Modifications of carboxyindoles on solid phase
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Doctoral thesis (article-based)
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Date
2003-10-24
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Degree programme
Language
en
Pages
58
Series
Organic chemistry report, 3/2003
Abstract
Different solid phase modifications were studied in order to develop new and simple routes for pharmaceutically interesting highly substituted carboxyindoles. A convenient method for the preparation of 5-substituted 2-carboxyindoles and three novel direct functionalization methods for carboxyindoles were developed during this study. 5-Nitro-2-carboxyindole was synthesized easily in three steps from commercially available inexpensive 4-nitro-aniline. Through attachment of this template to solid phase followed by reduction, reductive amination, N-alkylation and cleavage, a small library of differently substituted carboxyindoles were obtained. Solid phase brominations were studied followed by palladium catalyzed Suzuki-coupling. This technology offers an efficient and selective method to introduce bromine and a new C-C-bond to 3-position of polymer bound 2-carboxyindoles. Formylation studies were also succesfull. By utilizing Vilsmeier formylation a new C-C-bond was obtained direcly and selectively at the 3-position of polymer bound 2-carboxyindoles. In solid phase metalation studies of 5-carboxyindoles a 4-position functionalization was achieved in 80 % regioselectivity. Despite the moderate regioselectivity it is obvious that ring lithiation can be adopted to solid phase.Description
Keywords
carboxyindoles, solid phase synthesis, direct functionalization, Vilsmeier formylation, lithiation, bromination
Other note
Parts
- Tois J., Franzén R., Aitio O., Huikko K. and Taskinen J., 2000. Preparation of 5-substituted 2-carboxyindoles on solid support. Tetrahedron Letters 41, No. 14, pages 2443-2446.
- Tois J., Franzén R., Aitio O., Laakso I., Huuskonen J. and Taskinen J., 2001. Solid-phase bromination and Suzuki coupling of 2-carboxyindoles. Combinatorial Chemistry & High Throughput Screening 4, No. 6, pages 521-524.
- Tois J., Franzén R., Aitio O., Laakso I. and Kylänlahti I., 2001. Vilsmeier formylation of 2-carboxyindoles and preparation of O-benzylhydroxyureas on solid phase. Journal of Combinatorial Chemistry 3, No. 6, pages 542-545.
- Tois J. and Koskinen A., 2003. Solid-phase lithiation of 5-carboxyindoles. Tetrahedron Letters 44, No. 10, pages 2093-2095.
- Tois J., Franzén R. and Koskinen A., 2003. Synthetic approaches towards indoles on solid phase recent advances and future directions. Tetrahedron 59, No. 29, pages 5395-5405.