CC BY ND NC 4.0 · SynOpen 2017; 01(01): 0097-0102
DOI: 10.1055/s-0036-1588559
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Copyright with the author

Triarylmethyl Cation Catalysis: A Tunable Lewis Acid Organo­catalyst for the Synthesis of Bisindolylmethanes

Nicholas G. Boekell, Dana J. Cerone, Maria M. Boucher, Phong K. Quach, Wilfried B. Tentchou Nganyak, Christine G. Reavis, Ifeanyi I. Okoh, Jordan O. A. Reid, Hayley E. Berg, Briana A. Chang, Cheyenne S. Brindle*
Acknowledgment is made to the Donors of the American Chemical Society Petroleum Research Fund for partial support of this research. We are grateful to the National Science Foundation (CHE-0619275 and CHE-0963165) for renovation and instrumentation grants that supported this research.
Further Information

Publication History

Received: 29 June 2017

Accepted after revision: 07 August 2017

Publication Date:
22 August 2017 (online)

Abstract

Triarylmethyl cations serve as tunable organocatalysts for the synthesis of bisindolylmethanes. The catalyst structure can be modified to increase or decrease reactivity as needed to match the requirements of the substrate. High yields are achieved for a variety of substrates by using these green catalysts. Catalyst tuning allows for the use of less reactive electrophiles by increasing the reactivity of the catalyst. Acid-sensitive products can be isolated under these mild reaction conditions.

Supporting Information

 
  • References and Notes

  • 1 Buckley BR. Annu. Rep. Prog. Chem., Sect. B: Org. Chem. 2013; 109: 189
  • 2 Bertelsen S. Jorgensen KA. Chem. Soc. Rev. 2009; 38: 2178
  • 3 Liu D. Chen EY.-X. Green Chem. 2014; 16: 964
  • 4 Shaikh IR. J. Catal. 2014; 1
  • 5 Enders D. Niemeier O. Henseler A. Chem. Rev. 2007; 107: 5606
  • 6 Flanigan DM. Romanov-Michailidis F. White NA. Rovis T. Chem. Rev. 2015; 115: 9307
  • 7 Liu J. Wang L. Synthesis 2017; 49: 960
  • 8 Khandelwal S. Tailor YK. Kumar M. Curr. Organocatal. 2016; 3: 176
  • 9 Mandalapu D. Synlett 2015; 26: 707
  • 10 Monaco MR. Pupo G. List B. Synlett 2016; 27: 1027
  • 11 Zhao R. Shi L. ChemCatChem 2014; 6: 3309
  • 12 Akiyama T. Mori K. Chem. Rev. 2015; 115: 9277
  • 13 Kobayashi S. Mukaiyama T. Chem. Lett. 1986; 15: 221
  • 14 Hayashi M. Mukaiyama T. Chem. Lett. 1987; 16: 289
  • 15 Denmark SE. Chen C.-T. Tetrahedron Lett. 1994; 35: 4327
  • 16 Naidu VR. Ni S. Franzén J. ChemCatChem 2015; 7: 1896
  • 17 Bah J. Franzén J. Chem. Eur. J. 2014; 20: 1066
  • 18 Bah J. Naidu VR. Teske J. Franzén J. Adv. Synth. Catal. 2015; 357: 148
  • 19 Veluru RN. Bah J. Franzén J. Eur. J. Org. Chem. 2015; 1834
  • 20 Ni S. Ramesh Naidu V. Franzén J. Eur. J. Org. Chem. 2016; 1708
  • 21 Horn M. Mayr H. J. Phys. Org. Chem. 2012; 25: 979
  • 22 Imran S. Taha M. Ismail NH. Khan KM. Naz F. Hussain M. Tauseef S. Molecules 2014; 19: 11722
  • 23 Praveen PJ. Parameswaran PS. Majik MS. Synthesis 2015; 47: 1827
  • 24 Xia M. Wang S. Yuan W. Synth. Commun. 2004; 34: 3175
  • 25 Xie Z.-B. Sun D.-Z. Jiang G.-F. Le Z.-G. Molecules 2014; 19: 19665
  • 26 General procedure for malachite green-catalyzed reactions: Indole (23.4 mg, 0.20 mmol), and malachite green (1.8 mg, 0.005 mmol) were added to a 1 dram vial equipped with a stir bar. Dichloromethane (0.5 mL, 0.2 M) was added, followed by the aldehyde (0.11 mmol; liquid aldehydes were directly injected, solid aldehydes were added as a solution in CH2Cl2) and the reaction was then heated to 35 °C. The reaction was stirred and the progress of the reaction was followed by TLC. The crude reaction was then purified by chromatography to isolate the product.3,3′-(Phenylmethylene)bis(1H-indole) (8a): The reaction time was 5 hours and a 15–25% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red foam (29.5 mg, 99% yield).3,3′-((4-Chlorophenyl)methylene)bis(1H-indole) (8b): The reaction time was 2 hours and a 15–35% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red foam (33.8 mg, 95% yield).4-(Di(1H-indol-3-yl)methyl)benzonitrile (8c): The reaction time was 30 minutes and a 15–45% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a pink foam (34.5 mg, 99.9% yield).3,3′-((4-(Trifluoromethyl)phenyl)methylene)bis(1H-indole) (8d): The reaction time was 30 minutes and a 15–25% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red foam (34.6 mg, 91% yield).3,3′-(Naphthalen-2-ylmethylene)bis(1H-indole) (8e): The reaction time was 1 hour and a 2–25% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red foam (34.7 mg, 94% yield).3,3′-((4-Methoxyphenyl)methylene)bis(1H-indole) (8f): The reaction time was 3 hours and a 15–40% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as an orange foam (33.7 mg, 96% yield).3,3′-((4-(Methylthio)phenyl)methylene)bis(1H-indole) (8g): The reaction time was 5 hours and a 10–35% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red oil (32.5 mg, 90% yield).3,3′-(p-Tolylmethylene)bis(1H-indole) (8h): The reaction time was 1 hour and a 15–25% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red foam (30.3 mg, 91% yield).3,3′-(m-Tolylmethylene)bis(1H-indole) (8i): The reaction time was 2 hours and a 15–35% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a peach foam (33.5 mg, 99.7% yield).3,3′-(o-Tolylmethylene)bis(1H-indole) (8j): The reaction time was 21 hours and a 15–30% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a white foam (34.1 mg, 99.4% yield).3,3′-((2-(Trifluoromethyl)phenyl)methylene)bis(1H-indole) (8k): The reaction time was 24 hours and a 20–40% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a white foam (36.7 mg, 95% yield). 4-(Di(1H-indol-3-yl)methyl)phenol (8m): The reaction time was 3 hours and a 25–80% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as an orange foam (30.2 mg, 91% yield). N-(4-(Di(1H-indol-3-yl)methyl)phenyl)acetamide (8n): The reaction time was 1 hour and a 20–100% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red-orange foam (36.6 mg, 96% yield). 3,3′-(3-Methylbutane-1,1-diyl)bis(1H-indole) (8o): The reaction time was 2 hours and a 15–35% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a light-brown foam (27.2 mg, 90% yield). 3,3′-(Phenylmethylene)bis(5-bromo-1H-indole) (8r): The reaction time was 45 minutes and a 5–45% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red-orange foam (82.0 mg, 87% yield).3,3′-(Phenylmethylene)bis(5-methoxy-1H-indole) (8s): The reaction time was 15 minutes and a 5–30% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a white solid (70.1 mg, 93% yield). Dimethyl 3,3′-(Phenylmethylene)bis(1H-indole-5-carboxylate) (8t): The reaction time was 1 hour and a 18–45% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a light-pink solid (74.0 mg, 87% yield).3,3′-(Phenylmethylene)bis(1-methyl-1H-indole) (8u): This reaction was done on a 0.4 mmol scale. The reaction time was 1 hour and a 2–10% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a pink foam (133.6 mg, 95% yield). 3,3′-(Phenylmethylene)bis(1-butyl-1H-indole) (8v): The reaction time was 15 minutes and a 5–20% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red foam (38.6 mg, 90% yield). 3,3′-(Phenylmethylene)bis(1-isopropyl-1H-indole) (8w): The reaction time was 45 minutes and a 2–12% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a red film (69.0 mg, 86% yield). 3,3′-(Phenylmethylene)bis(2-methyl-1H-indole) (8x): The reaction time was 30 minutes and the mixture was then diluted with methanol and washed with sodium bisulfite to remove excess benzaldehyde.26 Ethyl acetate: hexanes (1:1) was then added to extract the organic layer, which was then dried (MgSO4), filtered, and concentrated in vacuo to give the title compound as a pink foam (35.0 mg, 99% yield)
  • 27 Boucher MM. Furigay MH. Quach PK. Brindle CS. Org. Process Res. Dev. 2017; DOI: DOI: 10.1021/acs.oprd.7b00231.
  • 28 General Procedure for Reactions using Tri-p-methoxyphenylmethanol as Precatalyst: Tri-p-methoxyphenylmethanol (0.011 mmol) was added to a 1 dram vial equipped with a stir bar and a cap fitted with a septum. Dichloromethane (0.2 mL) was added, followed by tetrafluoroboric acid diethyl etherate complex (1.4 μL, 0.010 mmol) to give a bright red-orange color. Aldehyde (0.11 mmol) was then added by using a syringe, followed by indole (23.4 mg, 0.20 mmol) as a solution in dichloromethane (0.2 mL, and a 0.1 mL rinse). The reaction was stirred and the progress of the reaction was followed by TLC. The crude reaction was then purified by chromatography to isolate the product.3,3′-(2-Pyridinylmethylene)bis-(1H-indole) (8l): The reaction time was 16 hours and a 40–70% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a white amorphous solid (30.5 mg, 95% yield).3,3′-(2-Methylpropylidene)bis(1H-indole) (8p): The reaction time was 16 hours and a 10–25% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a white foam (28.9 mg, 99% yield). 3,3′-(Cyclohexane-1,1-diyl)bis(1H-indole) (8q): The reaction time was 16 hours and a 10–25% ethyl acetate/hexanes gradient was used to purify the crude reaction mixture to give the title compound as a white foam (30.8 mg, 98% yield)
  • 29 Guieu S. Rocha J. Silva AM. S. Tetrahedron Lett. 2013; 54: 2870