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Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)
Published on: June 20, 2014
Los enlaces C-H como una funcionalidad ubicua: un enfoque general para los pirazoles arilados complejos a través de
Roman Goikhman1, Teresa L Jacques, Dalibor Sames
1Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.
Journal of the American Chemical Society
|February 12, 2009
Resumen
Este estudio introduce un nuevo método de arilación catalítica C-H para los pirazoles, permitiendo la síntesis regioselectiva de triarilpirazoles complejos. La nueva estrategia "SEM switch" permite un control preciso de la colocación de sustitutos para aplicaciones farmacéuticas.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Metodología sintética de la metodología sintética.
- Química Medicinal La Química Medicinal es un campo de estudio de la química medicinal.
Sus antecedentes:
- Los pirazoles son heterociclos cruciales en productos farmacéuticos y ligandos de proteínas.
- Los métodos sintéticos existentes para los pirazoles a menudo carecen de eficiencia y control regional.
- Existe una demanda continua de rutas sintéticas innovadoras para acceder a diversos derivados del pirazol.
Objetivo del estudio:
- Desarrollar la primera arilación catalítica intermolecular C-H de los pirazoles.
- Establecer un método regioselectivo para la síntesis de pirazoles arilados complejos.
- Crear una estrategia versátil para acceder a pirazoles completamente sustituidos con regioquímica controlada.
Principales métodos:
- Arilación catalítica intermolecular de C-H mediante el uso de un sistema de paladio-pivalato.
- Desarrollo de un "interruptor SEM" para la correlación C-3 regioselectiva.
- Arilación secuencial en las posiciones C-5 y C-3.
- N-alquilación para la introducción de un sustituto de aminas regioselectivo.
- Bromado y acoplamiento Suzuki para la arilación C-4.
Principales resultados:
- Se identificó un sistema catalítico eficaz de pivalato de paladio para la arilación C-H del pirazol.
- Se ha mapeado la reactividad de los enlaces C-H del pirazol (C-5 > C-4 >> C-3).
- El "interruptor SEM" permitió una arilación eficiente en la posición C-3 previamente no reactiva.
- Se logró una síntesis rápida de 3,4,5-triarilpirazoles con un control regional completo.
- Se ha demostrado la N-alquilación regioselectiva de pirazoles protegidos por SEM.
Conclusiones:
- La arilación catalítica C-H desarrollada, combinada con el "interruptor SEM" y la N-alquilación, ofrece una ruta rápida y regioselectiva a los pirazoles completamente sustituidos.
- Esta estrategia proporciona acceso a diversos andamios de pirazol a partir de materiales de partida simples.
- El método es aplicable tanto a los pirazoles protegidos como a los libres, mejorando su utilidad sintética.
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