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Lactonización C-H enantioselectiva de metileno no activado dirigida por ácidos carboxílicos

Marco Cianfanelli¹, Giorgio Olivo¹, Michela Milan¹

¹QBIS Research Group, Institut de Química Computacional i Catàlisi (IQCC), and Departament de Química , Universitat de Girona , Campus Montilivi , Girona E-17071 , Catalonia , Spain.

Journal of the American Chemical Society

|December 28, 2019

Resumen

Este estudio introduce un nuevo método de oxidación C-H catalizado por manganeso para crear gamma-lactonas quirales con una selectividad excepcional. La reacción controla eficientemente el sitio, el enantio y la quimioselectividad utilizando grupos directores simples de ácido carboxílico y peróxido de hidrógeno.

Área de la Ciencia:

Química orgánica
Catálisis
Metodología sintética

Sus antecedentes:

La oxidación asimétrica C-H es un desafío debido a las dificultades para controlar la selectividad.
Los sistemas no enzimáticos luchan con la selectividad del sitio, la enantioselectividad y la quimioselectividad.
La discriminación de los enlaces enantiotópicos C-H y la prevención de la sobreoxidación siguen siendo obstáculos importantes.

Objetivo del estudio:

Desarrollar un método de oxidación C-H asimétrico altamente selectivo para sintetizar las gamma-lactonas.
Para superar los desafíos en la selectividad del sitio, la enantioselectividad y la quimioselectividad en sistemas no enzimáticos.
Establecer un sistema catalítico predecible y versátil para la síntesis de moléculas complejas.

Principales métodos:

Se utilizó una reacción de oxidación C-H catalizada por manganeso (Mn).
Se emplean ácidos carboxílicos como grupos de dirección para la coordinación del sustrato.
Se utiliza peróxido de hidrógeno como oxidante y como aditivo de ácido de Brønsted.
Diseño de catalizador investigado para modular la discriminación de enlaces diastereotópicos C-H.

Principales resultados:

Se obtiene un alto exceso enantiomérico (hasta el 99%) en la formación de gamma-lactona.
Se ha demostrado una excelente selectividad del sitio gamma a través de la coordinación del ácido carboxílico con el complejo Mn.
Se ha demostrado una selectividad predecible del sitio para sustratos con gamma-metileno no equivalente.
Sintetizó con éxito un complejo biciclo tetrahidroxilado [3.3.1] nonano, estableciendo cinco estereocentros en un solo paso con 96% ee.

Conclusiones:

Desarrolló un método robusto y eficiente para la oxidación asimétrica de C-H a través de la catalización de Mn.
El método ofrece un alto control de la selectividad, abordando desafíos de larga data en el campo.
La previsibilidad de la reacción y su amplia aplicabilidad se demuestran a través de la síntesis compleja, destacando su potencial en la síntesis orgánica.

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