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Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 49, 2019 - Issue 24
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Synthetic Communications Reviews

Condensation of 2-methylindole with acetophenones: An unexpected formation of 2-arylanilines

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Pages 3442-3452 | Received 09 Jul 2019, Published online: 07 Oct 2019

References

  • (a) Sundberg, R. J. The Chemistry of Indoles, 1st ed., 1970. (b) Sundberg, R. J.; Katritzky, A. R.; Meth-Cohn, O.; Rees, C. S. Indoles; Academic Press: London, 1996.; (c) Shiri, M. Indoles in Multicomponent Processes (MCPs). Chem. Rev. 2012, 112, 3508–3549. DOI: 10.1021/cr2003954.
  • Recent reviews: (a) Chadha, N.; Silakari, O. Indoles as Therapeutics of Interest in Medicinal Chemistry: Bird’s Eye View. Eur. J. Med. Chem. 2017, 134, 159–184. DOI: 10.1016/j.ejmech.2017.04.003. (b) Kaushik, N. K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.; Verma, A. K.; Choi, E. H. Biomedical Importance of Indoles. Molecules 2013, 18, 6620–6662. DOI: 10.3390/molecules18066620.
  • Fischer, E. Ueber Das Methylketol. Justus Liebigs. Ann. Chem. 1887, 242, 372–383. DOI: 10.1002/jlac.18872420311.
  • (a) Noland, W. E.; Robinson, D. N. Synthesis of 3-Vinylindoles. J. Org. Chem. 1957, 22, 1134–1135. DOI: 10.1021/jo01360a031. (b) Barbero, M.; Dughera, S.; Alberti, S.; Ghigo, G. A Simple, Direct Synthesis of 3-Vinylindoles from the Carbocation-Catalysed Dehydrative Cross-Coupling of Ketones and Indoles. A Combined Experimental and Computational Study. Tetrahedron 2019, 75, 363–373. DOI: 10.1016/j.tet.2018.11.073.
  • An Example Of Preparative Use, Mattsson, C.; Svensson, P.; Boettcher, H.; Sonesson, C. Structure–Activity Relationship of 5-Chloro-2-Methyl-3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-Indole Analogues as 5-Ht6 Receptor Agonists. Eur. J. Med. Chem. 2013, 63, 578–588. DOI: 10.1016/j.ejmech.2013.03.006.
  • Scholtz, M. Uber Die Einwirkung Aliphatischer Ketone Auf Indol Und Seine Homologen Über Polymere Indole. Ber. Dtsch. Chem. Ges. 1913, 46, 1082–1089. DOI: 10.1002/cber.191304601141.
  • Examples of cascade processes via interception of vinylindoles formed in situ: (a) Chen, S.; Li, Y.; Ni, P.; Huang, H.; Deng, G.-J. Indole-to-Carbazole Strategy for the Synthesis of Substituted Carbazoles under Metal-Free Conditions. Org. Lett. 2016, 18, 5384–5387. DOI: 10.1021/acs.orglett.6b02762. (b) Noland, W. E.; Xia, G. M.; Gee, K. R.; Konkel, M. J.; Wahlstrom, M. J.; Condoluci, J. J.; Rieger, D. L. In Situ Vinylindole Synthesis. Diels-Alder Reactions with Maleic Anhydride and Maleic Acid to Give Tetrahydrocarbazoles and Carbazoles. Tetrahedron 1996, 52, 4555–4572. DOI: 10.1016/0040-4020(96)00152-4. (c) Noland, W. E.; Walhstrom, M. J.; Konkel, M. J.; Brigham, M. E.; Trowbridge, A. G.; Konkel, L. M. C.; Gourneau, R. P.; Scholten, C. A.; Lee, N. H.; Condoluci, J. J.; et al. In Situ Vinylindole Synthesis. Diels-Alder Reactions with Maleimides to Give Tetrahydrocarbazoles. J. Heterocycl. Chem. 1993, 30, 81–91. DOI: 10.1002/chin.199334162.
  • (a) Hong, C.; Firestone, G. L.; Bjeldanes, L. F. Bcl-2 Family-Mediated Apoptotic Effects of 3,3′-Diindolylmethane (DIM) in Human Breast Cancer. Cells. Biochem. Pharmacol. 2002, 63, 1085–1097. DOI: 10.1016/S0006-2952(02)00856-0. (b) Chakrabarty, M.; Basak, R.; Harigaya, Y. A Sojourn in the Synthesis and Bioactivity of Diindolylalkanes. Heterocycles 2001, 55, 2431–2447. (c) Rahimi, M.; Huang, K.-L.; Tang, C. K. 3,3′-Diindolylmethane (DIM) Inhibits the Growth and Invasion of Drug-Resistant Human Cancer Cells Expressing EGFR Mutants. Cancer Lett. 2010, 295, 59–68. DOI: 10.1016/j.canlet.2010.02.014. (d) Opperman, T. J.; Kwasny, S. M.; Li, J. B.; Lewis, M. A.; Aiello, D.; Williams, J. D.; Peet, N. P.; Moir, D. T.; Bowlin, T. L.; Long, E. C. DNA Targeting as a Likely Mechanism Underlying the Antibacterial Activity of Synthetic Bis-Indole Antibiotics. Antimicrob. Agents Chemother. 2016, 60, 7067–7076.
  • Bergman, J.; Norrby, P.-O.; Tilstam, U.; Venemalm, L. Structure Elucidation of Some Products Obtained by Acid-Catalyzed Condensation of Indole with Acetone. Tetrahedron 1989, 45, 5549–5564. DOI: 10.1016/S0040-4020(01)89501-6.
  • Noland, W. E.; Richards, C. G.; Desai, D. S.; Venkiteswaran, M. R. Cyclizative Condensations. III. Indole and 1-Methylindole with Methyl Ketones. J. Org. Chem. 1961, 26, 4254–4262. DOI: 10.1021/jo01069a019.
  • Banerji, J.; Asima Chatterjee, M.; Manna, S.; Pascard, C.; Prange, T.; N. Shoolery, J. Lewis Acid Induced Electrophilic Substitution of Indole. Part 3. Heterocycles 1981, 15, 325–336. DOI: 10.3987/S-1981-01-0325.
  • Chatterjee, A.; Manna, S.; Banerji, J.; Pascard, C.; Prangé, T.; Shoolery, J. N. Lewis-Acid-Induced Electrophilic Substitution in Indoles with Acetone. Part 2. J. Chem. Soc., Perkin Trans. 1980, 1, 553–555. DOI: 10.1039/P19800000553.
  • Noland, W. E.; Brown, C. D.; DeKruif, R. D.; Lanzatella, N. P.; Gao, S. M.; Zabronsky, A. E.; Tritch, K. J. Reactions of Indole with Acetophenones Affording Mixtures of 3,3-(1-Phenylethane-1,1-Diyl)Bis(1H-Indoles) and 1,2,3,4-Tetrahydro-3-(1H-Indol-3-yl)-1-Methyl-1,3-Diphenylcyclopent[b]Indoles. Syn. Comm. 2018, 48, 1755–1765. DOI: 10.1080/00397911.2018.1460760.
  • Angeles-Dunham, V. A.; Nickerson, D. M.; Ray, D. M.; Mattson, A. E. Nitrimines as Reagents for Metal‐Free Formal C(sp2)–C(sp2) Cross‐Coupling Reactions. Angew. Chem. 2014, 53, 14538–14541. DOI: 10.1002/ange.201408613.
  • Cao, L.-L.; Wang, D.-S.; Jiang, G.-F.; Zhou, Y.-G. An Efficient Route to 2,3-Disubstituted Indoles via Reductive Alkylation Using H2 as Reductant. Tetrahedron Lett. 2011, 52, 2837–2839. DOI: 10.1016/j.tetlet.2011.03.099.
  • Shao, Y.; Zeng, Y. M.; Ji, J. Y.; Sun, X. Q.; Yang, H. T.; Miao, C. B. The Cs2CO3–Catalyzed Reaction of 2-Oxindoles with Enones for the Preparation of Indolin-3-Ones and Their Further Transformation. J. Org. Chem. 2016, 81, 12443–12450. DOI: 10.1021/acs.joc.6b01993.
  • Noland, W. E.; Brown, C. D.; Zabronsky, A. E.; Tritch, K. J. Synthesis of 2-(9H-Carbazol-1-yl)Anilines from 2,3′-Biindolyl and Ketones. Tetrahedron 2018, 74, 2391–2404. DOI: 10.1016/j.tet.2018.03.066.
  • Formation of 1,3,5-triarylmethanes from acetophenones has been described: (a) Zhang, S. L.; Xue, Z. F.; Gao, Y. R.; Mao, S.; Wang, Y. Q. Triple Condensation of Aryl Methyl Ketones Catalyzed by Amine and Trifluoroacetic Acid: Straightforward Access to 1, 3, 5-Triarylbenzenes under Mild Conditions. Tetrahedron Lett. 2012, 53, 2436–2439. DOI: 10.1016/j.tetlet.2012.03.008. (b) Deng, K.; Huai, Q. Y.; Shen, Z. L.; Li, H. J.; Liu, C.; Wu, Y. C. Rearrangement of Dypnones to 1,3,5-Triarylbenzenes. Org. Lett. 2015, 17, 1473–1476. DOI: 10.1021/acs.orglett.5b00353.
  • Uruvakili, A.; Swamy, K. C. K. Gold Catalysed Transformation of 2-Arylindoles to Terphenyl Amines via 3-Dienyl Indoles and Brønsted Acid Promoted Formation of 2-Carboxyindoles to 3-Indenylindoles via 3-Allenylindoles. Org. Biomol. Chem. 2019, 17, 3275–3284. DOI: 10.1039/C9OB00232D.
  • Bandi, V.; Kavala, V.; Konala, A.; Hsu, C. H.; Villuri, B. K.; Reddy, S. R.; Lin, L.; Kuo, C. W.; Yao, C. F. Synthesis of Polysubstituted Cyclopentene and Cyclopenta[b]Carbazole Analogues from Unsymmetrical 4-Arylidene-3,6-Diarylhex-2-en-5-Ynal and Indole Derivatives via an Iodine Mediated Electrocyclization Reaction. J. Org. Chem. 2019, 84, 3036–3044. DOI: 10.1021/acs.joc.8b02168.
  • Krasnokutskaya, E. A.; Semenischeva, N. E.; Filimonov, V. D.; Knochel, P. A New, One-Step, Effective Protocol for the Iodination of Aromatic and Heterocyclic Compounds via Aprotic Diazotization of Amines. Synthesis 2007, 2007, 81–84. DOI: 10.1055/s-2006-958936.
  • Griffin, J. D.; Cavanaugh, C. L.; Nicewicz, D. A. Reversing the Regioselectivity of Halofunctionalization Reactions through Cooperative Photoredox and Copper Catalysis. Angew. Chem. Int. Ed. 2017, 56, 2097–2100. DOI: 10.1002/anie.201610722.

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