Asymmetric Synthesis with Chiral β-Lactams. α-Substituted Aromatic α-Amino Acids and Their Derivatives through Highly Stereoselective Alkylations

A novel route to optically pure α-alkylated aromatic α-amino acids and their dipeptide derivatives was developed through the asymmetric alkylation at the C-3 position of a chiral β-lactam 1 followed by the reductive cleavage of the alkylated β-lactams 2. The stereochemical course of the reaction is effectively controlled by the chiral center at the C-4 position of the β-lactam. This novel asymmetric alkylation was successfully applied for the synthesis of (S)-α-methyl-DOPA via a chiral β-lactam 4, which was synthesized by the asymmetric [2 + 2] cycloaddition of a chiral ketene to an imine.