Lanthanide-Crown Ether Mixtures as Chiral NMR Shift Reagents for Amino Acid Esters, Amines and Amino Alcohols

Abstract

Two chiral crown ethers, 2,3:4,5‐bis[1,2‐(3‐phenylnaphtho)‐1,6,9,12,15,18‐hexaoxacycloeicosa‐2,4‐diene and 1,2:5,6‐di‐O‐isopropylidene‐3,4‐[(tert‐butylbenzenediyl)bis(oxyethoxy)ethyl‐D‐mannitol, were evaluated as organic‐soluble chiral NMR resolving agents. The crown ethers are useful resolving agents for protonated amino acid esters, amines and amino alcohols. Enantiodiscrimination with the crown ethers is better in methanol than in acetonitrile or chloroform. Organic‐soluble lanthanide tetrakis(β‐diketonate) anions, which are formed in solution by mixing a lanthanide tris(β‐diketonate) and silver β‐diketonate, can be added to crown–substrate mixtures to enhance the enantiomeric resolution. The lanthanide‐induced enhancement occurs because the enantiomers of the substrate have different association constants with the crown ethers. The enantiomer that associates less favorably with the crown ether is more available to complex with the lanthanide. © 1997 by John Wiley & Sons, Ltd.

Chiral recognition mechanism studies of Tyr‐Arg‐Phe‐Lys‐NH2 tetrapeptide on crown ether‐based chiral stationary phase

“…This behavior indicates on some sort of intermolecular binding, possibly a hydrogen bonding between tetrapeptide 1 and crown ether selector. This assumption is supported by older studies, 28 where shielding effect has been observed for amino acid complexes upon hydrogen bonding with CR (+) selector. However, according to the near identical proton chemical shift differences (ΔΔδ ( llll ‐ dddd ) ~ 0) of formed complexes between llll and dddd enantiomers of tetrapeptide 1 , represented in Table 2, it could be speculated that both enantiomers undergo similar (non‐enantioselective) hydrogen bonding pattern between protonated ε‐NH 2 group in Lys moiety and the oxygens of crown ether selectors.…”

Enantioselective Recognition of Racemic Amino Alcohols in Aqueous Solution by Chiral Metal‐Oxide Keplerate {Mo132} Cluster Capsules

“…Enantiopurity of amino alcohols is important in this context as (S)-propranolol is an active beta-blocker, whereas the (R)-isomer is ineffective in this application but has utility as a potential contraceptive. [24] A universal noncovalent chiral shift reagent for the determination of relative configuration by NMR spectroscopy does not exist and the chiral recognition of amino alcohols has been achieved using several chiral shift reagents, including arylcarboxylic acids, [25][26][27] atropisomers, [28] calixarenes/ resorcinarenes, [29][30][31][32][33][34][35][36] cyclodextrins, [37] crown ethers, [38][39][40] phosphorous-containing reagents, [41][42][43][44] and metallocomplexes, [45,46] amongst others. [47][48][49][50] The separation of amino alcohols has been almost exclusively limited to organic solvents except for resorcinarene and cyclodextrin hosts which have displayed separation in aqueous media.…”