synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 25 Indeed, industrially interesting as well is the synthesis of new melatonin analogues via Suzuki homocoupling. Melatonin plays a major role in the regulation of seasonal cycles and the control of circadian rhythms [82] and has been the focus of clinical interests. The selective melatonin synthesis is still a challenge. Viaud-Massuard and co-workers concentrated thereby on developing a catalytic approach to dimers of indoles. [83] The homocoupling of (5-bromo-1H-indol-3yl)acetonitrile 78 using borane 79 generated in situ, gave the corresponding dimer 80 in 53% yield. Compound 80 was finally converted to the final, compound 81 after hydrogenation over Raney nickel and concomitant N-acetylation (Scheme 18). Br N H CN O B O N H CN PdCl 2(dppf) 2M Na 2CO 3 78 79 80 AcHN Scheme 18. Palladium-catalyzed homocoupling of (5-bromo-1H-indol-3-yl)acetonitrile. H N NC H N 81 N H NH Ac N H (53% for 2 steps) In a similar way described below, (5-bromoindo-1-yl)acetonitrile 82 was coupled with the according borane to the dimer 83 within a 2-step yield of 37% in the presence of PdCl2(dppf) (Scheme 19). The use of organoboron compounds is valued because the inorganic by-products of the reactions are nontoxic and can be readily removed by simple workup procedures. Many parameters as shown above in several examples can be change to success in the Suzuki-Miyaura reaction. The metal/ligand systems that facilitate the cross-coupling with different electrophiles have been the most extensively studied. CN
1 Palladium-catalyzed Coupling Reactions of Indoles 26 Br 82 N CN 1)Bis(pinacolatodiborane), PdCl 2(dppf), KOAc, DMF, 2 h 2) 82, PdCl 2(dppf), 2M Na 2CO 3aq N CN N 83 (37 % within 2 steps) CN Scheme 19. Palladium-catalyzed homocoupling of (5-bromoindo-1-yl)acetonitrile. Different palladium sources in the absence of ligands [84] to very elaborate catalyst/ligand systems [85] have been applied. The development of several airstable catalysts has been reported to improve the catalyst turnover, to achieve the coupling of less reactive electrophiles or to permit coupling with hindered substrates. [86] The use of alternative organoborone coupling partners is an underdeveloped area. The boronic acids are subject to cyclic trimerization and the resulting uncertainties in stoichiometry require an excess of these compounds in coupling reactions. The use of boronic esters can solve that problem. Then again, there is a lack of atom economy and additional purification steps, especially when catechol and pinacol are used as the alcohol moiety. One alternative to boron reagents are potassium trifluoroborate derivatives. These are monomeric solids, easily prepared from organoboronic acids or esters by treatment with an aqueous solution of KHF2. [87] They are in general air stable and environmentally friendly. No protecting groups are necessary bearing ketones, alcohols, aldehyds, or carboxylic acids. Finally the trifluoroborate system appeared less subject to protodeboronation than other boron derivatives. Molander and Biolatto investigated palladium-catalyzed Suzuki-Miyaura coupling reactions of potassium aryl- and heteroaryltrifluoroborates. [88] The authors described that generally the trifluoroborate coupling system proved to be more reactive than the corresponding boronic acids or esters under Suzuki standard reaction conditions. They demonstrated many successful ligandless couplings of reagents bearing a variety of functional groups. All reactions were carried out in air with no lost in yield. In general a lower catalyst loading, lower temperatures and shorter reaction times were utilized. Another advantage was the ability to use electron-deficient arylborons routinely. Following Scheme 20 shows the cross-
Page 1 and 2: Leibniz-Institut für Katalyse e. V
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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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