Efficient total synthesis of neocryptolepine and synthetic access to 6-methylquinindoline from a common intermediate

A convenient approach toward the indoloquinolines neocryptolepine and 6-methylquinindoline from a common intermediate, is reported. Both sequences, designed for maximum use of accessible reagents and robust conditions, are straightforward and efficient. They involved the amidation of 2- aminobenz...

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Autores principales: Kaufman, Teodoro Saúl, Larghi, Enrique Leandro, Bracca, Andrea Beatriz Juana, Heredia, Daniel Alejandro, Mendez, María Virginia
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: The Royal Society of Chemistry 2017
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Acceso en línea:http://hdl.handle.net/2133/9279
http://hdl.handle.net/2133/9279
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Sumario:A convenient approach toward the indoloquinolines neocryptolepine and 6-methylquinindoline from a common intermediate, is reported. Both sequences, designed for maximum use of accessible reagents and robust conditions, are straightforward and efficient. They involved the amidation of 2- aminobenzaldehyde (prepared by iron-mediated reduction of 2-nitrobenzaldehyde) with 2- nitrophenylacetic acid, followed by a K2CO3-assisted cyclization to form a 3-(2-nitrophenyl)quinolin-2- one as the common precursor. Me2CO3-mediated N-methylation of the lactam, reduction of the nitro moiety and final cyclization resulted in 55% overall yield of neocryptolepine, whereas cyclocondensation and N-methylation afforded 79% overall yield of 6-methyl quinindoline. Thus, the sequences toward the targets entailed two POCl3-promoted C–N bond forming reactions, two Fe-mediated nitro group reductions and two base-promoted transformations.