TANDEM PROTOCOL FOR THE STEREOSELECTIVE SYNTHESIS OF DIFFERENT POLYFUNCTIONAL BETA-AMINO ACIDS AND 3-AMINO-SUBSTITUTED CARBOHYDRATES

Conjugate addition of homochiral amidocuprates or lithium amides based on (R)-N-(1-phenylethyl)(trimethylsilyl)amine to alpha,beta-unsaturat ed esters proceeds stereoselectively and allows the synthesis of beta- amino acids. Trapping of the intermediate ester enolate with D2O affor ds the corresponding deuterated compounds. anti-alpha-Alkyl-beta-amino acids are obtained stereoselectively after transmetalation of the lit hium/copper ester enolate to the titanium ester enolate and trapping w ith carbon electrophiles. Both diastereomers of beta-homothreonine, ot her precursors of 3-amino-substituted carbohydrates, and stereoselecti vely in position 2 deuterated analogues are formed from enantiomerical ly pure gamma-alkoxy-substituted enoates. The product distribution obs erved is complementary to published results regarding 1,4-addition to gamma-silyloxy-substituted enoates. The anti/syn selectivity can be ex plained by assuming transition state geometries where the delivery of the nitrogen nucleophile is controlled by lithium ''chelation'' betwee n reagent and substrate. In one case the product configuration can be controlled by the reagent irrespective of the substrate stereochemistr y; in other cases the topicity of the addition is complementary to pub lished results. For instance, erythro- or threo-configured 2,3-dideoxy -3-aminopentoses are accessible via this route.