synthesis and catalytic functionalization of biologically active indoles

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2 Objectives of this Work This thesis is presented as a cumulative collection of publications that have been submitted to or are already published in a range of international journals. The purpose of this summary is to depict the underlying reasons and ideas behind the journal articles and to clarify the relationship among them. The major aim of this work was the development of novel indole derivatives and their catalytic functionalization via palladium catalysis to biologically active 5-HT receptor ligands. Based on our experience in indole synthesis, our main focus was the titanium- and zinc-mediated synthesis to substituted indoles and their further functionalization. We presented for the first time the synthesis of electron-rich silyloxyindoles via titanium-catalyzed hydrohydrazination of propargyl alcohol derivatives in Synlett 2007 and the zinc-promoted hydrohydrazination of terminal alkynes to new indole derivatives in Angew. Chem. Int. Ed 2008. Furthermore we concentrated on their functionalization via palladium–catalyzed Buchwald-Hartwig amination reported in Tetrahedron Lett. 2007 and C-O crosscoupling reaction published in Synthesis 2007. We investigated a multitude of new complex targets based on the indole skeleton via cross-coupling reactions, sulfonylation and nucleophilic substitution to new 5-HT receptor ligands published in Org. Biomol. Chem. 2008 and in Eur. J. Org. Chem. 2008. Additionally, most of the synthesized compounds have been tested for it’s biologically activity. Additional achievements in catalytic hydroaminations which have been investigated during the synthesis of potential biologically active compounds are reported in Eur. J. Org. Chem. 2007, Tetrahedron 2008, ChemSusChem 2008, Org. Lett. 2008 and Tetrahedron Lett. 2008. They include improvements and explorations of methodologies for the synthesis and functionalization of indoles. 77
3 Publications 3.1 Titanium-Catalyzed Hydroamination of Propargyl Alcohol Derivatives: Synthesis of 3-Silyloxy-2-methylindoles via Hydrohydrazination Nicolle Schwarz, Karolin Alex, Iliyas Ali Sayyed, Vivek Khedkar, Annegret Tillack, Matthias Beller, Synlett 2007, 7, 1091-1095. Contributions: In this paper, I contributed to a significant amount of the argumentation and the synthetic work. I performed all catalytic investigations in Table 1 and the synthesis of compounds 4a, 4b, 4c and 4d. My contribution as coauthor of this paper is approximately 50%. 78
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Leibniz-Institut für Katalyse e. V
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Für meine Eltern Siegfried und Ker
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Mein besonderer Dank gilt Dr. Anneg
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Table of Contents Preface .........
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List of Abbreviations Ac Acetyl aq
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Preface The search for drugs is an
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1 Palladium-catalyzed Coupling Reac
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FULL PAPER DOI: 10.1002/ejoc.200700
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Synthesis of Indole-2,3-dicarboxyla
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3 Publications 132 3.8 Selective Re
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8 7 N R N R OH CO2Et CO2Et OH indol
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mixture was stirred at 78 C for 3 m
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3.89 (s, 2H, H-10), 4.27 (s, 2H, H-
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DOI: 10.1002/cssc.200700160 General
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Zn-Catalyzed Hydroamination of Term
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Zn-Catalyzed Hydroamination of Term
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3 Publications 146 3.10 Zn-Catalyze
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Over the past years, we investigate
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3 Publications 150 3.11 First Synth
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4608 K. Alex et al. / Tetrahedron L
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Publikationen 1 Titanium-Catalyzed
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