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. 2006 May 10;128(18):6048-9.
doi: 10.1021/ja060716f.

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

Jun Song  1 , Yi Wang, Li Deng
Affiliations

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

Jun Song et al. J Am Chem Soc. .

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.

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Figures

Figure 1
Figure 1
C6′ or C9 thiourea cinchona alkaloid derivatives.
Scheme 1
Scheme 1
Synthesis of N-Boc-β-amino acids
See this image and copyright information in PMC

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    1. Only one Mannich reaction with malonates and an activated N-tosyl-α-imino ester in 39–87% ee has been reported: Marigo M, Kjærsgaard A, Juhl K, Gathergood N, Jørgensen KA. Chem Eur J. 2003;9:2359.

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