Europium compounds, chiral shift reagents

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 first report of the use of enantiomerically pure lanthanoid complexes as chiral Lewis acids for Diels-Alder-type reactions appeared in 1983.90 As shown in Figure 37, in the presence of (+)-Eu(hfc)3(tris(3-(heptafluoropropylhydroxy-methylene)-(+)-camphorato)europium(III)), usually utilized as a chiral shift reagent for NMR study, the hetero-Diels-Alder reaction of benzaldehyde (54) with compound 167 has been found to give 168 in 50% ee. 

Alkylation of 3-mercapto derivatives of 277-benzo-l-thia-2,4-diazine 1,1-dioxides (143 R = H, CH3, OCH3, Cl) with optically pure a- and /3-bromoesters (R = H, GH3 R = H, GH3) occurs exclusively at sulfur to provide 144 <1997TA2199> and 145 <1996TA2703>, respectively (Scheme 9). Both reactions occur mainly with Walden inversion and the ee of inverted products 144 was established by H NMR using the chiral shift reagent Eu(hfc)3 (Europium tris[3-(heptafluoropropylhydroxymethylene)-camphorate]) on the methyl esters of 144. These compounds also display the SIDA phenomenon (i.e., self-induced diastereomeric anisochronism), which results in the enantiomers having different chemical shifts for the ester CH3 and N-2 protons. 

Thermal cycloadditions of ketenimines to cait>onyl compounds requires activation of the 0=0 bond. The highly electrophilic bis(trifluoromethyl) ketone reacts at high temperature with diphenyl-N-to-lylketenimine (equation 73). Lanthanide shift reagents such as tris(6,6,7,7,8,8,8-heptafIuoro-2,2-di-methyl-3,S-octanedionato)-europium or -ytterbium [Eu(fod)3 or Yt(fod)a] are efficient catalysts for the cycloaddition of ketenimines with aldehydes (equation 74). The use of chiral catalysts such as tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato)-europium or -ytterbium [Eu(hfc)3 or Yt(hfc)3] has been found to generate only moderate enantiomeric excesses (20-40%). ... 

The second technique is to use a chiral lanthanide shift reagent (CLSR). Addition of certain lanthanide chelates, most commonly those of europium(III), to a solution of an organic compound in CDC13 or... 

A new n.m.r. shift reagent, tris-[3-(t-butylhydroxymethylene)-d-camphorato]-europium(m), should prove to be useful for the determination of enantiomeric purity of chiral / -phen ethyl amines.2 For example, it was found that the CHNH2 resonances of (R)- and (S)-amphetamines were separated by 0.7 p.p.m. in a carbon tetrachloride solution of the europium reagent ( 0.15 mol 1 l. In comparison to the use of optically active solvents for the same purpose, this technique has the advantage of showing very large shifts between resonances of enantiomers. Mass spectrometry has been used in the detection of mescaline and tetrahydro-isoquinoline precursors as biochemical intermediates.3 Spectral differences of 4-chloro-2-nitrobenzenesulphonyl derivatives of ephedrine and related compounds have been used for identification purposes.4... 

Which of the following compounds will form diastereomeric complexes with the chiral europium shift reagent 17 ... 

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