The Mannich reaction of malonates with simple imines catalyzed by bifunctional cinchona alkaloids: Enantioselective synthesis of β-amino acids

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 β-ketoesters. The synthetic value of this new reaction is demonstrated in the establishment of a convergent enantioselective route toward the biologically important β-amino acids under mild and air- and moisture-tolerant conditions. Copyright © 2006 American Chemical Society.