Enantioselective synthesis of 2-substituted 3-aminopropanoic acid (β-alanine) derivatives which are β-analogues of aromatic amino acids

Abstract

3-Aminopropanoic acid derivatives with a phenyl, 4-hydroxyphenyl, benzyl or indol-3-yl substituent at C-2 can be prepared enantioselectively by routes involving electrophilic attack of synthetic equivalents of [H₂NCH₂]⁺ upon enolates derived from chiral 3-acyl-1,3-oxazolidin-2-ones. tert-Butyl bromoacetate may be used as the electrophile, with subsequent introduction of nitrogen through the Curtius reaction, using the sequence of reagents (i) CF₃CO₂H; (ii) (PhO)₂P(O)N₃, Et₃N, PhCH₂OH; alternatively, direct electrophilic reaction with 1-[N-(benzyloxycarbonyl)aminomethyl]benzotriazole 4c or benzyl N-(acetoxymethyl)carbamate 2d introduces a protected aminomethyl group in a single step.