Asymmetric Synthesis of α‑Allyl-α-Aryl α‑Amino Acids by Tandem Alkylation/π-Allylation of α‑Iminoesters

The
first asymmetric synthesis of α-allyl-α-aryl α-amino
acids by means of a three-component coupling of α-iminoesters,
Grignard reagents, and cinnamyl acetate is reported. Notably, the
enolate from the tandem process provides a much higher level of reactivity
and selectivity than the same enolate generated via direct deprotonation,
presumably due to differences in the solvation/aggregation state.
A novel method for removal of a homoallylic amine protecting group
delivers the free amine congeners. The α-allyl group offers
a means to generate further valuable α-amino acid structures
as exemplified by ring closing metathesis to generate a higher ring
homologue of α-aryl-proline.