synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 35 Another interesting class of compounds is the short chain 4-substituted class of indoles. The structure is found in many attractive targets like the �v�� antagonist that belongs to the heterodimeric integrin superfamily. It is known that the transmembrane vitronectin receptor, �v�� integrin, has recognized as emerging potential therapeutic treatment for various diseases like osteoporosis, arthritis and metastatic cancer. Raboisson and co-workers performed the identification of a novel class of less flexible 1,4-disubstituted indoles with single digit nanomolar binding affinity for �v��and��v��receptors. [105] The key intermediate 114, exhibit in Scheme 27, was obtained by Heck coupling reaction between the commercially available 4-bromoindole 112 and the Boc-protected 7-vinyl-1,2,3,4-tetrahydronaphthyridine 113. In the presence of Pd(OAc)2 and tri-(o-tolyl)phosphine as ligand, Et3N as base in DMF, the coupling product resulted in a yield of 63% after purification by column chromatography. Br N H 112 113 N N Boc Pd(OAc) 2 (8 mol%) P(o-toly) 3 (24 mol%) Et 3N, DMF,100 °C 18 min microwave N N Boc N H 114 (63%) Scheme 27. Heck coupling reaction between 4-bromoindole and the Boc-protected 7-vinyl-1,2,3,4tetrahydronaphthyridine. Larock and colleagues investigated the synthesis of 3-iodoindoles via Pd/Cucatalyzed coupling of N,N-dialkyl-2-iodoanilines and terminal alkynes, followed by electrophilic cyclization. [106] The 3-iodoindoles, produced by this chemistry are useful for the synthesis of a wide variety of substituted indoles. They were further functionalized by applying palladium-catalyzed coupling reactions. They found nbutyl E-3-(1-methyl-2-phenylindole-3-yl)propenoate 117 with an overall yield of 64% (Scheme 28), respectively from N,N-dimethyl-o-iodoaniline and phenyl acetylene by the two-step coupling/cyclization process, followed by the palladiumcatalyzed cross-coupling.
1 Palladium-catalyzed Coupling Reactions of Indoles 36 I N Me Ph CO 2-nBu Pd(OAc) 2 (5 mol%) Na 2CO 3 (1 equiv) nBuNCl DMF, 80 °C N Me 115 116 117 (64%) Scheme 28. Palladium-catalyzed Heck reaction of 3-iodoindole. CO 2-nBu Similarly the group around Lautens gave an account of a tandem palladiumcatalyzed multicomponent reaction of thiophenes and indoles. [107] The authors constructed tri-substituted thiophenes in good yield by palladium-catalyzed tandem alkylation/alkenylation reaction of 3-iodothiophene. Finally they described one indole example based on their method (Scheme 29). They proposed that Pd(0) inserts into the C-I bond of 3-iodoindole 118 followed by carbopalladation of norbornene. Activation of C-H in 2-position formed the according intermediate. Oxidative addition of the alkyl iodide led to the Pd(IV) species and reductive elimination generated the alkylated indole product. Heck reaction with tertbutylacrylate yielded the product 119 in 81%. They assumed that an excess of norbornene is needed to compete with the direct Heck pathway. During their research they observed that the protecting group at the nitrogen is crucial to the efficiency of the reaction. The use of the Me-protected indole resulted only in the direct Heck product. Pd(OAc) 2 (10 mol%) PPh3 (22 mol%) norbornene (6 equiv) CO2tBu I Cs2CO3 (3 equiv) tbutyl acrylate (6 equiv) iodobutane (6 equiv) nBu N DME, 90 °C, 16 h N Tos Tos 118 119 (81 %) Scheme 29. Palladium-catalyzed tandem alkylation/alkenylation reaction of Tos-protected 3iodoindole. About an aryl-aryl palladium-migration via Heck coupling of o-halobiaryls reported Campo et al.. [24] They found that, upon carrying out Heck reactions and Suzuki cross-couplings with o-halobiaryls under various conditions led to mixtures of the Ph
Page 1 and 2: Leibniz-Institut für Katalyse e. V
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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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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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Publikationen 1 Titanium-Catalyzed
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