Lanthanide shifts reagents, in NMR

Paramagnetic Relaxation Reagents. Alternatives or Compliments to Lanthanide Shift Reagents in NMR Spectral Analysis, G. C. Levy and R. A. Ko-moroski, J. Amer. Chem. Soc., 96,678 (1974). 

While the coordination chemistry of lanthanide ions in water is extensive, it is of course not limited to this solvent. In the 1970s, considerable interest developed in the synthesis of lanthanide ion complexes soluble in apolar solvents for their use as lanthanide shift reagents in NMR spectroscopy. Typically, such complexes were neutral and based on chelating 1,3-diketonate ligands, one of their attractive features being that not only did they cause normally overlapping resonances to be spread out and resolved but that they could readily be prepared from optically active ligands and thus used to... 

Reuben J 1973 Paramagnetic lanthanide shift reagents in NMR spectroscopy principles, methodology and applications. Prog Nuc Magn Res Spec 9 1-70... 

Flockhart, B.D., Lanthanide Shift Reagents in NMR Spectroscopy, Crit. Rev. Anal. Chem., 1976, p. 69. Atta-ur-Rahman, NMR Basic Principles, Springer, New York, 1986. 

Differential stability of these solvates has also been demonstrated by NMR through use of an achiral lanthanide shift reagent in conjunction with TFAE. Incremental addition of Eu(fod>3 to a solution of (R)-TFAE and the dinitrolactone shifts the resonances of the (5)-enantiomer more rapidly downfield than those of the (/ )-enantiomer. Nonequivalence increase in this manner arises by a preferential disruption of the least stable R, S) solvate. In the case of the nonnitrated parent, addition of the LSR gradually attenuates nonequivalence, as both solvates (of approximately equal stability) are equally disbanded. 

The NMR spectra of most of the lanthanide shift reagents in solution involve rapid chemical exchange. In many situations one has 1 2 and 1 1 adducts and free ligand in solution. The observed lanthanide induced shift, S is the sum of two contributions... 

Metal enolates found varied application in chemical analysis. An outstanding group are certain lanthanide enolates used as shift reagents in NMR spectroscopy. The analytical methods discussed in Section IV are based on formation of a metal enolate for separation, detection, identification and determination of metal ions or the use of a metal enolate as ancillary reagent to improve analytical quality. Of special relevance in analytical chemistry are the metal /3-diketonates, M(dik) , derivatived from deprotonated /3-diketones (dikH),... 

J. Reuben, in Progress in Nuclear Magnetic Resonance Speetroscopy , Vol. 9, Pt. 1 Lanthanide Shift Reagents m NMR Spectroscopy Principles, Methodology and Applications , Pergamon Press, Oxford, 1973. 

By the reaction of theenolatc of camphor with carboxylic acid esters or chlorides, 1,3-diketones [better formulated as enols. such as (hydroxymethylene)camphor] are obtained. When trifluo-roacetic acid or heptafluorobutanoic acid are used, the corresponding diketones (abbreviated as tfc or hfc, respectively) have been successfully used as ligands for lanthanides and these are used as chiral shift reagents in NMR spectroscopy12. The complex Eu(hfc)3 [derived from ( + )-camphor)] 3 was used as a chiral catalyst for enantioselective Diels-Alder-type cycloadditions of aldehydes to dienes (Section D.l.6.1.1.1.2.4.). 

FIGURE 14 Molecular structures of two commonly used lanthanide shifts reagents in H nuclear magnetic resonance (NMR) spectoscopy. 

The use of shift reagents in NMR, outlined in Section 12.5.1, which show that unpaired electron density in both transition metal and lanthanide complexes can be felt by molecules outside the coordination sphere. 

Sherry AD and Geraldes CFGC (1989) Shift reagents in NMR spectroscopy in lanthanide probes. In-. Biinzli J-CG and Chopin GR (eds) Life, Chemical and Earth Sciences, Theory and Practice, Amsterdam Elsevier. 

Clobazam (54, X = Cl) and related compounds (X = H, X = CF3) exist in the dioxo tautomeric form [80JHC551,87JCS(P2)1071], as do the analogous pyrazolo[3,4-h][l,4]diazepinediones (89JHC949). Tliese conclusions were mainly based on careful NMR studies including the use of lanthanide shift reagents (LSR). 

H-NMR spectroscopy can be used to determine alkenesulfonates in mixtures [115]. Under normal conditions, 1-alkenesulfonate shows a signal separated from the other positional isomers [122]. Moreover, the utilization of a lanthanide shift reagent makes possible even the separation of the signals of isomeric alkenesulfonic acids and hydroxyalkanesulfonic acids as their methyl esters [124]. 13C-NMR spectroscopy, which is not as quantitative, simply gives the cis/trans ratio of the main positional isomer. 

A closely related method does not require conversion of enantiomers to diastereomers but relies on the fact that (in principle, at least) enantiomers have different NMR spectra in a chiral solvent, or when mixed with a chiral molecule (in which case transient diastereomeric species may form). In such cases, the peaks may be separated enough to permit the proportions of enantiomers to be determined from their intensities. Another variation, which gives better results in many cases, is to use an achiral solvent but with the addition of a chiral lanthanide shift reagent such as tris[3-trifiuoroacetyl-Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for examples, alcohols, carbonyl compounds, amines, and so on. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

The conformational preference of the monosulfoxides of 1,2-, 1,3- and 1,4-dithianes (179-181) were determined by NMR experiments which included variable-temperature studies, double irradiation, solvent effects and the inhuence of lanthanide shift reagents For 179 and 181, the axial conformers were the dominant species in CDjOD, but for 180 the equatorial conformer was in excess. 

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

Figure 2. Dy(P30io)2 is a lanthanide shift reagent commonly used in biological 7Li NMR experiments. The Dy3+ ion has a coordination number of nine with two P3O10 moieties, acting as tetradentate ligands, and one molecule of H2O coordinated in the first coordination sphere up to seven Li+ ions can bind in the second coordination sphere.

Similar differentiation between enantiomers by means of NMR can also be achieved by the use of chiral lanthanide shift reagents (243). Tris-[3-(heptafluoropropylhydroxymethylene)-d-camphorato] -europium was used for the first time (244) for determining the enantiomeric content of benzyl methyl sulfoxide 34. The enantiomeric composition of the partially resolved methyl p-tolyl sulfoxide 41 was estimated using tris-[3-(r-butylhydroxymethylene)-c -camphorato]-europium (245). Another complex of europium, tris-[3-(trifluoro-methylhydroxymethylene)-c -camphorato] europium (TFMC), in contrast to those mentioned above, was effective in the differentiation of various enantiomeric mixtures of chiral sulfinates (107), thiosul-finates (35), and sulfinamides (246). 

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