synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 47 R 1 R 2 -X N O Pd(PPh3) 4,CuI, K2CO3 N DMF, N2, 60 °C 149 150 149a R 1 = H 149b R 1 = Me 149c R 1 = Ph R 2 = Ph, pCl-Ph, mCF 3-Ph, pMeO-Ph, Scheme 38. Sonogashira reaction of 1-alkynyl-indole derivatives. R 1 O N N The Sonogashira reaction as key step was applied in the enantioselective total synthesis of aspidophytine 154 as well (Scheme 39). [120] Aspidophytine is the righthalf of haplophytine 155, a dimeric indole alkaloid isolated from the dried leaves of the plant Haplophyton cimicidum. That is the reason why it is a precursor for biosynthesis and also a possible synthetic intermediate to 155. MeO OMe N H O HO OAc I N O OTBDPS Me N MeO CH(OMe) 2 CO 2Et Halophytine N N OMe Me H O O MeO OMe N H OAc EtO 2C 151 152 153(78%) 155 Pd(PPh 3) 4 (2 mol%) CuI (4 mol%), Et 3N 70 °C, 2 h Scheme 39. Coupling key-step in the synthesis of aspidophytine. N R 2 N OMe Me MeO H 154 Aspidophytine O O OTBDPS CH(OMe) 2 The authors prepared the indole unit 151 commenced with a known benzaldehyde and the desired acetylene unit. The two synthesized fragments were joined to form the 11-membered secondary amine. Sonogashira coupling of 151 and 152 gave
1 Palladium-catalyzed Coupling Reactions of Indoles 48 the 2-alkynylindole derivative 153 in a yield of 78%. Under Sonogashira standard conditions with Pd(PPh3)4, CuI and Et3N they got the key intermediate 153 for the construction of the aspidosperma skeleton. A further application in synthesis of natural structures is the study towards the marine alkaloid chartelline C 161 by Magnus et al.. [121] The authors developed a regioselective Sonogashira coupling of 2,6-dibromoindole at the 2-position with simple acetylenic partners (Scheme 40). The authors were interested to see if a 2,6-dibromoindole 156 exhibited any selectivity in Songashira coupling reaction. Scheme 40 shows the conversion of the dibrominated indole 156 with different alkynes with complete regioselectivity to the 2-coupled indoles 157a-c in good yields under standard Sonogashira coupling reaction conditions. Therefore the choice of the protecting group on the indole nitrogen atom was essential for achieving regioselectivity in Sonogashira coupling reaction. Br CN CN PdCl2(PPh3) 2 CuI, NEt3, 45 °C Br R N N R Br Boc Boc 156 157a-c 157a R = TIPS (92%) 157b R = iPr (67%) 157c R = -C6H4OMe-p (45%) Scheme 40. Sonogashira coupling of 2,6-dibromoindole derivative. The authors applied their findings in the synthesis of chartelline C analogue 160 subsequently. Scheme 41 outlined the development to the desired compound 160 in the presence of the dibrominated indole 156 and the complex alkyne 158. The desired compound 159 was obtained in a yield of 67%. The regioselective Sonogashira coupling reaction was used to synthesize the 2-isoprene-imidazole chain whereas the imidazol was constructed after coupling reaction.
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Leibniz-Institut für Katalyse e. V
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Für meine Eltern Siegfried und Ker
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Mein besonderer Dank gilt Dr. Anneg
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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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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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