synthesis and catalytic functionalization of biologically active indoles

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LETTER Synthesis of 3-Silyloxy-2-methylindoles 1095 (15) For the synthesis of 3-phenoxy- and 3-methoxyindoles, see: (a) Baccolini, G.; Dalpozzo, R.; Todesco, P. E. J. Chem. Soc., Perkin Trans. 1 1988, 971. (b) De Rosa, M.; Carbognani, L.; Febres, A. J. Org. Chem. 1981, 46, 2054. (c) For the synthesis of 2-methylcarboxylate-3-(tert-butyldimethylsilyloxy)indole, see: Malapel-Andrieu, B.; Mérour, J.-Y. Tetrahedron 1998, 54, 11079. (16) Kawashima, Y.; Amanuma, F.; Sato, M.; Okuyama, S.; Nakashima, Y.; Sota, K.; Moriguchi, I. J. Med. Chem. 1986, 29, 2284. (17) Gormemis, A. E.; Ha, T. S.; Im, I.; Jung, K.-Y.; Lee, J. Y.; Park, V.; Kim, Y.-C. ChemBioChem 2005, 6, 1745. (18) For the silyl protection of propargyl alcohol, see: Snider, B. B.; Shi, Z. J. Am. Chem. Soc. 1994, 116, 549. (19) Schmidt, A. M.; Eilbracht, P. Org. Biomol. Chem. 2005, 3, 2333. (20) Tietze, L. F.; Haunert, F.; Feuerstein, T.; Herzig, T. Eur. J. Org. Chem. 2003, 562. (21) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217. (22) Representative Procedure: Synthesis of 1-Benzyl-3-(tertbutyldimethylsilyloxy)-2-methyl-1H-indole (4b) In an ACE pressure tube under an argon atmosphere the ligand 2,6-di-tert-butyl-4-methylphenol (22.0 mg, 0.1 mmol) is dissolved in 3 mL dry toluene. To this solution N-benzyl-N-phenylhydrazine (257.7 mg, 1.3 mmol), tertbutyldimethylsiloxy-2-propyne (209.0 mL, 1.0 mmol) and Ti(NEt 2) 4 (18 mL, 0.05 mmol) were added. The reaction mixture was heated at 100 °C for 24 h. Then the pressure tube was opened under argon to add ZnCl 2 (410.0 mg, 3.0 mmol). The reaction mixture was heated at 100 °C for further 24 h. After cooling to r.t. the solution was decanted and the dark residue was washed with toluene and EtOAc. After removal of the combined solvents in vacuo and purification by column chromatography (eluent: hexane– EtOAc = 10:1) yielded 1-benzyl-3-(tert-butyldimethylsilyloxy)-2-methyl-1H-indole (175.8 mg, 50%) as light yellow solid (mp 69 °C). 1 H NMR (300 MHz, CDCl 3): d = 7.45–7.40 (m, 1 H), 7.27–7.21 (m, 3 H, m-, p-Ph), 7.10 (m, 1 H), 6.93 (m, 2 H), 6.86–6.87 (m, 2 H, o-Ph), 5.22 (s, 2 H, CH 2Ph), 2.20 (s, 3 H), 0.83 (s, 12 H), 0.15 (s, 6 H) ppm. 13 C NMR (75 MHz, CDCl3): d =136.4 (i-Ph), 135.6, 133.6, 128.9 (m-Ph), 128.4, 127.8 (p-Ph), 125.8 (o-Ph), 121.7, 120.6, 120.8, 120.7, 108.7, 46.9, 25.8, 18.2, 9.1, –5.3 ppm. MS (EI, 70 eV): m/z (relative intensity) = 351 (100) [M + ], 294 (27), 260 (13), 221 (25), 204 (12), 177 (8), 115 (15), 91 (90), 73 (71), 65 (8), 43 (6). HRMS (EI): m/z calcd for C 22H 29NOSi: 351.2013; found: 351.1999. Synlett 2007, No. 7, 1091–1095 © Thieme Stuttgart · New York
3 Publications 84 3.2 Zinc-Promoted Hydrohydrazination of Terminal Alkynes: An Efficient Domino Synthesis of Indoles Karolin Alex, Annegret Tillack, Nicolle Schwarz, Matthias Beller, Angew. Chem. Int. Ed. 2008, 47, 2304-2307; Angew. Chem. 2008, 20, 2337-2340. Contributions: In this paper, I was involved in experimental planning, as well as discussion and argumentation of the results. I contributed significantly to the draft of the manuscript and supported the synthetic work. My contribution as co-author of this paper is approximately 10%.
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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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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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