Tandem protocol for the stereoselective synthesis of different polyfunctional β-amino acids and 3-amino-substituted carbohydrates

Article abstract of DOI:10.1021/jo980656z

Conjugate addition of homochiral 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-α-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 in position 2 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.