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Reacción de Povarov enantioselectiva de tres componentes catalizada por el ácido de Chiral Brønsted
Hua Liu1, Guillaume Dagousset, Géraldine Masson
1Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
Journal of the American Chemical Society
|April 2, 2009
Resumen
Una nueva reacción de Povarov de tres componentes que utiliza ácido fosfórico quiral sintetiza de manera eficiente las tetrahidroquinolinas cis-2,4-disubstituidas. Este método permite la síntesis más corta reportada de torcetrapib, logrando altos rendimientos y pureza enantiomérica.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- Síntesis asimétrica de síntesis.
Sus antecedentes:
- Las tetrahidroquinolinas son importantes andamios heterocíclicos en la química medicinal.
- La síntesis eficiente y enantioselectiva de las tetrahidroquinolinas sustituidas sigue siendo un desafío.
Objetivo del estudio:
- Desarrollar una nueva reacción de Povarov de tres componentes para sintetizar tetrahidroquinolinas cis-2,4-disubstituidas.
- Para demostrar la utilidad de esta reacción en la síntesis más corta de torcetrapib.
Principales métodos:
- Una reacción de tres componentes que involucra aldehídos, anilinas y bencilo N-vinilcarbamato.
- Se utilizaron 0,1 equivalentes de un catalizador quiral de ácido fosfórico.
- Purificación y caracterización de los productos de tetrahidroquinolina resultantes.
Principales resultados:
- Se obtienen buenos rendimientos de tetrahidroquinolinas cis-2,4-disubstituidas.
- Se obtuvieron excelentes excesos enantioméricos para los productos.
- Desarrolló la síntesis más corta reportada de torcetrapib.
Conclusiones:
- La reacción de Povarov de tres componentes desarrollada es altamente eficiente y enantioselectiva.
- Esta metodología proporciona una ruta simplificada a los valiosos derivados de la tetrahidroquinolina.
- La reacción es aplicable a la síntesis de agentes farmacéuticos complejos como el torcetrapib.
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