Asymmetric α-C-H Allylic Alkylation of α-Amino Acid Esters by Synergistic Carbonyl/Iridium Catalysis

The efficient and stereoselective construction of chiral quaternary α-amino acids bearing two contiguous stereocenters remains a significant synthetic challenge. Herein, we report a cooperative pyridoxal/iridium catalytic system that enables the direct, branched-selective asymmetric α-C-H allylic alkylation of N-unprotected α-amino acid esters. This transformation merges carbonyl catalysis with iridium catalysis, where the pyridoxal catalyst promotes α-C-H activation to form a nucleophilic α-amino carbanion, and the iridium catalyst generates an electrophilic π-allyl-Ir intermediate. The synergistic interplay of these two catalytic cycles affords quaternary α-amino acid esters containing two contiguous stereocenters in excellent yields (up to 98%), high diastereoselectivity (up to 19:1 dr), and outstanding enantiocontrol (up to 99% ee). This synergistic catalysis strategy provides an efficient and practical approach for constructing chiral quaternary α-amino acids.