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Arilación catalizada por Rh (I) de heterociclos a través de la activación de enlaces C-H: alcance ampliado a través
Jared C Lewis1, Ashley M Berman, Robert G Bergman
1Department of Chemistry, University of California and Division of Chemical Sciences, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Journal of the American Chemical Society
|February 7, 2008
Resumen
Un nuevo método de arilación directa catalizada por Rh permite un acoplamiento eficiente de azoles y bromuros de arilo. Este proceso tolerante al grupo funcional utiliza un nuevo ligando y simplifica las reacciones y el aislamiento del producto.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- La catálisis es la catálisis.
- Química Medicinal La Química Medicinal es un campo de estudio de la química medicinal.
Sus antecedentes:
- La arilación directa de los heterociclos es crucial para sintetizar compuestos farmacéuticamente relevantes.
- Los métodos existentes que utilizan catalizadores de paladio (Pd) o cobre (Cu) a menudo carecen de tolerancia al grupo funcional y requieren condiciones duras.
- Los azoles, importantes farmacóforos, presentan desafíos únicos para la arilación directa debido a sus propiedades electrónicas.
Objetivo del estudio:
- Desarrollar un método novedoso, práctico y tolerante al grupo funcional para la arilación directa de azoles con bromuros de arilo.
- Identificar un sistema catalizador altamente activo y térmicamente estable para esta transformación.
- Establecer condiciones de reacción que simplifiquen el manejo, la purificación y sean compatibles con la síntesis de microondas.
Principales métodos:
- Arilación directa catalizada por el rodio (Rh) utilizando bromuros de arilo.
- Empleando un ligando de bajo peso molecular fácilmente preparado, Z-1-tert-butil-2,3,6,7-tetrahidrofosfepina, que se coordina con el Rh de una manera P-olefina bidentada.
- Utilizando la sal de tetrafluoroborato del correspondiente fosfonio para el ensamblaje estable al aire y llevando a cabo reacciones en THF o dioxano.
Principales resultados:
- Exitosa arilación directa de varios azoles farmacéuticamente importantes con bromuros de arilo.
- Tolerancia demostrada al grupo funcional, acomodando a los socios de acoplamiento incompatibles con los catalizadores Pd o Cu.
- Se obtienen excelentes rendimientos del producto en 2 horas utilizando el calentamiento por microondas.
- Simplificación de la configuración de la reacción y el aislamiento del producto en comparación con los disolventes tradicionales de amida de alta ebullición.
Conclusiones:
- El método desarrollado catalizado por Rh ofrece una ruta práctica y eficiente para la arilación directa de azoles.
- El nuevo ligando de fosfina y las condiciones de reacción proporcionan un sistema catalítico robusto y versátil.
- Este enfoque facilita la síntesis de derivados azólicos complejos con amplia aplicabilidad en química medicinal.
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