synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 45 different heteroaryl halides with a range of alkynes in good yields. The ratios between substrate and catalyst were nearby moderate to high in the process. Various heteroaryl halides like indoles, thiophenes, pyridines and quinolines were employed successfully. The examples of Sonogashira reaction of 5-bromoindole with different alkynes are shown in Scheme 36. The bromo-substituted indole was a suitable substrate for Sonogashira coupling. TON’s of 6000-8000 were obtained for the coupling of 5-bromoindole 12 with phenylacetylene 136. Lower TON’s were observed by the coupling with propargyl alcohol 142 and but-3-yn-1-ol 143. The coupling products 144-146 were obtained in excellent yields up to 99%. The results represent economically attractive procedures. Br 12 N H H H H 136 142 143 Ph OH OH [Pd(C 3H 5)Cl] 2/ligand E K 2CO 3 (2 equiv) CuI (0.05 equiv) DMF, 100 °C, 20 h Scheme 36. Sonogashira coupling reaction with 5-bromoindole. HO HO Ph 144 (97%) N H N H 145 (99%) N H 146 (99%) Because of the high price of palladium, their low catalyst loading is a practical advantage and become increasingly important for industrial processes. Sonogashira coupling reactions are not only possible with aryl halides especially indole halides, but also with other substrates like 2-trifluoromethanesulfonyloxyindoles. [118] Rossi and co-workers developed palladium-catalyzed reactions with 2-trifluoromethanesulfonyloxyindole-1-carboxylic acid ethyl ester and different partners. [94] Compound 147 was synthesized first and its reactivity was tested afterwards. The authors prepared 2-aryl, 2-heteroaryl, 2-allyl, and 2-vinyl indoles 148a-f in good to excellent yields by palladium-catalyzed coupling of 147 with commercially available alkynes. Scheme 37 gives an account of the reaction with different alkynes following the Sonogashira protocol.
1 Palladium-catalyzed Coupling Reactions of Indoles 46 OSO2CF3 H R Pd(PPh3) 4 CuI, Et3N DMF, rt, 1h 147 COOEt 148a-f COOEt Ph COOEt nC 5H 11 148a (98%) 148b (92%) 148c (78%) COOEt COOEt OH OH COOEt COOEt COOEt 148d (87%) 148e (92%) 148f (97%) Scheme 37. Palladium-catalyzed reaction with 2-trifluoromethanesulfonyloxyindole-1-carboxylic acid ethyl ester. 2-Alkynyl indole derivatives 148a-f were synthesized in the presence of Pd(PPh3)4/CuI, Et3N in DMF. Starting from commercially available and inexpensive intermediate 1,3-dihydroindol-2-one, they obtained the reactive and stable precursor 147 for 2-carbosubstituted indoles, thus providing a valuable alternative to until that time reported synthetic strategies. In the upper examples the indole part was normally used as the heteroaryl halide unit that was coupled with several alkynes. The group around Abbiati reported about the synthesis of pyrazino[1,2-a]indole achieving by intramolecular cyclization of several 2-carbonyl-1-propargylindoles in the presence of ammonia (Scheme 38). [119] Therefore the authors used the Sonogashira coupling as key step by using the indole as the alkyne source and several aryl halides as coupling partners. The 1-propargyl-1-H-indole-2-carbaldehyd 149a, the 2-acetyl-1-propargyl-1-H-indole 149b, and the 2-benzo-yl-1-propargyl-1-H-indole 149c were synthesized by standard conditions, starting from readily accessible 1-H-indole-2-carbaldehyd, 2-acetyl-1-H-indole and 2-benzoyl-1-H-indole. The following standard palladiumcatalyzed Sonogashira reaction of 149 with different aryl halides (R 2 -X) gave the resultant products 150 in 61-91% yield. Thermal cyclization of the intermediates 150 led to pyrazino[1,2-a]indoles in good yields. HO R
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Leibniz-Institut für Katalyse e. V
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PAPER Coupling Reactions of Electro
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Scheme 2 Ti-catalyzed synthesis of
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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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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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