Achiral shift reagents

RCHDOH, can be determined by the relative chemical shift of the carbinyl protons in the corresponding (—)-camphanate esters in the presence of the (achiral) shift reagent Eu(dpm)3. 

V. COUPLING OF ACHIRAL SHIFT REAGENTS TO CHIRAL DERIVATIZING AND SOLVATING AGENTS... 

The distinction between enantiomeric species is normally made by the use of a chiral shift reagent (Section F.4). However, it has been reported that in certain circumstances sueh a distinction can be achieved with an achiral shift reagent. (497) Enantiomeric shift differences AA<5 are induced by Ln(fod)3 for partly resolved alkylamines (Fig. 10). The values... 

The resolution of mixtures of steroidal diastereomers using Eu(dpm)3 has been reported by Joseph-Nathan et al. (1972). More recently DePuy et al. (1976) demonstrated that Eu(fod)3 resolves not only the diastereomers of 2-methoxy-3-methyl-pentane but also the additional pairs of diastereomers obtained by monodeuteration at position 4. It should be emphasized that spectral resolution of diastereomeric mixtures by achiral shift reagents may occur by two possible mechanisms different shifts in the adducts and different association constants. If the latter is the dominant mechanism the chemical shift difference induced by the reagent will have a maximum at certain reagent concentration and will decrease with increasing the concentration. 

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. 

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. 

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 development of achiral lanthanide shift reagents preceded that of chiral LSRs. It was demonstrated86 in 1969 that paramagnetic Eu(thd)3 and Eu(fod)3 (Tablet), as well as the... 

Europium(III), and particularly ytterbium(III) shift reagents, induce downfield proton resonance shifts while the praseodymium(III) analogs cause upfield shifts. Lanthanide chelates of fluorinated /3-diketonates are more soluble in organic solvents, and they form more stable association complexes with donor molecules, than do LSRs with nonfluorinated ligands. Thus Eu(fod)3 is the preferred achiral LSR for weak nucleophiles89. 

In 1975, it was reported that while lanthanide shift reagents could not be used directly to simplify the NMR spectra of alkenes, when coupled with silver salts substantial shifts could be induced.232 Since then, a number of studies have reported the use of both chiral and achiral lanthanide(III)-silver(I) binuclear shift reagents,233-237 where the ligands were generally fluorinated /3-diketones. 

The chirality of metal helicates can be demonstrated experimentally by X-ray crystal structure determinations and in solution by NMR spectroscopy. Addition of chiral shift reagents such as [Eu(tfc)3] (tfc = 3-(trifluoromethylhydroxymethylene)-(+)-camphorato) to selected helicates results in the splitting of some of the ligand signals as a consequence of the formation of diastereomeric complexes with the shift reagent. Such splitting is not observed for the free ligands, which are achiral. 

There are many hundreds of published reports on the use of achiral lanthanide tris(/3-diketonates) as NMR shift reagents. Essentially any substrate with an oxygen, nitrogen or sulfur atom is a potential candidate for analysis with lanthanide shift reagents. These include sulfur- and phosphorus-containing functional groups that have oxygen atoms. Carboxylic acids and phenols were observed to decompose lanthanide chelates of dpm, whereas solutions with chelates of fod were stable for several days and suitable for study. 

Achiral binuclear reagents have been added to mixtures of a chiral crown ether (74) and chloroform-soluble amino acid ester hydrochlorides to enhance the chiral discrimination in the NMR spectrum. The [Ln(fod)4] preferentially associated with the enantiomer in the bulk solution such that the enantiomer with lower association with 74 showed the larger lanthanide-induced shifts. The system also enhanced the chiral discrimination in acetonitrile-fifs, although [Pr(fod)4] was needed because it causes larger shifts than the... 

Enantiomeric distinction can also be achieved using chiral solvents without shift reagents. The determination of enantiomeric purity and the assignment of absolute configuration of cyclic and acyclic sulphinate esters has recently been achieved (573) using chiral l-aryl-2,2,2-trifluoroethanols as solvents. Enhanced enantiomeric distinction has been demonstrated using a combination of both a chiral solvent and an achiral LSR. (514)... 

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