The Mannich Reaction of Malonates with Simple Imines Catalyzed by Bifunctional Cinchona Alkaloids:  Enantioselective Synthesis of β-Amino Acids

The first efficient, direct asymmetric Mannich reactions with malonates and N-Boc aryl and alkyl imines by cooperative hydrogen-bonding catalysis with a cinchona alkaloid bearing a thiourea functionality are described.

Abstract

We describe the first efficient, direct asymmetric Mannich reactions with malonates and N-Boc aryl and alkyl imines by cooperative hydrogen-bonding catalysis with a cinchona alkaloid bearing a thiourea functionality. We have also extended the scope of this reaction to beta-ketoesters. The synthetic value of this new reaction is demonstrated in the establishment of a convergent enantioselective route toward the biologically important beta-amino acids under mild and air- and moisture-tolerant conditions.