synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 43 Table 7. Sonogashira cross-coupling reactions with 3-alkynyl-5-bromoindoles. Br R 2 PdCl2(PPh3) 2 (10 mol%) CuI (20 mol%) PPh3 (10 mol%) H R N Et3N/DMF, 70 °C, 48 h R 3 R3 133j-l 134a-d Entry 133 R R 2 R 3 N R R 2 134 Yield [%] 1 j Boc CH2NHTos CH2NHTos a 55 2 k SO2Ph CH2NMe2 CH2NHTos b 83 3 k SO2Ph CH2NMe2 CH2OH c 74 4 l Tos CH2NHTos CH2NMe2 d 77 Indoles are known to exhibit a broad range of biological activity. There is always a great demand for their evaluation as potential drug candidates. Larock et al. reported about a solid-phase synthesis of trisubstituted indoles and their further elaboration through palladium-mediated coupling reactions. [114] The authors developed an iodocyclization process that presented iodo-containing products supported by solid phase. Such an iodo-containing compound is shown in Scheme 34. The immobilized 3-iodoindole 135 was converted with phenylacetylen 136 under standard Sonogashira reaction conditions to the corresponding coupled product 137. The authors were obtained the final solid phase-free compound by tranesterification and isolation of the methyl ester in a yield of 91% with a purity of 93%. O I H Ph O 135 Ph N Me 136 PdCl2(PPh3) 2 CuI, HNEt2 polystyrene Scheme 34. Solid phase Sonogashira coupling with trisubtituted indole. O O 137 Ph N Me Ph
1 Palladium-catalyzed Coupling Reactions of Indoles 44 The group around Nakamura described heterocycles containing propargylic diisopropylamines. [115] These propargyl-diisopropylamines were easily prepared from heterocyclic bromides by Sonogashira coupling reaction. Followed by allene transformation reaction the corresponding heterocyclic allenes were produced in good to high yields. Allenes are very important building blocks for organic synthesis. [116] The heterocyclic allenes precursors were synthesized using Sonogashira coupling reaction of N,N-diisopropylprop-2-ynylamine 139 with different heterocyclic bromides. Scheme 35 shows the coupling reaction of the indole example 138. The reaction was carried out in the presence of Pd(PPh3)4, CuI and Et3N in CH3CN at 60 °C. Br N(iPr) 2 Pd(PPh 3) 4 (5 mol%) CuI (10 mol%) (iPr) 2N N Et3N, CH3CN N 138 Boc 139 140(26%) Boc H 141 (88%) N Boc Scheme 35. Sonogashira coupling reaction of Boc-protected 5-bromoindole with N,Ndiisopropylprop-2-ynylamine. The authors reported that the reaction with N-unprotected 5-bromoindole did not undergo the Sonogashira coupling however, the reaction with N-Boc-5bromoindole 138 gave desired product 140 in a yield of 26%. For the palladiumcatalyzed allene transformation, compound 140 was converted in the presence of Pd2(dba)3·CHCl3 (2.5 mol%) as catalyst, and 1,2-bis[bis(pentafluorophenyl)phosphino]ethan (10 mol%) at 100 °C in CHCl3. The indole allene 141 resulted in a yield of 88%. Santelli and colleagues described the Sonogahira reaction of heteroaryl halides with alkynes catalyzed by a palladium-tetraphosphine-complex. [117] They used the same catalytic system described already in the Suzuki part in Scheme 17. The Tedicyp/PdCl(C3H5)]2 catalytic system catalyzed the Sonogashira reaction of
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Leibniz-Institut für Katalyse e. V
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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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Publikationen 1 Titanium-Catalyzed
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