synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 59 Br N CH 3 CH 2 Ph NH Ph Pd 2(dba) 3 (2 mol%) ligand H (0.5 mol%) tBuONa (3 equiv) toluene, N 2, 100 °C, 24 h O O 183 184 185(99%) iPr iPr ligand H Scheme 47. Palladium-catalyzed amination of a 5-bromoindole derivative with benzophenone imine. Under optimized reaction conditions in the presence of 2 mol% Pd2(dba)3 and 1,8bisdiisopropylphosphinotriptycene H as catalytic system, tert-BuONa as base, the according product 185 was isolated in a yield of 99%. Fascinating compounds like 183 were effectively aminated by benzophenone imine 184 and led to interesting new structures that represent important building blocks for construction of sensors (anthracene-1,8-diamine) [134] and molecular switches (indole derivatives) [135] . A further application of Buchwald-Hartwig coupling reaction was described by Ganton and Kerr in total synthesis of the (±)-CC-1065 CPI subunit. [136] CC-1065 and the related compounds like duocarmycins are members of a structurally unique family of naturally occurring molecules and remain some of the most rigorously studied antitumor compounds to date. Their derivatives remain as some of the strongest candidates for new exceptionally potent and highly selective therapeutic agents against tumorigenic cells. Structurally CC-1065 consists of two identical central and eastern pyrrolo[3,2-e] indole-4-one subunits linked together to the western subunit by amide bonds through pyrrolidine nitrogen. The key steps of the synthesis were a Diels-Alder reaction and a palladium-catalyzed intramolecular aryl triflate amidation. Scheme 48 pictured two selected examples of the intramolecular amidation. Ph Ph N N CH 3 CH 3
1 Palladium-catalyzed Coupling Reactions of Indoles 60 BzHN TfO OMOM OBn 186 Me N Tos Pd 2(dba) 3 Xantphos Cs 2CO 3 dioxane BzN OMOM OBn 187 (88%) Me N O N H TfO OMOM Me Pd2(dba) 3 Xantphos Cs2CO3 Me N O OMOM N Me 188 OBn N Tos dioxane 189 (61%) OBn N Tos Scheme 48. Intramolecular aryl amidation with complex cross-coupling partners. The amidation reactions of 186 and 188 were done in a Schlenk tube in attendance of Pd2(dba)3 (7 mol%), Xantphos (23 mol%) and Cs2CO3 (1.5 equiv) in dioxane for 22 h. The complex coupling products 187 and 189 were isolated in 88% and 61%, respectively. The intramolecular aryl amidation formed the key intermediate precursor for the CC-1065 subunit. Numerous known indoles, especially amino-functionalized derivatives represent key structures for various biologically active compounds. The amination of 3silyloxy-5-bromoindole 190 with several primary and secondary amines led to new potentially bioactive amino-functionalized indole derivatives. [137] A novel palladium catalyst for Buchwald-Hartwig amination was developed by Beller and co-workers and opened new ways to interesting tryptamine derivatives. In Scheme 49 the general reaction sequence and the resulted coupling products 191a-j can be seen in good to excellent yields. They studied different effects of base, and ligands on the reaction and optimized the reaction conditions to 1 mol% Pd(OAc)2, 2 mol% N-phenyl-2-(di-1-adamantylphosphino)pyrrole I as catalytic system, LiHMDS as base in toluene for 24 h at 100 °C. The corresponding indole products 191a-j obtained in 40-91% yield. This catalytic system works well with different primary and secondary amines and gave a novel class of electron-rich indoles. Me N Tos
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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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Table of Contents Preface .........
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List of Abbreviations Ac Acetyl aq
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Preface The search for drugs is an
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1 Palladium-catalyzed Coupling Reac
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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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