Los 3,4-diazafosfolanos quirales resueltos y su aplicación a la alquilación alilica asimétrica y catalítica
Thomas P Clark1, Clark R Landis
1Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|September 25, 2003
Resumen
Los investigadores desarrollaron nuevas fosfinas quirales para aplicaciones catalíticas. Estos nuevos compuestos demuestran una alta enantioselectividad en reacciones de alquilación alilica catalizadas por paladio, mostrando una promesa para la síntesis asimétrica.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Catalización asimétrica por catálisis asimétrica.
- Química de los organofosforados Química de los organofosforados
Sus antecedentes:
- Las fosfinas quirales son ligandos cruciales en la catálisis asimétrica, permitiendo la síntesis de compuestos enantioméricamente puros.
- El desarrollo de rutas sintéticas eficientes para nuevos ligandos quirales de fosfina es esencial para el avance de las metodologías catalíticas.
- La alquilación alilica catalizada por paladio es una herramienta poderosa para la formación de enlaces carbono-carbono, que a menudo requiere ligandos quirales para la enantioselectividad.
Objetivo del estudio:
- Para sintetizar una nueva clase de ligandos quirales de fosfina.
- Para investigar la utilidad de estos ligandos en la alquilación alilica asimétrica catalizada por el paladio.
- Para explorar la influencia de la estructura del ligando y las condiciones de reacción en la enantioselectividad.
Principales métodos:
- Reacción de condensación de una sola olla para sintetizar el precursor de la fosfina racémica.
- Resolución de la mezcla racémica a través de la cristalización de sales diastereoméricas.
- Acoplamiento de la fosfina resuelta con aminoácidos y aminas para generar biblioteca de ligandos quirales.
- La alquilación alilica asimétrica catalizada por paladio utilizando las fosfinas quirales sintetizadas.
Principales resultados:
- Se sintetizó una nueva fosfina, el rac-N,N'-ftaloil-2,3-(2-carboxifenil) -fenil-3,4-diazafosfolano (rac-2), con un rendimiento del 88%.
- Se accedió a las fosfinas quirales (3) a través de la resolución y posterior derivación.
- Se lograron altas enantioselectividades (hasta el 97% ee) en la alquilación alilica catalizada por paladio de los acetatos de alilo.
- Se observó una sensibilidad significativa de la enantioselectividad a los sustitutos de aminoácidos y la presencia de sales de PF6.
Conclusiones:
- Se estableció un método novedoso y eficiente para sintetizar diversos ligandos quirales de fosfina.
- Las fosfinas quirales sintetizadas son ligandos efectivos para la alquilación alilica asimétrica catalizada por el paladio.
- El diseño de los ligandos, particularmente los apéndices de aminoácidos y sus contrapartes, juega un papel crítico en el logro de una alta enantioselectividad.
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