| Abstract
| - A variety of organocatalysts for the asymmetric direct aldol reactions of ketones with α-keto acids weredesigned on the basis of molecular recognition and prepared from proline and aminopyridines. The organicmolecule 8e, derived from proline and 6-methyl-2-amino pyridine, was the best catalyst, affording excellentenantioselectivities (up to 98% ee) for the direct aldol reactions of acetone or 2-butanone with a widerange of α-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-γ-butyrolactones by reactionsequences of diastereoselective reduction and lactonization. Experimental and theoretical studies on thetransition states revealed that the amide N−H and the pyridine N of the organocatalyst selectively formhydrogen bonds with the keto oxygen and the carboxylic acid hydroxy of the α-keto acid, respectively.These two hydrogen-bonding interactions are important for the reactivity and enantioselectivity of thedirect asymmetric aldol condensation.
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