Inversión estereoquímica de un reactivo de grignard estabilizado en ciano: efectos notables de la estructura del
Ming Gao1, Neeraj N Patwardhan, Paul R Carlier
1Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
Journal of the American Chemical Society
|August 28, 2013
Resumen
La identidad y concentración del disolvente tienen un impacto significativo en la estabilidad de configuración de los reactivos quirales de Grignard. Los disolventes etéreos como el THF y el 2-MeTHF aceleran las tasas de epimerización en comparación con el éter dietílico, lo que afecta a los resultados de síntesis asimétrica.
Área de la Ciencia:
- Química organometálica Química orgánica de los metales.
- Síntesis asimétrica de síntesis.
- La estereoquímica es la estereoquímica.
Sus antecedentes:
- Los reactivos organometálicos quirales son cruciales para la síntesis asimétrica.
- La estabilidad de configuración de estos reactivos es esencial para el éxito de las reacciones.
- Comprender los factores que afectan la estabilidad, como los efectos del disolvente, es clave.
Objetivo del estudio:
- Para investigar la epimerización de un reactivo quiral de Grignard.
- Para determinar la influencia de los disolventes etéreos en la estabilidad de la configuración.
- Para cuantificar el efecto de la identidad y concentración del disolvente en las tasas de epimerización.
Principales métodos:
- El intercambio Mg/Br de un bromonitrilo para formar un reactivo quiral de Grignard.
- Medición de las constantes de velocidad de epimerización (k(tc)) a bajas temperaturas (195 K).
- Análisis de las proporciones de diastereómeros del producto de deuteración a lo largo del tiempo.
- Estoiquiometría y estudios dependientes de la concentración en varios disolventes etéreos y tolueno.
Principales resultados:
- El intercambio Mg/Br mostró una alta retención en el éter dietílico (Et2O) pero menor en el 2-MeTHF y el THF.
- Las tasas de epimerización variaron dramáticamente con el disolvente: 26 veces más rápido en Et2O, 800 veces en 2-MeTHF y 1300 veces en THF en comparación con 0.12 M Et2O en tolueno.
- Es probable que el reactivo de Grignard exista como un heterodimero en Et2O, con una epimerización que no requiere desagregación.
- El análisis indicó una rápida solvación incremental que precede a la separación de pares de iones que limita la velocidad.
Conclusiones:
- La identidad y la concentración del disolvente influyen profundamente en la estabilidad de configuración de los reactivos quirales de Grignard.
- El estudio proporciona un costo entrópico estimado para la captura del ligando del disolvente (-13 ± 3 eu).
- Se propuso y respaldó computacionalmente una potencial vía de epimerización de "viaje conducido ionogénico".
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