Lanthanide shift reagents chiral

The enantiomeric purity of optically active sulphoxides can be determined by chiral lanthanide shift reagents such as tris(3-trifluoroacetyl-ti-camphorato)europium(III) and tris(heptafluorobutyryl-d-camphorato)europium(III)218-219-221, the latter shown in Scheme 23. 

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. 

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. 

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. 

There are three types of chiral auxiliary that are used chiral derivatizing agents (CDAs), chiral lanthanide shift reagents (CLSRs) and chiral solvating agents (CSAs)75. Chiral derivatizing agents (CDAs), such as the enantiomers of o -methoxy-o -(trifluoromethyl)phenylacetic acid (MTPA, 83)76, require the separate formation of discrete... 

The use of chiral lanthanide shift reagents (CLSRs) for NMR enantiomeric purity determination has become very popular (6) since the first of these compounds (54a) was reported by Whitesides and Lewis (96). Reagents 54b [Eu(hfbc)3 or Eu(hfc)3] and 54c [Eu(facam)3 or Eu(tfc)3] subsequently independently introduced by Fraser (97) and Goering (98), are most widely used, and are commercially available. 

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). 

Optically pure (3i )(—)-linalyl acetate was detected in the oils of clary sage Salvia sclarea). Salvia dominica, lavender and lavandin using H-NMR spectroscopy with a chiral lanthanide shift reagent, Eu(hfc)3. This enantiomer was also detected in the oils of lavender, lavandin and bergamot using complexation gas chromatography on Ni(hfc) 2, and... 

Separation of terpinen-4-ol enantiomers performed by a chiral GC columnand a chiral lanthanide shift reagent Eu(hfc)3, showed that the enantiomeric composition of an isolated compound from sweet marjoram oil was 73% (5)(- -) 27% R) —). The (4f )(—)-enantiomer was found in the oil of Eucalyptus dives Terpinen-4-ol was also found in several bark beetle species and is the main component in the aggregation pheromone of Polygraphuspoligraphus ... 

With Paramagnetic Chiral Lanthanide Shift Reagents... 

The determination of ee with chiral lanthanide shift reagents is normally performed in organic solvents. However, the development of chiral reagents capable of inducing shift nonequivalence in water, which is the appropriate solvent for many natural products, is of great importance. The europium(III) (R)-propylenediaminetetraacetate ion (Table 1) has been proposed as a chiral reagent suitable for use in aqueous solution90. 

The selection of a chiral lanthanide shift reagent capable of producing spectral nonequivalence in enantiomers is a matter of trial and error, as no reliable guidelines are available. Nevertheless. certain trends have emerged 74,sn95. 

However, there are two possibilities of deciding which of the two diastereomeric forms exists. Addition of a chiral auxiliary, e.g., a chiral lanthanide shift reagent, leads to a change in the spin-system type of the H signals. Examples of this kind of experiment are found in Section 4.1.1.4. 

A complete solution to the kinetic problem was attained through further studies of (2R, 3R)-1,2,3-d3-phenylcyclopropane and (1/ , 2S, 3 R) 1,2,3-d, -phenylcyclopropane-2-13C l6 Reaction mixtures from the first were analyzed by NMR and by Raman spectroscopy, and with the aid of the chiral lanthanide shift reagent Eu(hfc)3 on each derived mixture of deuterium-labeled benzoylcyclopropanes. Concentration versus reaction time data for all four isomers led to k22 = 0 and kx - 0.36 x 10 5 s. From kinetic work based on the l3C, d3-labelled substrate (equation 4) the final distinction between ka and k2 reactions was secured kl2 = 0.20 x 10 5s 1 andk2 0.87 x 10 5 s. Thanks to the 13C,d3 labeling, stereomutations allowed for equilibrations among eight rather than four isomers, and the distinction between k2 and kn products could be made163. 

The methyl groups of dimethyl sulfoxide are also anisochronous in the presence of chiral lanthanide shift reagents, such as Eu(facam) or Eu(hfbc)3 (Fig. 31)51). The enantiotopic carbinol protons of alcohols RCH2OH are similarly rendered anisochronous by chiral shift reagents 52 . 

Nuclear Magnetic Resonance Chiral Lanthanide Shift Reagents (Sullivan) 10 287... 

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