Control de Felkin sobresaliente: un método general para adiciones controladas por quelación altamente
Gretchen R Stanton1, Corinne N Johnson, Patrick J Walsh
1P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
Journal of the American Chemical Society
|March 12, 2010
Resumen
Este estudio introduce un nuevo método para controlar las adiciones nucleófilas a los sililoxialdehídos, promoviendo productos controlados por quelación con alta diastereoselectividad. Este avance ofrece una herramienta valiosa para sintetizar moléculas complejas, incluidos los productos naturales.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- La síntesis estereoselectiva de síntesis.
Sus antecedentes:
- Las adiciones nucleófilas a los aldehídos alfa-sililoxi suelen seguir vías de no quelación (modelo Felkin-Anh) debido a los efectos estéricos y electrónicos del grupo sililo.
- Lograr productos de adición controlados por quelación con alta diastereoselectividad ha sido un desafío utilizando reactivos organometálicos achirales.
Objetivo del estudio:
- Desarrollar un método general para promover el control de la quelación en las adiciones nucleófilas a los aldehídos alfa-sililoxi.
- Para lograr una alta diastereoselectividad en la formación de productos de adición controlados por quelación.
Principales métodos:
- Los dialquilzincos utilizados, los dialquilzincos funcionalizados y los reactivos de vinilzinco para la adición a los aldehídos alfa-hidroxi protegidos por sililo.
- Se emplean haluros o triflados de alquilzinco (RZnX) para promover la vía controlada por la quelación.
- Mecanismos de reacción investigados utilizando estudios de RMN y diferentes estructuras de sustrato.
Principales resultados:
- Se logra una alta selectividad para los productos controlados por quelación (razones diastereoméricas de 10:1 a >20:1).
- Se ha demostrado una alta tolerancia del grupo funcional característica de los reactivos organozinc.
- Se observó un aumento de las tasas de reacción y la diastereoselectividad en presencia de RZnX, lo que apoya un mecanismo de quelación.
Conclusiones:
- Desarrolló un método versátil para acceder a productos de adición controlados por quelación a los aldehídos alfa-sililoxi con excelente diastereoselectividad.
- Las condiciones suaves del método, la tolerancia del grupo funcional y la alta selectividad lo hacen valioso para la síntesis de productos naturales.
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