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

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
• 2a Morris SA, Anderson RJ. Tetrahedron 1990; 46: 715
• 2b Veluri R, Oka I, Wagner-Döbler I, Laatsch H. J. Nat. Prod. 2003; 66: 1520
• 2c Garbe TR, Kobayashi M, Shimizu N, Takesue N, Ozawa M, Yukawa H. J. Nat. Prod. 2000; 63: 596
• 3a Barbero M, Cadamuro S, Dughera S, Magistris C, Venturello P. Org. Biomol. Chem. 2011; 9: 8393
• 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
• 3d Nair V, Abhilash KG, Vidya N. Org. Lett. 2005; 7: 5857
• 3e Gibbs TJ. K, Tomkinson NC. O. Org. Biomol. Chem. 2005; 3: 4043
• 3f Liao B.-S, Chen J.-T, Liu S.-T. Synthesis 2007; 3125
• 3g Yadav JS, Subba Reddy BV, Gayathri KU, Meraj S, Prasad AR. Synthesis 2006; 4121
• 3h Nair V, Vidya N, Abhilash KG. Synthesis 2006; 3647
• 3i Zhang Z.-H, Yin L, Wang Y.-M. Synthesis 2005; 1949
• 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
• 3l Sharma GV. M, Reddy JJ, Lakshmi PS, Krishna PR. Tetrahedron Lett. 2004; 45: 7729
• 3m Farhanullah Sharon A, Maulik PR, Ram VJ. Tetrahedron Lett. 2004; 45: 5099
• 3n Mi X, Luo S, He J, Cheng J.-P. Tetrahedron Lett. 2004; 45: 4567
• 3o Bandgar BP, Shaikh KA. Tetrahedron Lett. 2003; 44: 1959
• 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
• 5 Yang J, Wang Z, Pan F, Li Y, Bao W. Org. Biomol. Chem. 2010; 8: 2975
• 6 Guo X, Pan S, Liu J, Li Z. J. Org. Chem. 2009; 74: 8848
• 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
• 8a Nobuta T, Hirashima S, Tada N, Miura T, Itoh A. Org. Lett. 2011; 13: 2576
• 8b Kanai N, Nakayama H, Tada N, Itoh A. Org. Lett. 2010; 12: 1948
• 8c Nobuta T, Hirashima S, Tada N, Miura T, Itoh A. Synlett 2010; 2335
• 8d Nakayama H, Itoh A. Tetrahedron Lett. 2007; 48: 1131
• 8e Nakayama H, Itoh A. Chem. Pharm. Bull. 2006; 54: 1620
• 9 Togo H, Iida S. Synlett 2006; 2159
• 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
• 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; R_f 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).�