Se puede acceder a cetonas y aldehídos no racémicos no funcionalizados, alfa-epimerizables, mediante la resolución
Janez Kosmrlj1, Leland O Weigel, David A Evans
1Chemical Process R&D, Lilly Research Laboratories, Indianapolis, IN 46285-4813, USA. janez.kosmrlj@uni-lj.si
Journal of the American Chemical Society
|March 13, 2003
Resumen
Este estudio introduce un método simple de resolución dinámica inducida por cristalización (CIDR) para convertir eficientemente los aldehídos y cetonas racémicos en un solo enantiómero. El proceso logra altos rendimientos y exceso enantiomérico, ofreciendo un enfoque práctico para la síntesis de compuestos quirales.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Síntesis asimétrica de síntesis.
- La cristalización es la cristalización.
Sus antecedentes:
- La desacemización de los compuestos quirales es crucial para sintetizar sustancias enantioméricamente puras.
- Los métodos existentes pueden ser complejos o carecer de eficiencia para un amplio alcance de sustrato.
Objetivo del estudio:
- Desarrollar un protocolo de desacimización operacionalmente simple y altamente eficiente para aldehídos y cetonas.
- Investigar el mecanismo y el alcance del nuevo proceso de resolución dinámica inducida por cristalización (CIDR).
Principales métodos:
- Formación de iminas a partir de aldehídos/cetonas racémicas y una amina quiral auxiliar (trans-(1R,2R)-1-amino-6-nitroindan-2-ol).
- Cristalización diastereoselectiva de los derivados de imina.
- Hidrólisis bifásica para recuperar el auxiliar quiral y obtener el producto enriquecido enantioméricamente.
Principales resultados:
- Se logró una conversión casi completa de las mezclas racémicas en enantiómeros individuales.
- Se observaron altos rendimientos y exceso enantiomérico (ee) para varios sustratos, incluida la 2-metilciclohexanona (97%/92% ee) y el 2-etilhexanal (94%/98% ee).
- El proceso demostró efectividad para una gama de cetonas y aldehídos.
Conclusiones:
- El protocolo CIDR desarrollado es un método poderoso y práctico para la desacemización.
- La alta eficiencia se atribuye a las interacciones específicas en estado sólido (pi-stacking y enlace de hidrógeno) entre el imine y el auxiliar quiral.
- El proceso tiene potencial para aplicaciones industriales en síntesis quiral.
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