Lanthanide chemical shift reagents

The synthesis of lanthanide chemical shift reagents has been the objective of many groups owing to their effect on NMR spectra simplification. A drawback of the commonly used reagents is their sensitivity to water or acids. Tris(tetraphenylimido diphosphinatojpraseodymium [Pr(tpip)3] has been developed as a CSR for the analysis of carboxylic acids.17 Furthermore, it has been found that dinuclear dicarboxylate complexes can be obtained through reactions with ammonium or potassium salts of carboxylic acids, and these compounds can be used to determine the enantiomer composition of carboxylic acids.18... 

The same principle is involved in the use of chiral lanthanide chemical shift reagents for the determination of enantiotopic purity [44]. 

As a matter of historical introduction it is noted that the first application (4) of a paramagnetic lanthanide chemical shift reagent involved the simplification of the proton NMR spectrum of cholesterol by means of Eu(dpm)3-2py. The applications and development of these valuable reagents are the subject of a book (5) and a recent review. (6)... 

Lagrangian multipliers, 227, 228 Lanthanide chemical shift reagents, 13 LCAO, 229... 

It has been long appreciated that a chiral environment may differentiate any physical property of enantiomeric molecules. NMR spectroscopy is a sensitive probe for the occurrence of interactions between chiral molecules [4]. NMR spectra of enantiomers in an achiral medium are identical because enantiotopic groups display the same values of NMR parameters. Enantiodifferentiation of the spectral parameters (chemical shifts, spin-spin coupling constants, relaxation rates) requires the use of a chiral medium, such as CyDs, that converts the mixture of enantiomers into a mixture of diastereomeric complexes. Other types of chiral systems used in NMR spectroscopy include chiral lanthanide chemical shift reagents [61, 62] and chiral liquid crystals [63, 64). These approaches can be combined. For example, CyD as a chiral solvating medium was used for chiral recognition in the analysis of residual quadrupolar splittings in an achiral lyotropic liquid crystal [65]. 

Achiral lanthanide shifting reagents may be used to enhance the anisochrony of diastereomeric mixtures to facilitate their quantitative analysis. Chiral lanthanide shift reagents are much more commonly used to quantitatively analyze enantiomer compositions. Sometimes it may be necessary to chemically convert the enantiomer mixtures to their derivatives in order to get reasonable peak separation with chiral chemical shift reagents. 

Barriers for interconversion between BC-3 and its enantiomer, BC-7, have been calculated. Passage through either a BC-5 or a BC-1 conformation, are calculated to be 5.0 kcal mol and 6.7 kcal mol , respectively. The small barriers allow for a rapid pseudorotation between BC-3 and BC-7, even at low temperatures, and account for the symmetric spectra. NMR results on oxocane-2,2,7,7-d4 have allowed a definitive assignment for the H and C chemical shifts. Lanthanide-induced shift reagents provide compelling proof, that the lowest energy conformations are BC-3 and BC-7. 

Silver(i)-catalysed isomerization of the substituted tricyclic hydrocarbons (533) takes place with methyl migration. Compound (534 R = Me) was synthesized independently. The stereochemistry of (534 R = Ph) was deduced by the effect of lanthanide n.m.r. chemical shift reagents on the epoxide obtained from (534 R = Ph). 

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