synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 53 The reaction was accompanied by formation of the dehydro-brominated byproduct with a yield of 30%. The last example shows the palladium-catalyzed amidation of indole 163 with urea. Unlike amination, the amidation of 6bromoindole 163 was characterized by high yield of product 166. The yield of the corresponding N,N-diethylhetarylurea in the presence of 3,5-(CF3)2Xantphos was optimized to 91%. While in cases above amination with bromoindoles bearing a free NH did not succeed, the next examples will demonstrate the first coupling of amines with chloro- and bromoindoles bearing a free NH-group. Buchwald and co-workers reported about the palladium-catalyzed amination of different heteroaryl halides by utilizing bulky electron-rich biaryl phosphine ligands. [126] a) b) X Products: N Pd2(dba) 3 (2 mol%) ligand F (8 mol%) tBuONa (1.4 equiv) N Cl N S N H toluene, 70 °C, 15-20 h S 167 1 168 (73%) N H 12 X = 5-Br 169 X = 6-Cl H N N H HN(R 1 )R 2 O N iPr PCy 2 iPr iPr ligand F Pd2(dba) 3 (1 mol%) ligand F, G (4 mol%) LiHMDS (1.2 equiv) R THF, 65 °C, 24 h N H 2 (R1 )N N H Me 2N Bu 2N ligand G PCy 2 N H 170a-d 170a (96%) 170b (90%) 170c (51%) 170d (66%) Scheme 43. a) Palladium-catalyzed amination of benzothiazole with indole. b) Palladium-catalyzed amination of halo-indoles. N N H
1 Palladium-catalyzed Coupling Reactions of Indoles 54 Scheme 43 imaged on one hand the palladium-catalyzed amination of 2chlorobenzothiazole 167 and indole 1 as the coupling partner (a) and on the other hand the amination of 5-bromoindole 12 and 6-chloroindole 169 as the halide component with different amines to the desired coupling products 168 and 170a-d (b). Bulky electron-rich biaryl ligands F and G were employed for these reactions. The product 168 from the coupling of 2-chlorobenzothiazole 167, in the presence of Pd2(dba)3/ligand F (1:4) as catalyst system, tert-BuONa as base in toluene at 100 °C, was isolated in a yield of 73%. Finally, 5-bromoindole 12 and 6-chloroindole 169, possessing a free NH, were viable coupling partners with anilines and acyclic and cyclic secondary alkylamines. Using the procedure in Scheme 43 (b) with Pd2(dba)3/ligand F or G as catalyst system and 2.2 equiv LiHMDS as base in THF at 65 °C for 24 h gave the according products 170a-d in excellent to good yields, respectively. The more difficult reaction with n-BuNH2 afforded 51% of the desired product 170c. An acceptable yield for the coupling of 6-chloroindole 169 with piperidine to structure 170d was only obtained with ligand F in a yield of 66%. Ligand F was also used in the palladium-catalyzed amination of aryl benzenesulfonates, reported by the same group. [127] The use of benzenesulfonates typically provided higher yields and shorter reaction times as tosylates. As can be seen in Scheme 44, the reaction of a benzenesulfonate 171 and an aryl tosylate 172 with indole 1 led to the wanted products 173 and 174 in excellent yields. In both cases it was necessary to add a catalytic quantity of phenyl boronic acid to ensure complete conversion of the Pd(II) precatalyst to Pd(0). tBu 171 172 OSO 2Ph OTos 1 N H Pd(OAc) 2 (2 mol%) ligand F (5 mol%) PhB(OH) 2 (5 mol%) K 3PO 4 toluene, tBuOH (5:1) 90-110 °C N 173 (>99%) 174(>99%) Scheme 44. Palladium-catalyzed amination of aryl benzene-sulfonate and aryl tosylate with indole. N tBu
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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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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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