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El aditivo catalítico de Lewis permite la alilación selectiva borilativa α-C-H catalizada por el cobre de las aminas

Borja Pérez-Saavedra¹, Álvaro Velasco-Rubio¹, Eva Rivera-Chao¹

¹Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

Journal of the American Chemical Society

|August 24, 2022

Resumen

Este estudio presenta un nuevo método catalizado por el cobre para la síntesis de aminas secundarias cíclicas funcionalizadas a partir de O-benzoil hidroxilaminas. Este enfoque ofrece una mejor tolerancia y selectividad del grupo funcional en la síntesis orgánica.

Área de la Ciencia:

Química orgánica
Química sintética
Catálisis

Sus antecedentes:

Las aminas alicíclicas son sintonas cruciales para los productos farmacéuticos y naturales.
Los métodos actuales de funcionalización a menudo requieren grupos de protección o reactivos agresivos, lo que limita el alcance.
El desarrollo de métodos selectivos y suaves para la funcionalización de aminas sigue siendo un desafío clave.

Objetivo del estudio:

Desarrollar un nuevo método catalizado por cobre para la funcionalización α de aminas secundarias cíclicas.
Para permitir la síntesis de estructuras de aminas complejas con alta regio-, estereo- y quimioselectividad.
Superar las limitaciones de los métodos existentes en cuanto a la tolerancia del grupo funcional y la dureza del reactivo.

Principales métodos:

Acoplamiento catalizado por cobre de las hidroxilaminas O-benzoil con los alenos y el bis (pinacolato) diboro.
Utilizando un aditivo catalítico de Lewis para controlar las vías de reacción.
Generación in situ de iminas alicíclicas y posterior formación de enlaces C-C.

Principales resultados:

Transformación exitosa de las hidroxilaminas O-benzoil en aminas secundarias cíclicas α-funcionalizadas.
Se ha demostrado una alta regioselectividad, estereo- y quimioselectividad en la reacción de acoplamiento.
El aditivo de la base de Lewis suprimió efectivamente la formación de enlaces C-N no deseados, promoviendo la formación de enlaces C-C deseados.

Conclusiones:

Se ha establecido un nuevo y eficiente protocolo catalizado por cobre para las aminas secundarias cíclicas funcionalizadoras.
Este método proporciona una ruta versátil a valiosos bloques de construcción de aminas con un excelente control de la selectividad.
La estrategia desarrollada ofrece un avance significativo en la química orgánica sintética, en particular para el descubrimiento de fármacos y la síntesis de productos naturales.

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