Brønsted Acid Catalyzed Synthesis of Unsymmetrical Arylbis(3-indolyl)-methanes

Abstract

Unsymmetrical arylbis(3-indolyl)methanes have been synthesized via a Brønsted acid catalyzed Friedel-Crafts alkylation of α-(3-indolyl)benzylamines with N-methylindole. With 5 mol% of the catalyst, the reaction proceeds smoothly under mild conditions, affording the unsymmetrical triarylmethanes in excellent yields (up to 98%).

Key words

Brønsted acids - Friedel-Crafts reaction - indole - unsymmetrical triarylmethane

References and Notes

• For reviews, see:
• 1a Duxbury DF. Chem. Rev.  1993,  93:  381 
• 1b Shchepinov MS. Korshun VA. Chem. Soc. Rev.  2003,  32:  170 
• 1c Nair V. Thomas S. Mathew SC. Abhilash KG. Tetrahedron  2006,  62:  6731 
• Selected recent examples:
• 2a Wang S.-Y. Ji S.-J. Synth. Commun.  2008,  38:  1291 
• 2b Khalafi-Nezhad A. Parhami A. Zare A. Zare ARM. Hasaninejad A. Panahi F. Synthesis  2008,  617 
• 2c Khodaei MM. Mohammadpoor-Baltork I. Memarian HR. Khosropour AR. Nikoofar K. Ghanbary P. J. Heterocycl. Chem.  2008,  45:  377 
• 2d Hosseini-Sarvari M. Synth. Commun.  2008,  38:  832 
• Selected examples:
• 3a Yadav JS. Reddy BVS. Murthy CVSR. Kumar GM. Madan C. Synthesis  2001,  783 
• 3b Ramesh C. Banerjee J. Pal R. Das B. Adv. Synth. Catal.  2003,  345:  557 
• 3c Nair V. Abhilash KG. Vidya N. Org. Lett.  2005,  7:  5857 
• 3d Podder S. Choudhury J. Roy UK. Roy S. J. Org. Chem.  2007,  72:  3100 
• 3e Wang Z. Sun X. Wu J. Tetrahedron  2008,  64:  5013 
• 3f Sun S. Wang M. Deng H. Liu Q. Synthesis  2008,  573 
• 3g Liu C.-R. Li M.-B. Yang C.-F. Tian S.-K. Chem. Commun.  2008,  1249 ; and references cited therein
• Selected examples:
• 4a Das SK. Panda SG. Tetrahedron Lett.  2005,  46:  3097 
• 4b Esquivias J. Gómez-Arrayás R. Carretero JC. Angew. Chem. Int. Ed.  2006,  45:  629 
• 4c Katritzky AR. Toader D. J. Org. Chem.  1997,  62:  4137 
• 4d Lin S. Lu X. J. Org. Chem.  2007,  72:  9757 
• 4e Yu J.-Y. Kuwano R. Org. Lett.  2008,  10:  973 
• 4f Li Z. Duan Z. Kang J. Wang H. Yu L. Wu Y. Tetrahedron  2008,  64:  1924 
• 4g Li G. Wang E. Chen H. Li H. Liu Y. Wang PG. Tetrahedron  2008,  64:  9033 
• 4h Alonso I. Esquivias J. Gómez-Arrayás R. Carretero JC. J. Org. Chem.  2008,  73:  6401 
• 4i Deb ML. Bhuyan PJ. Synthesis  2008,  2891 
• Reviews on chiral phosphoric acid catalysis:
• 5a Taylor MS. Jacobsen EN. Angew. Chem. Int. Ed.  2006,  45:  1520 
• 5b Akiyama T. Chem. Rev.  2007,  107:  5744 
• 5c Yu X. Wang W. Chem. Asian J.  2008,  3:  516 
• 5d Terada M. Chem. Commun.  2008,  4097 
• 6a Kang Q. Zhao Z.-A. You S.-L. J. Am. Chem. Soc.  2007,  129:  1484 
• 6b Wang Y.-Q. Song J. Hong R. Li H. Deng L. J. Am. Chem. Soc.  2006,  128:  8156 
• 6c Jia Y.-X. Xie J.-H. Duan H.-F. Wang L.-X. Zhou Q.-L. Org. Lett.  2006,  8:  1621 
• 6d Kang Q. Zheng X.-J. You S.-L. Chem. Eur. J.  2008,  14:  3539 
• For reviews, see:
• 7a Bosch J. Bennasar M.-L. Synlett  1995,  587 
• 7b Faulkner DJ. Nat. Prod. Rep.  2002,  19:  1 
• 7c Agarwal S. Caemmerer S. Filali S. Froehner W. Knoell J. Krahl MP. Reddy KR. Knoelker H.-J. Curr. Org. Chem.  2005,  9:  1601 
• 7d O’Connor SE. Maresh JJ. Nat. Prod. Rep.  2006,  23:  532 
• 7e For a recent example, see: Pouilhès A. Kouklovsky C. Langlois Y. Baltaze J.-P. Vispé S. Annereau J.-P. Barret J.-M. Kruczynski A. Bailly C. Bioorg. Med. Chem. Lett.  2008,  18:  1212 
• 8 Terada M. Sorimachi K. Uraguchi D. Synlett  2006,  133 

9

General Procedure for the Synthesis of the Unsymmetrical Arylbis(3-indolyl)methanes in Table 2 In a dry Schlenk tube, α-(3-indolyl)benzylamine 2 (0.20 mmol; see ref. 6 for the preparation) and phosphorodiamidic acid 1 (4.8 mg, 0.01 mmol) were dissolved in toluene (4 mL) under argon. N-Methylindole (39.3 mg, 0.30 mmol) was added and the solution was stirred at r.t. After the reaction was complete (monitored by TLC), sat. aq NaHCO₃ (3 mL) was added to quench the reaction. The mixture was extracted with EtOAc (10 mL). The organic layer was washed by brine (5 mL), separated, and dried over anhyd Na₂SO₄. The solvents were removed under reduced pressure, and the residue was purified by flash chromatography (EtOAc-PE, 1:8 to 1:5) to afford the product.

10

3-[(1-Methyl-1 H -indol-3-yl)(phenyl)methyl]-1 H -indole (Table 2, Entry 1)
Prepared according to the general procedure to provide the title compound as a white solid (94% yield) following silica gel chromatography (EtOAc-PE, 1:6).
Analytical Data
^¹H NMR (300 MHz, CDCl₃): δ = 3.65 (s, 3 H), 5.87 (s, 1 H), 6.49 (s, 1 H), 6.63 (s, 1 H), 6.69-7.02 (m, 2 H), 7.13-7.39 (m, 11 H), 7.82 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 32.6, 40.1, 109.1, 111.0, 118.0, 118.6, 119.1, 119.7, 119.9, 120.0, 121.4, 121.8, 123.6, 126.0, 127.4, 126.0, 126.9, 127.4, 128.1, 128.2, 128.6, 136.5, 137.3, 144.1. IR (film): 3410, 3053, 2923, 1605, 1456, 1418, 1371, 1329, 1154, 1092, 1011, 740, 703, 580 cm^-¹. HRMS (EI): m/z calcd for C₂₄H₂₀N₂: 336.1626; found: 336.1628.