synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 55 Under this reaction condition the indole coupling products 173 and 174 were isolated in 99% yield in the presence of Pd(OAc)2 as catalyst, K3PO4 as base in toluene/tert-BuOH as solvent. Additionally to that, they investigated the palladium-catalyzed amination of 5aminoindole 175. Scheme 45 shows the nearly selective palladium-catalyzed amination of 5-aminoindole 175 with two different amines 176 and 178 to product 177 and 179 in very good yields. It is surprising, that a simple arylbromide and arylchloride gave arylation of the 5-amino group at the indole in moderate to high selectivity in attendance of Pd2(dba)3, ligand F (Scheme 43) and K2CO3. H 2N H 2N Pd2(dba) 3 (1 mol%) ligand F (5 mol%) nBu Cl nBu K2CO3 (2.5 equiv) 175 N H 176 tBuOH, 110 °C, 3 h 177 (80%) N H N H Br Me Me Pd 2(dba) 3 (1 mol%) ligand F (5 mol%) PhB(OH) 2 (5 mol%) K 2CO 3 (2.5 equiv) tBuOH, 110 °C, 3 h 175 178 179(74%) Scheme 45. Complementary C-N couplings using Pd-catalyst. Me H 2N Me 180 Me Using copper as catalyst the selectivity switched exclusively to the coupling product 180 (98%). However, it was possible to influence the selectivity by different metal-catalysts to complementary products. In a similar way Queiroz et al. reported about the palladium-catalyzed amination of ethyl-3-bromobenzo[b]thiophene-2-carboxylate 181 with 5-aminoindole 175 (Scheme 46). [128] The precursor 181 was prepared from the corresponding 3amino compound. The 5-aminoindole was used as coupling component and gave N N H Me
1 Palladium-catalyzed Coupling Reactions of Indoles 56 the coupling product 182 after 5 h heating in a yield of 40%, while on leaving the reaction overnight the yield was increased to 63%. Pd(OAc) 2 (3 mol%) Br BINAP (4 mol%) HN H2N Cs2CO3 (1.4 equiv) CO2Et CO2Et S N toluene, 100 °C, 21 h S H 181 175 182 (63%) Scheme 46. Palladium-catalyzed amination of ethyl-3-bromo-benzo[b]thiophene-2-carboxylate with 5-aminoindole. In attendance of 3 mol% Pd(OAc)2 as palladium source, 4 mol% BINAP and 1.4 equiv Cs2CO3 as base in toluene at 100 °C resulted the diarylamine benzo[b]thiophene 182 in good yield. Benzo[b]thiophenes are important heterocycles, either in biologically active molecules or as luminescent components used in organic materials. [129] Pujol and co-workers were also interested in obtaining new compounds with biological activity. Therefore they required an easy source of N-aryl derivatives to serve as precursors. Aryl bromides were coupled with N-compounds to give the corresponding arylamines in the presence of palladium catalyst, suitable ligand, and weak base. [130] They prepared arylamines from interesting substrates by using Pd[P(o-tolyl)3]2Cl2 (0.12 mol%) as catalyst, BINAP (0.0075 mol%) or PPh3 as chelating ligands, and Cs2CO3 as base (1 mmol) without solvent or a few drops of toluene when the starting material was a solid compound. Table 9 shows the coupled products from the synthesis of indoles with different substrates. When 5bromoindole (Table 9, entries 6-9) was treated with 3-fluoroaniline, the arylation took place exclusively at the 1-position over the N-atom. The corresponding N-arylindole was obtained as a single isomeric product at a temperature near 150 °C (Table 9, entries 7 and 8). and the expected 5-(3fluorophenylamimo)indole was not detected under these conditions. NH
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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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PAPER Coupling Reactions of Electro
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3 Publications 108 3.5 Synthesis of
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Scheme 2 Ti-catalyzed synthesis of
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mixture was used for the synthesis
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7.11 (ddd, 1H, J = 8.0 Hz, J = 7.0
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FULL PAPER DOI: 10.1002/ejoc.200800
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Synthesis of Potential 5-HT 6 Recep
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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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