Synthesis of unnatural α-amino acid derivatives via a three-component coupling method utilizing an allylpalladium umpolung

Highly substituted unnatural a-amino esters, for example, ethyl 3-alkyl-4-(aryl or vinyl)-2-(N-4-methoxyphenylamine)pent-4-enoates were prepared in a regiocontrolled and diastereoselective manner via Pd(II)-catalyzed three-component coupling of boronic acids and allenes with ethyl iminoacetate relying on the umpolung of the traditional electrophilicity of mono-pi-allylpalladium complexes. The 2-aminopent-4-enoates were subjected to N-allylation and intramolecular ring-closing metathesis to afford tetrahydropyridines featuring an alpha-amino ester group.