Determination of Enantiomer Purity ofβ- andγ-Amino Acids by NMR Analysis of Diastereoisomeric Palladium Complexes

Abstract

Like α-amino acids, β- and γ-amino acids form spirobicyclic complexes (see 2 and 3) by reaction with the chiral di-μ-chlorobis{2-[1-dimethylamino-ϰN)-ethyl]phenyl-ϰC}dipalladium complexes 1 under basic conditions (Scheme 1 and X-ray structures in Fig. 1). The diastereoisomeric complexes formed with mixtures of enantiomers of either the amino acids or the dichloro-dipalladium complexes give rise to marked chemical-shift differences in the 1H- and 13C-NMR spectra (Figs. 2 – 4) to allow determination of the enantiomer purities. A simple procedure is described by which β- and γ-amino acids (which may be generated in situ from Boc- or Fmoc-protected precursors) are converted to the Pd complexes and subjected to NMR measurements. The effects of solvent, temperature, and variation of the aryl group in the chiral derivatizing Pd reagent are described (Figs. 4 and 5). The methyl esters of β-amino acids can also be employed, forming diastereoisomeric chloro[(amino-ϰN)aryl-ϰC][(amino-ϰN)alkanoate]palladium complexes 6 for determining enantiomer ratios (Scheme 6). The new method has great scope, as demonstrated for β2-, β3-, β2,3-, β2,2,3-, γ2-, γ3-, γ4-, and γ2,3,4-amino acid derivatives.