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Updated: Oct 3, 2026

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Tandem Protocol for the Stereoselective Synthesis of Different Polyfunctional beta-Amino Acids and
Norbert Sewald1, Klaus D. Hiller, Matthias Körner
1Department of Organic Chemistry and Department of Analytical Chemistry, University of Leipzig, Leipzig, FRG.
Abstract:
Conjugate addition of homochiral amidocuprates or lithium amides based on (R)-N-(1-phenylethyl)(trimethylsilyl)amine to alpha,beta-unsaturated esters proceeds stereoselectively and allows the synthesis of beta-amino acids. Trapping of the intermediate ester enolate with D(2)O affords the corresponding deuterated compounds. anti-alpha-Alkyl-beta-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 beta-homothreonine, other precursors of 3-amino-substituted carbohydrates, and stereoselectively in position 2 deuterated analogues are formed from enantiomerically pure gamma-alkoxy-substituted enoates. The product distribution observed is complementary to published results regarding 1,4-addition to gamma-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.
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If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.

