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C-Acilación enantioselectiva Ni-Catalizada de los lactamos α-sustituidos

Masaki Hayashi¹, Shoshana Bachman¹, Satoshi Hashimoto¹

¹The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.

Journal of the American Chemical Society

|July 5, 2016

Resumen

Los investigadores desarrollaron un nuevo método catalizado por níquel para la acilación C enantioselectiva. Esta estrategia sintetiza eficientemente los lactamos sustituidos por α-cuaternario, específicamente los lactamos β-ceto, con un alto exceso enantiomérico.

Área de la Ciencia:

Química orgánica
Catálisis
Síntesis asimétrica

Sus antecedentes:

Los lactamos son compuestos heterocíclicos importantes con diversas aplicaciones.
La síntesis de estereocentros α-cuaternarios en lactamas sigue siendo un desafío sintético.
Los métodos enantioselectivos son cruciales para producir moléculas quirales con actividades biológicas específicas.

Objetivo del estudio:

Desarrollar una nueva estrategia de enantioselección catalítica de C-acilación.
Para sintetizar de manera eficiente los lactamos sustituidos por α-cuaternario, específicamente los lactamos β-ceto.
Establecer un método para la construcción de estereocentros cuaternarios con alta enantioselectividad.

Principales métodos:

Reacción de acoplamiento de tres componentes catalizada por níquel.
Utilizó enolados de lactamo, benzonitriles y haluros de arilo como materiales de partida.
Se utiliza un ligando de tipo Mandyphos y un aditivo de bromuro de litio (LiBr).

Principales resultados:

Lactamas β-imino sintetizadas con éxito a través del acoplamiento de tres componentes.
La hidrólisis ácida de las β-imino lactamas produjo las β-ceto lactamas objetivo.
Se obtiene un alto exceso enantiomérico (hasta el 94% ee) en la formación de estereocentros cuaternarios.

Conclusiones:

Se ha establecido una estrategia nueva y eficiente para la acilación C enantioselectiva catalítica.
El método desarrollado proporciona acceso a valiosos β-quetolactamas sustituidos por α-cuaternario.
La metodología ofrece una ruta práctica para la construcción de estructuras quirales complejas.

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