Mitsunobu Approach to the Synthesis of Optically Active α,α-Disubstituted Amino Acids

Chiral tertiary α-hydroxy esters of known stereochemical configuration were transformed to α-azido esters by Mitsunobu reaction with HN₃. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe₃). Complete inversion of configuration was observed at the α-carbon. Several α,α-disubstituted amino acids were synthesized in high overall chemical yield and optical purity.