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Published on: February 16, 2020
Vínilo directo organocatalítico y altamente estereoselectivo, con reacción de Mannich
Tian-Yu Liu1, Hai-Lei Cui, Jun Long
1Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Journal of the American Chemical Society
|February 1, 2007
Resumen
Una nueva reacción asimétrica viníloga de Mannich utilizando un organocatalizador quiral permite una síntesis eficiente de valiosos aminoácidos delta. Este método ofrece una alta selectividad y un amplio alcance de sustrato a temperatura ambiente.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- La catálisis asimétrica.
Sus antecedentes:
- La reacción de Mannich es una reacción fundamental de formación de enlaces carbono-carbono en la síntesis orgánica.
- El desarrollo de variantes asimétricas es crucial para acceder a compuestos enantioméricamente puros.
- Las reacciones de Mannich vinílogas asimétricas directas son menos exploradas, especialmente con sustratos difíciles como las alfa, alfa-dicianolefinas.
Objetivo del estudio:
- Para desarrollar la primera reacción directa asimétrica viníloga de Mannich (AVM) de alfa, alfa-dicianolefinas y N-Boc aldiminas.
- Identificar un organocatalisador eficiente y selectivo para esta transformación.
- Demostrar la utilidad de los adutos para la síntesis de ácidos amino delta enantioméricamente puros.
Principales métodos:
- Se utilizó un organocatalisador quiral bifuncional de tiorrea y aminas terciarias.
- Realizó la reacción entre las alfa, alfa-dicianolefinas y las aldiminas N-Boc.
- Condiciones de reacción optimizadas que incluyen la carga del catalizador, la temperatura y el disolvente.
- Estereoquímica del producto analizado mediante cromatografía líquida quiral de alto rendimiento (HPLC).
Principales resultados:
- Logró la primera reacción de Mannich viníloga asimétrica directa de las alfa, alfa-dicianolefinas y las N-Boc aldiminas.
- La reacción procedió con una alta eficiencia (relación sustrato-catalizador de hasta 1000).
- Se ha demostrado una excelente regionalidad y estereoselectividad (generalmente >99% de exceso diastereomérico y 96 a >99.5% de exceso enantiomérico).
- La reacción fue efectiva a temperatura ambiente en una amplia gama de sustratos.
- Los ácidos delta-amino enantioméricamente puros se prepararon suavemente a partir de los aductos de reacción.
Conclusiones:
- Se ha establecido una nueva y altamente eficiente reacción de Mannich viníloga asimétrica directa.
- Un simple organocatalisador quiral bifuncional de tiurea y aminas terciarias es eficaz para esta transformación.
- Esta metodología proporciona una ruta fácil a los ácidos amino delta enriquecidos enantioméricamente, bloques de construcción valiosos en la química medicinal.
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