Large scale enantiomeric synthesis, purification, and characterization of ω-unsaturated amino acids via a Gly-Ni(II)-BPB-complex

Abstract

The enantiomeric syntheses of ω-unsaturated amino acids and β-substituted ω-unsaturated amino acids were accomplished by using Gly-Ni-2[ N-( N′-benzylprolyl)amino]benzophenone (BPB) as a chiral auxiliary. The synthesis provides excellent yields and high diastereoselectivities. The product crystallization followed by isomer epimerization strategy makes the reaction practical and useful for large-scale preparations. Dialkylation of the Ni(II)-complex, which was designed for mechanistic considerations, revealed that high diastereoselectivity is obtained due to the thermodynamic conformational stability of the Ni(II)-complex. The assignment of absolute configuration was accomplished by NMR, which is supported by corresponding X-ray structure and optical rotation data. Both enantiomerically pure amino acids can be synthesized in this alkylation–hydrolysis two-step strategy in multi gram scales.