Asymmetric synthesis of amino acids

Conjugate addition of enantiomerically pure amidocuprates or lithium amides based on (R)-N-(1-phenylethyl)-(trimethylsilyl)amine to α,β-unsaturated esters proceeds stereoselectively and allows the synthesis of β-amino acids. Trapping of the intermediate ester enolate with D2O affords the corresponding deuterated compounds. anti-Alkyl-β-amino acids are obtained stereoselectively after transmetalation of the lithium/copper ester enolate to the titanium ester enolate and trapping with carbon electrophiles. Both diastereomers of β-homothreonine, other precursors of 3-amino-substituted carbohydrates, and stereoselectively deuterated analogues are formed from enantiomerically pure γ-alkoxy-substituted enoates. The product distribution observed is complementary to published results regarding 1,4-addition to γ-silyloxy-substituted enoates. The anti/syn selectivity can be explained by assuming transition state geometries where the delivery of the nitrogen nucleophile is controlled by lithium "chelation" between reagent and substrate. In one case the product configuration can be controlled by the reagent irrespective of the substrate stereochemistry; in other cases the topicity of the addition is complementary to published results. For instance, erythro- or threo-configured 2,3-dideoxy-3-aminopentoses are accessible via this route.

Tandem Protocol for the Stereoselective Synthesis of Different Polyfunctional β-Amino Acids and 3-Amino Substituted Carbohydrates
N. Sewald, K. D. Hiller, M. Körner, M. Findeisen
J. Org. Chem., 63 (1998) 7263-7274.

Moreover, suitably protected enantiomerically pure β2-amino acids, homologues of proteinogenic α-amino acids, were synthesized from the common chiral precursor, tert-butyl succinyloxazolidinone.

Chiral Succinate: A precursor for enantiomerically pure β2-amino acids
A. Stončius, M. Nahrwold, N. Sewald
Synthesis, (2005) 1829-1837.

People involved:
Dr. Klaus D. Hiller, Dr. Matthias Körner, Markus Nahrwold, Dr. Arvydas Stončius


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