Construction of Chiral α‑Amino Quaternary Stereogenic Centers via Phase-Transfer Catalyzed Enantioselective α‑Alkylation of α‑Amidomalonates

An
efficient enantioselective synthetic method for α-amido-α-alkylmalonates
via phase-transfer catalytic α-alkylation was successfully developed.
The α-alkylation of α-amidomalonates under phase-transfer
catalytic conditions (50% KOH, toluene, −40 °C) in the
presence of (S,S)-3,4,5-trifluorophenyl-NAS
bromide afforded the corresponding α-amido-α-alkylmalonates
in high chemical yields (up to 99%) and optical yields (up to 97%
ee), which could be readily converted to versatile chiral intermediates
bearing α-amino quaternary stereogenic centers. The synthetic
potential of this methodology was demonstrated via the synthesis of
chiral azlactone, oxazoline, and unnatural α-amino acid.