Enantioselective alkylation and protonation of prochiral enolates in the asymmetric synthesis of β-amino acids

Achiral 1-benzoyl-3-methylperhydropyrimidin-4-one () was deemed a useful, potential precursor for the enantioselective synthesis of α-substituted β-amino acids. Pyrimidinone was prepared from inexpensive β-aminopropanoic acid in 62% overall yield. Prochiral enolate derivative was alkylated in good yield and moderate enantioselectivity in the presence of chiral amines , , , or (−)-sparteine. The enantioselectivity of the alkylation process is highest in toluene as the solvent and in the presence of lithium bromide as additive. The racemic alkylated derivatives and were readily metallated with LDA to give prochiral enolates and , that were reprotonated with novel chiral phenolic acids , , , and in moderate enantioselectivity in the case of and good enantioselectivity in the case of . The acid (6N HCl) hydrolysis of enantioenriched and proceeded in good yield and without racemization to afford α-alkyl-β-amino acids and , respectively.