3a Barbero M, Cadamuro S, Dughera S, Magistris C, Venturello P. Org. Biomol. Chem. 2011; 9: 8393
      CrossrefPubMed
    • 3b Karam A, Alonso JC, Gerganova TI, Ferreira P, Bion N, Barrault J, Jérôme F. Chem. Commun. 2009; 7000
    • 3c Podder S, Choudhury J, Roy UK, Roy S. J. Org. Chem. 2007; 72: 3100
      CrossrefPubMed
    • 3d Nair V, Abhilash KG, Vidya N. Org. Lett. 2005; 7: 5857
      Crossref
    • 3e Gibbs TJ. K, Tomkinson NC. O. Org. Biomol. Chem. 2005; 3: 4043
      Crossref
    • 3f Liao B.-S, Chen J.-T, Liu S.-T. Synthesis 2007; 3125
      Article in Thieme Connect
    • 3g Yadav JS, Subba Reddy BV, Gayathri KU, Meraj S, Prasad AR. Synthesis 2006; 4121
      Article in Thieme Connect
    • 3h Nair V, Vidya N, Abhilash KG. Synthesis 2006; 3647
      Article in Thieme Connect
    • 3i Zhang Z.-H, Yin L, Wang Y.-M. Synthesis 2005; 1949
      Article in Thieme Connect
    • 3j Ji S.-J, Zhou M.-F, Gu D.-G, Jiang Z.-Q, Loh T.-P. Eur. J. Org. Chem. 2004; 1584
    • 3k Bartoli G, Bosco M, Foglia G, Giuliani A, Marcantoni E, Sambri L. Synthesis 2004; 895
      Article in Thieme Connect
    • 3l Sharma GV. M, Reddy JJ, Lakshmi PS, Krishna PR. Tetrahedron Lett. 2004; 45: 7729
      Crossref
    • 3m Farhanullah Sharon A, Maulik PR, Ram VJ. Tetrahedron Lett. 2004; 45: 5099
      Crossref
    • 3n Mi X, Luo S, He J, Cheng J.-P. Tetrahedron Lett. 2004; 45: 4567
      Crossref
    • 3o Bandgar BP, Shaikh KA. Tetrahedron Lett. 2003; 44: 1959
      Crossref
    • 3p Yadav JS, Reddy BV. S, Murthy CV. S. R, Kumar GM, Madan C. Synthesis 2001; 783
  • 4 Ramachandiran K, Muralidharan D, Perumal PT. Tetrahedron Lett. 2011; 52: 3579
    Crossref
  • 5 Yang J, Wang Z, Pan F, Li Y, Bao W. Org. Biomol. Chem. 2010; 8: 2975
    Crossref
  • 6 Guo X, Pan S, Liu J, Li Z. J. Org. Chem. 2009; 74: 8848
    Crossref
    • 7a Khosropour AR, Mohammadpoor-Baltork I, Khodaei MM, Ghanbary P. Z. Naturforsch. B: Chem. Sci. 2007; 62: 537
    • 7b Whitney S, Grigg R, Derrick A, Keep A. Org. Lett. 2007; 9: 3299
      Crossref
    • 8a Nobuta T, Hirashima S, Tada N, Miura T, Itoh A. Org. Lett. 2011; 13: 2576
      Crossref
    • 8b Kanai N, Nakayama H, Tada N, Itoh A. Org. Lett. 2010; 12: 1948
      Crossref
    • 8c Nobuta T, Hirashima S, Tada N, Miura T, Itoh A. Synlett 2010; 2335
      Article in Thieme Connect
    • 8d Nakayama H, Itoh A. Tetrahedron Lett. 2007; 48: 1131
      Crossref
    • 8e Nakayama H, Itoh A. Chem. Pharm. Bull. 2006; 54: 1620
      Crossref
  • 9 Togo H, Iida S. Synlett 2006; 2159
    Article in Thieme Connect
  • 10 Gao M, Yang Y, Wu Y.-D, Deng C, Shu W.-M, Zhang D.-X, Cao L.-P, She N.-F, Wu A.-X. Org. Lett. 2010; 12: 4026
    Crossref
  • 11 General Procedure: A solution of 4-tert-butylbenzyl alcohol (1a; 0.3 mmol) and I2 (0.06 mmol) in anhyd EtOAc (5 mL) in a pyrex test tube, purged with an O2 balloon, was stirred and irradiated externally with four 22-W fluorescent lamps for 20 h. Indole (0.66 mmol) was added, and stirred for 10 min at r.t. The reaction mixture was washed with aq Na2S2O3 and concentrated in vacuo. Purification of the crude product by PTLC (hexane–EtOAc, 4:1) provided 3,3′-bis-(indolyl)-4-tert-butylphenylmethane (3aa; Rf 0.33; yield: 98.1 mg, 86%). 3,3′-Bis(indolyl)-4-tert-butylphenylmethane (3aa): 1H NMR (400 MHz, CDCl3): δ = 7.54 (br s, 2 H), 7.36 (d, J = 7.7 Hz, 2 H), 7.26–7.09 (m, 8 H), 6.98–6.94 (m, 2 H), 6.47 (s, 2 H), 5.80 (s, 1 H), 1.27 (s, 9 H). 3,3′-Bis(indolyl)phenylmethane (3ba): 1H NMR (400 MHz, CDCl3): δ = 7.44 (br s, 2 H), 7.34–7.08 (m, 11 H), 6.95 (t, J = 7.3 Hz, 2 H), 6.39 (s, 2 H), 5.80 (s, 1 H). 3,3′-Bis(indolyl)-4-methylphenylmethane (3ca): 1H NMR (400 MHz, CDCl3): δ = 7.41 (br s, 2 H), 7.34 (d, J = 8.2 Hz, 2 H), 7.17–7.05 (m, 6 H), 7.02 (d, J = 7.7 Hz, 2 H), 6.95 (t, J = 7.2 Hz, 2 H), 6.40 (s, 2 H), 5.78 (s, 1 H), 2.27 (s, 3 H). 3,3′-Bis(indolyl)-4-bromophenylmethane (3da): 1H NMR (400 MHz, CDCl3): δ = 7.50 (br s, 2 H), 7.24–7.02 (m, 10 H), 6.89 (m, 2 H), 6.34 (s, 2 H), 5.68 (s, 1 H). 3,3′-Bis(indolyl)-2-naphthylmethane (3ea): 1H NMR (500 MHz, DMSO-d 6): δ = 10.90 (br s, 2 H), 7.85–7.73 (m, 4 H), 7.57 (d, J = 8.6 Hz, 1 H), 7.40–7.35 (m, 6 H), 7.04 (t, J = 7.4 Hz, 2 H), 6.91–6.84 (m, 4 H), 6.05 (s, 1 H). 3,3′-Bis(indolyl)-4-chlorophenylmethane (3fa): 1H NMR (500 MHz, DMSO-d 6): δ = 10.87 (br s, 2 H), 7.36–6.83 (m, 14 H), 5.85 (s, 1 H). 3,3′-Bis(indolyl)-4-methoxyphenylmethane (3ga): 1H NMR (500 MHz, CDCl3): δ = 7.58 (br s, 2 H), 7.35–7.34 (m, 2 H), 7.21–7.09 (m, 6 H), 6.96 (t, J = 7.4 Hz, 2 H), 6.75 (d, J = 8.0 Hz, 2 H), 6.44 (s, 2 H), 5.77 (s, 1 H), 3.70 (s, 3 H). 3,3′-Bis(indolyl)-4-nitrophenylmethane (3ha): 1H NMR (500 MHz, DMSO-d 6): δ = 10.92 (br s, 2 H), 8.12 (d, J = 8.6 Hz, 2 H), 7.58 (d, J = 8.6 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.26 (d, J = 8.0 Hz, 2 H), 7.04–7.01 (m, 2 H), 6.88–6.84 (m, 4 H), 6.00 (s, 1 H). 2,2′-Bis[3-(carboxypropyl)indolyl]-4-methoxyphenylmethane (3gb): 1H NMR (400 MHz, DMSO-d 6): δ = 12.00 (br s, 2 H), 10.43 (br s, 2 H), 7.48 (d, J = 7.3 Hz, 2 H), 7.30 (d, J = 7.8 Hz, 2 H), 7.04–6.93 (m, 6 H), 6.87 (d, J = 8.7 Hz, 2 H), 5.97 (s, 1 H), 3.70 (s, 3 H), 2.72–2.69 (m, 4 H), 2.21 (t, J = 7.3 Hz, 4 H), 1.72–1.69 (m, 4 H). 2,2′-Bis[3-(carboxyethyl)indolyl]-4-nitrophenylmethane (3hc): 1H NMR (500 MHz, DMSO-d 6): δ = 12.09 (br s, 2 H), 10.78 (br s, 2 H), 8.20 (d, J = 8.6 Hz, 2 H), 7.50 (d, J = 7.4 Hz, 2 H), 7.35 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H), 7.04 (t, J = 7.4 Hz, 2 H), 6.98–6.95 (m, 2 H), 6.40 (s, 1 H), 3.01–2.88 (m, 4 H), 2.46–2.40 (m, 4 H).Bis(1-methylindol-3-yl)-4-tolylmethane (3cd): 1H NMR (500 MHz, CDCl3): δ = 7.37 (d, J = 8.0 Hz, 2 H), 7.24–7.14 (m, 6 H), 7.05 (d, J = 7.5 Hz, 2 H), 6.97–6.94 (m, 2 H), 6.50 (s, 2 H), 5.83 (s, 1 H), 3.58 (s, 6 H), 2.29 (s, 3 H).�5-(4-Methylphenyl)dipyrromethane (3ce): 1H NMR (500 MHz, CDCl3): δ = 7.91 (br s, 2 H), 7.13–7.09 (m, 4 H), 6.68–6.67 (m, 2 H), 6.16–6.14 (m, 2 H), 5.91 (s, 2 H), 5.43 (s, 1 H), 2.33 (s, 3 H).�