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Aminación de arenas radicales regioselectivas para la síntesis concisa de ortofenilendiaminas

James E Gillespie¹, Charlotte Morrill¹, Robert J Phipps¹

¹Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Journal of the American Chemical Society

|June 15, 2021

Resumen

Los investigadores desarrollaron un nuevo método para la formación de enlaces C-N regioselectivos en arenas utilizando interacciones no covalentes para guiar cationes radicales. Este enfoque proporciona acceso directo a las ortofenilendiaminas, cruciales para la síntesis de diazoles médicamente relevantes.

Área de la Ciencia:

Química orgánica
Metodología sintética
Química medicinal

Sus antecedentes:

La formación directa de enlaces arenos C-N a partir de enlaces C-H es crucial en la síntesis orgánica.
Las reacciones mediadas por radicales que involucran radicales centrados en N han avanzado en este campo.
El control regional sigue siendo un desafío importante, a menudo dando lugar a mezclas isoméricas.

Objetivo del estudio:

Desarrollar una nueva estrategia para la formación de enlaces regioselectivos C-N en la posición arene orto.
Utilizar las interacciones no covalentes para controlar la selectividad posicional en las reacciones radicales.
Proporcionar un acceso eficiente a las ortofenilendiaminas y sus derivados.

Principales métodos:

Diseño de un sustrato aniónico (anilina protegida con sulfamato) para interactuar con los cationes radicales entrantes.
Utilizando interacciones no covalentes atractivas para dirigir el catión radical a la posición orto areno.
Escisión telescópica del grupo sulfamato después de la aminación para obtener ortofenilenodiaminas.

Principales resultados:

Se ha logrado una alta regioselectividad para la ortoaminación de arenas.
Se ha demostrado la síntesis de ortofenilendiaminas libres y monoalquiladas.
Se han sintetizado con éxito benzimidazoles y benzotriazoles no simétricos y selectivamente alquilados.

Conclusiones:

Las interacciones no covalentes pueden controlar efectivamente la selectividad posicional en las reacciones radicales.
El método desarrollado ofrece una ruta concisa a las valiosas ortofenilenodiaminas.
Esta estrategia facilita el acceso a compuestos heterocíclicos médicamente relevantes.

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