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A general method for the metal-free, regioselective, remote C–H halogenation of 8-substituted quinolines

An operationally simple and metal-free protocol for geometrically inaccessible C5–H halogenation of a range of 8-substituted quinoline derivatives has been established. The reaction proceeds under air, with inexpensive and atom economical trihaloisocyanuric acid as a halogen source (only 0.36 equiv....

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Detalles Bibliográficos
Autores principales: Motati, Damoder Reddy, Uredi, Dilipkumar, Watkins, E. Blake
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892134/
https://www.ncbi.nlm.nih.gov/pubmed/29675222
http://dx.doi.org/10.1039/c7sc04107a
Descripción
Sumario:An operationally simple and metal-free protocol for geometrically inaccessible C5–H halogenation of a range of 8-substituted quinoline derivatives has been established. The reaction proceeds under air, with inexpensive and atom economical trihaloisocyanuric acid as a halogen source (only 0.36 equiv.), at room temperature. Exceptionally high generality with respect to quinoline is observed, and in most instances, the reaction proceeded with complete regioselectivity. Quinoline with a variety of substituents at the 8-position gave, exclusively, the C5-halogenated product in good to excellent yields. Phosphoramidates, tertiary amides, N-alkyl/N,N-dialkyl, and urea derivatives of quinolin-8-amine as well as alkoxy quinolines were halogenated at the C5-position via remote functionalization for the first time. This methodology provides a highly economical route to halogenated quinolines with excellent functional group tolerance, thus providing a good complement to existing remote functionalization methods of quinolin-8-amide derivatives and broadening the field of remote functionalization. The utility of the method is further showcased through the synthesis of several compounds of biological and pharmaceutical interest.