Síntesis enantioselectiva de amidas y aminas cíclicas a través de una metátesis asimétrica de cierre de anillo
Elizabeth S Sattely1, G Alexander Cortez, David C Moebius
1Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
Journal of the American Chemical Society
|June 9, 2005
Resumen
Este estudio presenta métodos catalíticos eficientes para sintetizar amidas y aminas cíclicas bicíclicas N-fusionadas ópticamente enriquecidas. Estos métodos proporcionan acceso a valiosos bloques de construcción quirales para la síntesis de moléculas complejas.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Catalización asimétrica por catálisis asimétrica.
- Metodología sintética de la metodología sintética.
Sus antecedentes:
- Las aminas cíclicas quirales y las estructuras bicíclicas N-fusionadas son motivos cruciales en las moléculas biológicamente activas.
- Las rutas sintéticas eficientes y enantioselectivas para estos compuestos son muy buscadas en la química medicinal y el descubrimiento de fármacos.
Objetivo del estudio:
- Desarrollar nuevos métodos catalíticos asimétricos para la síntesis de amidas y aminas cíclicas bicíclicas N-fusionadas ópticamente enriquecidas.
- Explorar el alcance y las limitaciones de estas estrategias sintéticas.
- Demostrar la utilidad de los productos quirales sintetizados en otras transformaciones químicas.
Principales métodos:
- Desimetrización catalizada por molibdeno de sustratos de polieno achiral para la síntesis de amidas bicíclicas fusionadas con N.
- Síntesis asimétrica catalítica de aminas cíclicas insaturadas de anillo pequeño y mediano.
- Funcionalización regioselectiva y diastereoselectiva de las olefinas en productos de aminas quirales.
Principales resultados:
- Síntesis de amidas 5,6-, 5,7- y 5,8-bicíclicas con hasta un >98% de exceso enantiomérico (ee).
- Síntesis altamente enantioselectiva (hasta 97% ee) de aminas cíclicas insaturadas de anillo pequeño y mediano.
- Funcionalizaciones regioselectivas y diastereoselectivas exitosas de las aminas cíclicas quirales sintetizadas.
- Formación de alquenos cíclicos trisubstituidos y disubstituidos con alta pureza óptica.
Conclusiones:
- Los métodos catalíticos desarrollados proporcionan un acceso eficiente a valiosas amidas cíclicas y aminas cíclicas N-fusionadas enriquecidas ópticamente.
- Estos bloques de construcción quirales no son fácilmente accesibles a través de otras rutas sintéticas.
- Los compuestos sintetizados son adecuados para la síntesis total enantioselectiva de moléculas complejas biológicamente activas.
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