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

Abstract

Dedicated to Professor Günter Helmchen on the occasion of his 60th birthday Like a-amino acids, b-and g-amino acids form spirobicyclic complexes (see 2 and 3) by reaction with the chiral di-m-chlorobis{2-[1-dimethylamino-kN)-ethyl]phenyl-kC}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 1 H-and 13 C-NMR spectra (Figs. 2 ± 4) to allow determination of the enantiomer purities. A simple procedure is described by which b-and g-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 b-amino acids can also be employed, forming diastereoisomeric chloro[(amino-kN)aryl-kC][(amino-kN)alkanoate]palladium complexes 6 for determining enantiomer ratios (Scheme 6). The new method has great scope, as demonstrated for b 2 -, b 3 -, b 2,3 -, b 2,2,3 -, g 2 -, g 3 -, g 4 -, and g 2,3,4 -amino acid derivatives.

3-{[(Benzyloxy)carbonyl]amino}butanoic acid

“…For bond-length data, see: Allen et al (1987). For structures of related metallo-organic compounds, see: Bryan et al (1961); Bö hm & Seebach (2000); Gross & Vahrenkamo (2005).…”

Self-Assembly Motifs of Water in Crystals of Palladium β-Amino Acid Complexes Influenced by Methyl Substitution on the Amino Acid Backbone

“…This is somewhat surprising since a beta-amino acid should form a stable 6-membered ring chelate with metals, coordinating through the carboxylate O atom and the amino N atom. There are a number of β-amino acid complexes of first-row transition metals such as Co and Cu [9][10][11][12][13][14][15][16] but many fewer examples of heavier metals such as Pd and Pt [17][18][19]. It is not surprising that the hydrogen-bonding (H-bonding) capabilities of amino acids play a large role in the solid-state structures of the their metal complexes.…”

Enantiomeric Discrimination of Isoxazoline Fused β‐amino Acid Derivatives using (18‐Crown‐6)‐2,3,11,12‐tetracarboxylic Acid as a Chiral NMR Solvating Agent

“…1 One system involves the use of a water-soluble Eu(III) complex with propylenediaminetetraacetate. 17 Neither of these metal complexes is commercially available. The b-amino acid displaces the bridging chloro ligands in the dimer to form a monopalladium complex.…”

“…The b-amino acid displaces the bridging chloro ligands in the dimer to form a monopalladium complex. 17 Neither of these metal complexes is commercially available. Also, europium shift reagents are often limited in utility because of paramagnetic broadening that occurs in the NMR spectrum.…”