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

Abstract

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 (<i>S</i>,<i>S</i>)-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