synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 13 Table 3. Suzuki-Miyaura reaction of indole boronic acids, continued. Entry Ar-Cl 47 Ligand Product 48 Yield[%] 2 b N Cl 3 c Cl 4 d Cl N S 5 e S Cl 6 f 7 g Cl Cl N O O H N H NH 2 Me A MeN A B MeN N H B HN B HN NH B HN Another catalyst system for palladium cross-coupling was published by Yu and colleagues. [39] The authors developed a microwave promoted Suzuki coupling reaction of aryl chlorides and boronic acids in an aqueous media in the presence of POPd2 [40] shown in Scheme 10. Microwave irradiation has been reported to promote metal-mediated reactions like Suzuki-Miyaura cross-coupling. [41] They chose an aqueous solvent system (DMF/H2O, 5:1) based on Leadbeater’s work. [42] The use of TBAI as an additive was beneficial in this mixed solvent system, similar to previous reports employing neat water as the solvent. [43] After optimization of the initial reaction conditions by varying temperature, ratio of reactants, and percentage of catalysts the method was applied to the synthesis of 5-arylindoles 50a-g (Scheme 10). Different aryl chlorides 49a-g were converted with indol-5-yl boronic acid 13 via palladium-catalyzed cross-coupling under special conditions, mentioned before, and resulted the desired compounds in good yields (61-76%). S N S N N O H O Me NH 2 77 96 91 90 71 77
1 Palladium-catalyzed Coupling Reactions of Indoles 14 Cl (HO) 2B POPd 2 (3 mol%) TBAI (12 mol%) Cs 2CO 3 (4 equiv) R 49a-g 13 N H microwave, 150 °C DMF/H2O (5/1) 15 min 50a-g 50 a b c d e f g R: H 4-OMe 4-F 4-Me 2-Me 4-CF3 4-CN Yield [%] 61 72 76 71 68 64 75 Scheme 10. Palladium-catalyzed Suzuki-Miyaura reaction of indol-5-yl boronic acid. The next example investigated the synthesis of indoles via palladium-catalyzed Suzuki-Miyaura reaction on a polystyrene solid phase. Combining solid phase synthesis with high throughput screening has made a significant contribution for lead discoveries and optimization in pharmaceutical research. For producing combinatorial libraries, solid phase synthesis is regarded as a very efficient method. [44] Suzuki reactions have been already applied to solid phase synthesis but a limited number of examples were reported for the coupling reaction of immobilized arylmetals with free aryl halides in solution. [45] T. Kasahara and Y. Kondo found a method where immobilized 3-pinacol-substituted indole reacted with different aryl halides under Suzuki standard conditions. [46] The paper describes the preparation of immobilized indolylboron and the subsequent arylation using palladium-catalyst (Scheme 11). The immobilized 3-iodoindole 51 was easily prepared from indole via iodonation followed by immobilization using chlorosulfonylated polystyrene. Continued along palladium-catalyzed borylation [47] via Murata’s protocol [48] the indolylboron 52 was investigated. Palladium-catalyzed cross-coupling was [49] examined subsequently with Pd[P(tert-Bu)3]2 as catalyst and led to the according coupled products 53a-e in good to very good yields. R N H
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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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A novel palladium catalyst for the
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Table 2. Reaction of different amin
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PAPER Coupling Reactions of Electro
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Scheme 2 Ti-catalyzed synthesis of
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mixture was used for the synthesis
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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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Synthesis of Indole-2,3-dicarboxyla
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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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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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Publikationen 1 Titanium-Catalyzed
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