Diastereo- and enantioselective synthesis of α-substituted β-amino acid esters by tandem Michael-addition/α-alkylation with TMS-SAMP as chiral equivalent of ammonia

Article abstract of DOI:10.1055/s-1994-25688

The hetero Michael-addition of (S)-(-)2-methoxymethyl-1-trimethylsilylaminopyrrolidine (TMS-SAMP) to α,β-unsaturated esters 1, followed by α-alkylation of the intermediate esterenolates with various electrophiles yields α-substituted β-hydrazino esters 3 of anti-configuration in good to excellent diastereomeric excesses (de = 63 - ≥96%). Subsequent reductive N-N bond cleavage leads to β-amino acid esters 4 (R¹ = C₆H₁₁) in good yields and high diastereo- and enantiomeric purity (de, ee ≥ 96%). The stereochemistry was confirmed by NMR-spectroscopy and X-ray structure analysis.