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4-Perfluoroalquilación y perfluoroarilación C-H selectiva por posición de compuestos heteroaromáticos de seis

Masahiro Nagase¹, Yoichiro Kuninobu^1,2, Motomu Kanai^1,2

¹Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Journal of the American Chemical Society

|May 3, 2016

Resumen

Los investigadores lograron la primera perfluoroalquilación y perfluoroarilación C-H selectiva en 4 posiciones de compuestos heteroaromáticos de seis miembros. Este avance permite la funcionalidad eficiente en las últimas etapas de las moléculas bioactivas.

Área de la Ciencia:

Química orgánica
Química sintética
Química medicinal

Sus antecedentes:

La funcionalización selectiva de los compuestos heteroaromáticos es crucial para el descubrimiento de fármacos.
Los métodos existentes a menudo carecen de regioselectividad o requieren condiciones duras.

Objetivo del estudio:

Desarrollar un nuevo método para la perfluoroalquilación y perfluoroarilación de C-H selectiva en 4 posiciones de compuestos heteroaromáticos de seis miembros.
Para permitir la funcionalización en etapa tardía de moléculas bioactivas con grupos perfluoroalquilo y perfluoroarilo.

Principales métodos:

Se han utilizado reactivos de perfluoroalquilación y perfluoroarilación nucleófilos.
Se utiliza la activación electrofílica de los anillos heteroaromáticos.
Usó un ácido de Lewis estéricamente voluminoso para obstaculizar la posición 2, dirigiendo la regioselectividad.

Principales resultados:

Logró la primera perfluoroalquilación y perfluoroarilación C-H selectiva en 4 posiciones de compuestos heteroaromáticos de seis miembros.
Se han demostrado buenos rendimientos, escalabilidad a escala de gramos y una reacción secuencial sin aislamiento intermedio.
Se ha aplicado con éxito el método a la fase tardía de trifluorometilación de un compuesto bioactivo.

Conclusiones:

Desarrolló un método robusto y regioselectivo para la introducción de grupos perfluoroalquilo y perfluoroarilo en la posición 4 de los heteroaromáticos.
La metodología ofrece una herramienta valiosa para sintetizar moléculas orgánicas fluoradas complejas.
Este enfoque tiene implicaciones significativas para la química medicinal y el desarrollo de fármacos.

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