Asymmetric Mannich reactions of α-ketoesters catalyzed through noncovalent interactions: Differences between pyruvates and substituted pyruvates in the formation of nucleophilic species

Diastereo- and enantioselective Mannich reactions of substituted pyruvates or α-ketoester derivatives that are larger than 2-oxopropanoates catalyzed by a tertiary amine derivative bearing functional groups that can form hydrogen bonds are described. γ-Amino β-substituted α-ketoesters were obtained with high diastereo- and enantioselectivities. Whereas substituted pyruvates did not react with imines in the presence of the catalyst system composed of a primary amine derivative and an acid that was previously used for the catalysis of Mannich reactions of ethyl pyruvate via the formation of an enamine, the use of the tertiary amine derivative bearing functional groups that can form hydrogen bonds enabled the activation of substituted pyruvates, leading to the formation of the desired Mannich reaction products. • Catalytic diastereo- and enantioselective Mannich reactions of α-ketoesters • Mannich reactions of α-ketoesters larger than 2-oxopropanoates • Formation of enantiomerically enriched γ-amino β-substututed α-ketoesters • Tertiary amine derivative bearing hydrogen bond-forming functional groups as catalyst • Deuteration experiments on simple and substituted pyruvates to understand mechanisms