synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 7 After deprotection the desired compound 19 is obtained with a varying amount of the tert-butyl-substituted derivative 20. This type of side product is well known in peptide synthesis using Boc-strategies. Furthermore, the same group reported Suzuki-type coupling reactions with azidesubstituted arenes. [17] Among the different coupling reactions also 1-azido-2bromobenzene [19] 21 reacted with 1H-indole-5-boronic acid 13 to the desired azido-diaryl compound 22 in 88% yield (Scheme 5). Decomposition of 22 by heating gave the annulated aromatic polycycles 23 and 24. N 3 Br (H 2O) 2B 21 13 N H N H 24 (0-5%) Pd(PPh 3) 4 (3-6 mol%) 10% NaHCO 3 aq or Na 2CO 3 (2.4 equiv) DME, 100 °C N H NH N 3 23 (65%) 22 (88%) Scheme 5. Suzuki-Miyaura coupling reaction of 1-azido-2-bromobenzene with 1H-indole-5-boronic acid. Different strategies for the synthesis of annulated indoles such as cryptaustoline and cryttowolin [20] were performed by de Koning and co-workers. [21] These alkaloides have been reported to possess anti-leukemic and anti-tumor activities. Thus, indole-2-yl boronic acid 25, typically prepared with butyl lithium and borate, was dissolved in ethanol and reacted with naphthalene 26 in the presence of Pd(PPh3)4 (10 mol%) and Na2CO3 as base (Scheme 6). [22] The coupling intermediate 27 is obtained in a yield of 96% over two steps. Noteworthy, deprotection of the Boc-group and formation of the aromatic ring [23] gave instead of the expected naphtho[a]carbazole 29 the isoquinoline 28. In addition, other syntheses towards the cryptaustoline nucleus involving Suzuki-Miyaura couplings of indoles as key step have been mentioned. [21] N H N H
1 Palladium-catalyzed Coupling Reactions of Indoles 8 B(OH) 2 Br Boc CHO Pd(PPh3) 4 (10 mol%) Na N 2CO3 aq N DME 25 Boc 26 27 CHO (96% two steps) Scheme 6. Suzuki-Miyaura coupling reaction of indole-2-yl boronic acid and dihydro-naphthalene. When using indoles in Suzuki-Miyaura reactions this chemistry involves in general the utilization of indolyl halides. In this respect, Larock and co-workers analyzed novel 1,4-palladium migrations. [24] More specifically, they observed 1,4-palladiummigration in organopalladium intermediates derived from o-halobiaryls. As an example they examined the reaction of 2-iodo-1-methyl-3-phenylindole 30 and boronic acid 31 (Scheme 7). To avoid that the base activates the aryl boronic acid prior to palladium migration, the system was buffered using a combination of cesium pivalate and pivalic acid. Hence, components 30 and 31 were stirred at 100 °C in the presence of 5 mol% Pd(OAc)2, 5 mol% (PPh2)2CH2 (dppm), 2 equiv of cesium pivalate and 2 equiv of pivalic acid in DMF containing 20 equiv of water. After 3 h product 32 is obtained selectively in 67% yield. Interestingly when 3-(2iodophenyl)-1-methylindole 34 is allowed to react with 31 under the same conditions, product 32 is produced in a yield of 57% along some traces of isomer 33. I N Me Ar-B(OH) 2 Ar = p-MeO 2CC 6H 4 Pd(OAc) 2 (5 mol%) dppm (5 mol%) 32 (67%) 33 (0%) Ar N Me 30 31 32 33 31 34 N Me N 29 Ph Ar Pd(OAc) 2 (5 mol%) dppm (5 mol%) Ar-B(OH) 2 32 (57%) 33 (traces) Scheme 7. 1,4-Palladium-migration of an o-halobiaryl with an arylboronic acid. Ph N 28 N Me I
Page 1 and 2: Leibniz-Institut für Katalyse e. V
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Page 9 and 10: List of Abbreviations Ac Acetyl aq
Page 11 and 12: Preface The search for drugs is an
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1092 N. Schwarz et al. LETTER Table
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1094 N. Schwarz et al. LETTER 2,6-d
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3 Publications 84 3.2 Zinc-Promoted
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Table 2: Reaction of N-methyl-N-phe
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Am. Chem. Soc. 2002, 124, 15168 - 1
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A novel palladium catalyst for the
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Table 2. Reaction of different amin
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3 Publications 94 Experimental Data
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3 Publications 96 (q); 115.3 (d, J
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3 Publications 98 3.4 Palladium-Cat
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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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synthesis and catalytic functionalization of biologically active indoles

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