A Metal-Free Three-Component Reaction for the Regioselective Synthesis of 1,4,5-Trisubstituted 1,2,3-Triazoles†
Dr. Joice Thomas
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Search for more papers by this authorDr. Jubi John
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Search for more papers by this authorNikita Parekh
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Search for more papers by this authorCorresponding Author
Prof. Dr. Wim Dehaen
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)Search for more papers by this authorDr. Joice Thomas
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Search for more papers by this authorDr. Jubi John
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Search for more papers by this authorNikita Parekh
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Search for more papers by this authorCorresponding Author
Prof. Dr. Wim Dehaen
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven (Belgium)Search for more papers by this authorWe thank the University of Leuven and the FWO-Vlaanderen for financial support. The Erasmus Exchange program “Experts II” is acknowledged for a fellowship to N.P.
Abstract
A metal-free three-component reaction to synthesize 1,4,5-trisubstituted 1,2,3-triazoles from readily available building blocks, such as aldehydes, nitroalkanes, and organic azides, is described. The process is enabled by an organocatalyzed Knoevenagel condensation of the formyl group with the nitro compound, which is followed by the 1,3-dipolar cycloaddition of the azide to the activated alkene. The reaction features an excellent substrate scope, and the products are obtained with high yield and regioselectivity. This method can be utilized for the synthesis of fused triazole heterocycles and materials with several triazole moieties.
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References
- 1For selected reviews on the application of 1,2,3-triazoles, see:
- 1a“Special issue on click chemistry”, Chem. Soc. Rev. 2010, 39, 1221–1408;
- 1bT. Muller, S. Bräse, Angew. Chem. 2011, 123, 12046–12047; Angew. Chem. Int. Ed. 2011, 50, 11844–11845;
- 1cC. Chu, R. Liu, Chem. Soc. Rev. 2011, 40, 2177–2188;
- 1dY. H. Lau, P. J. Rutledge, M. Watkinson, M. H. Todd, Chem. Soc. Rev. 2011, 40, 2848–2866;
- 1eD. Astruc, L. Liang, A. Rapakousiou, J. Ruiz, Acc. Chem. Res. 2012, 45, 630–640.
- 2
- 2aR. Alvarez, S. Velazquez, A. San-Felix, S. Aquaro, E. De Clercq, C.-F. Perno, A. Karlsson, J. Balzarini, M. J. Camarasa, J. Med. Chem. 1994, 37, 4185–4194;
- 2bR. S. Bohacek, C. McMartin, W. C. Guida, Med. Res. Rev. 1996, 16, 3–50;
10.1002/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.0.CO;2-6 CAS PubMed Web of Science® Google Scholar
- 2cM. J. Soltis, H. J. Yeh, K. A. Cole, N. Whittaker, R. P. Wersto, E. C. Kohn, Drug Metab. Dispos. 1996, 24, 799–806;
- 2dR. Kharb, P. C. Sharma, M. S. Yar, J. Enzyme Inhib. Med. Chem. 2011, 26, 1–21;
- 2eC. Sheng, W. Zhang, Curr. Med. Chem. 2011, 18, 733–766;
- 2fS. G. Agalave, S. R. Maujan, V. S. Pore, Chem. Asian J. 2011, 6, 2696–2718;
- 2gP. Thirumurugan, D. Matosiuk, K. Jozwiak, Chem. Rev. 2013, 113, 4905–4979.
- 3
- 3aV. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem. 2002, 114, 2708–2711;
10.1002/1521-3757(20020715)114:14<2708::AID-ANGE2708>3.0.CO;2-0 Google ScholarAngew. Chem. Int. Ed. 2002, 41, 2596–2599;10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4 CAS PubMed Web of Science® Google Scholar
- 3bC. W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057–3064;
- 3cP. Appukkuttan, W. Dehaen, V. V. Fokin, E. Van der Eycken, Org. Lett. 2004, 6, 4223–4225;
- 3dM. Meldal, C. W. Tornøe, Chem. Rev. 2008, 108, 2952–3015.
- 4
- 4aL. Zhang, X. G. Chen, P. Xue, H. H. Y. Sun, I. D. Williams, K. B. Sharpless, V. V. Fokin, G. C. Jia, J. Am. Chem. Soc. 2005, 127, 15998–15999;
- 4bL. K. Rasmussen, B. C. Boren, V. V. Fokin, Org. Lett. 2007, 9, 5337–5339.
- 5
- 5aL. M. Gaetke, C. K. Chow, Toxicology 2003, 189, 147–163;
- 5bA. J. Link, D. A. Tirrell, J. Am. Chem. Soc. 2003, 125, 11164–11165;
- 5cA. J. Link, M. K. S. Vink, N. J. Agard, J. A. Prescher, C. R. Bertozzi, D. A. Tirrell, Proc. Natl. Acad. Sci. USA 2006, 103, 10180–10185;
- 5dJ. A. Johnson, J. M. Baskin, C. R. Bertozzi, J. T. Koberstein, N. J. Turro, Chem. Commun. 2008, 3064–3066.
- 6For examples of organocatalytic [3+2] cycloaddition reactions, see:
- 6aD. B. Ramachary, K. Ramakumar, V. V. Narayana, Chem. Eur. J. 2008, 14, 9143–9147;
- 6bL. J. T. Danence, Y. Gao, M. Li, Y. Huang, J. Wang, Chem. Eur. J. 2011, 17, 3584–3587;
- 6cM. Belkheira, D. E. Abed, J.-M. Pons, C. Bressy, Chem. Eur. J. 2011, 17, 12917–12921;
- 6dL. Wang, S. Y. Peng, L. J. T. Danence, Y. Gao, J. Wang, Chem. Eur. J. 2012, 18, 6088–6093;
- 6eN. Seus, L. C. Goncalves, A. M. Deobald, L. Savegnago, D. Alves, M. W. Paixao, Tetrahedron 2012, 68, 10456–10463;
- 6fD. K. J. Yeung, T. Gao, J. Huang, S. Sun, H. Guo, J. Wang, Green Chem. 2013, 15, 2384–2388;
- 6gW. Li, Q. Jia, Z. Du, J. Wang, Chem. Commun. 2013, 49, 10187–10189;
- 6hD. B. Ramachary, A. B. Shashank, Chem. Eur. J. 2013, 19, 13175–13181;
- 6iN. Seus, B. Goldani, E. J. Lenardão, L. Savegnago, M. W. Paixão, D. Alves, Eur. J. Org. Chem. 2014, 1059–1065.
- 7A. Dömling, W. Wang, K. Wang, Chem. Rev. 2012, 112, 3083–3135.
- 8
- 8aJ. C. Piet, G. Le Hetet, P. Cailleux, H. Benhaoua, R. Carrie, Bull. Soc. Chim. Belg. 1996, 105, 33–44;
- 8bT. Wang, X.-C. Hu, X.-J. Huang, X.-S. Li, J.-W. Xie, J. Braz. Chem. Soc. 2012, 23, 1119–1123;
- 8cP. S. S. Lacerda, A. M. G. Silva, A. C. Tome, M. G. P. M. S. Neves, A. M. S. Silva, J. A. S. Cavaleiro, A. L. Llamas-Saiz, Angew. Chem. 2006, 118, 5613–5617;
10.1002/ange.200600747 Google ScholarAngew. Chem. Int. Ed. 2006, 45, 5487–5491.
- 9See the Supporting Information.
- 10
- 10aD. W. C. MacMillan, Nature 2008, 455, 304–308;
- 10bB. List, Angew. Chem. 2010, 122, 1774–1779;
10.1002/ange.200906900 Google ScholarAngew. Chem. Int. Ed. 2010, 49, 1730–1734;
- 10cS.-K. Xiang, B. Zhang, L.-H. Zhang, Y. Cui, N. Jiao, Chem. Commun. 2011, 47, 8097–8099;
- 10dP. Renzi, M. Bella, Chem. Commun. 2012, 48, 6881–6896.
- 11R. Ballini, S. Gabrielli, A. Palmieri, Eur. J. Org. Chem. 2014, DOI: 10.1002/ejoc.201301531.
- 12
- 12aP. T. Corbett, L. Vial, K. R. West, J.-L. Wietor, J. K. M. Sanders, S. Otto, Chem. Rev. 2006, 106, 3652;
- 12bJ.-M. Lehn, Chem. Soc. Rev. 2007, 36, 151;
- 12cJ. Thomas, G. Reekmans, P. Adriaensens, L. Van Meervelt, M. Smet, W. Maes, W. Dehaen, L. Dobrzanska, Angew. Chem. 2013, 125, 10427–10430; Angew. Chem. Int. Ed. 2013, 52, 10237–10240.
- 13
- 13aR. Huisgen, G. Szeimies, L. Möbius, Chem. Ber. 1967, 100, 2494–2507;
- 13bA. Padwa, in Comprehensive Organic Synthesis, Vol. 4 (Ed.: ), Pergamon, Oxford, 1991, pp. 1069–1109;
10.1016/B978-0-08-052349-1.00116-5 Google Scholar
- 13cJ. E. Hein, V. V. Fokin, Chem. Soc. Rev. 2010, 39, 1302–1315.
- 14
- 14aJ.-M. Kee, B. Villani, L. R. Carpenter, T. W. Muir, J. Am. Chem. Soc. 2010, 132, 14327–14329;
- 14bL. Li, G. Hao, A. Zhu, X. Fan, G. Zhang, L. Zhang, Chem. Eur. J. 2013, 19, 14403–14406.
- 15A referee suggested that this may be due to the cis arrangement of the H and Br substituents in the intermediary triazoline adduct.
- 16
- 16aB. H. M. Kuijpers, G. C. T. Dijkmans, S. Grootuys, P. J. L. M. Quaedflieg, R. H. Blaauw, F. L. van Delft, F. P. J. T. Rutjes, Synlett 2005, 3059–3062;
- 16bE. Rasolofonjatovo, S. Theeramunkong, A. Bouriaud, S. Kolodych, M. Chaumontet, F. Taran, Org. Lett. 2013, 15, 4698–4701.
- 17
- 17aS. W. Kwok, J. R. Fotsing, R. J. Fraser, V. O. Rodionov, V. V. Fokin, Org. Lett. 2010, 12, 4217–4219;
- 17bM. E. Meza-Aviña, M. K. Patel, C. B. Lee, T. J. Dietz, M. P. Croatt, Org. Lett. 2011, 13, 2984–2987;
- 17cF. Kloss, U. Köhn, B. O. Jahn, M. D. Hager, H. Görls, U. S. Schubert, Chem. Asian J. 2011, 6, 2816–2824;
- 17dG. Cheng, X. Zeng, J. Shen, X. Wang, X. Cui, Angew. Chem. 2013, 125, 13507–13510; Angew. Chem. Int. Ed. 2013, 52, 13265–13268;
- 17eA. Kayet, T. Pathak, J. Org. Chem. 2013, 78, 9865–9875.
- 18N. T. Nguyen, G. Mamardashvili, M. Gruzdev, N. Mamardashvili, W. Dehaen, Supramol. Chem. 2013, 25, 180–188.
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