Asymmetric organocatalytic direct aldol reactions of ketones with alpha-keto acids and their application to the synthesis of 2-hydroxy-gamma-butyrolactones.
J Org Chem
; 72(26): 9905-13, 2007 Dec 21.
Article
en En
| MEDLINE
| ID: mdl-18004868
ABSTRACT
A variety of organocatalysts for the asymmetric direct aldol reactions of ketones with alpha-keto acids were designed on the basis of molecular recognition and prepared from proline and aminopyridines. The organic molecule 8e, derived from proline and 6-methyl-2-amino pyridine, was the best catalyst, affording excellent enantioselectivities (up to 98% ee) for the direct aldol reactions of acetone or 2-butanone with a wide range of alpha-keto acids and for the reactions of various acyclic aliphatic ketones with 3-(2-nitrophenyl)-2-oxopropanoic acid. The aldol adducts could be converted to 2-hydroxy-gamma-butyrolactones by reaction sequences of diastereoselective reduction and lactonization. Experimental and theoretical studies on the transition states revealed that the amide N-H and the pyridine N of the organocatalyst selectively form hydrogen bonds with the keto oxygen and the carboxylic acid hydroxy of the alpha-keto acid, respectively. These two hydrogen-bonding interactions are important for the reactivity and enantioselectivity of the direct asymmetric aldol condensation.
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Base de datos:
MEDLINE
Asunto principal:
4-Butirolactona
/
Prolina
/
Aminopiridinas
/
Cetoácidos
/
Cetonas
Idioma:
En
Revista:
J Org Chem
Año:
2007
Tipo del documento:
Article