Chiral-shift reagents and

If the amount of the sample is sufficient, then the carbon skeleton is best traced out from the two-dimensional INADEQUATE experiment. If the absolute configuration of particular C atoms is needed, the empirical applications of diastereotopism and chiral shift reagents are useful (Section 2.4). Anisotropic and ring current effects supply information about conformation and aromaticity (Section 2.5), and pH effects can indicate the site of protonation (problem 24). Temperature-dependent NMR spectra and C spin-lattice relaxation times (Section 2.6) provide insight into molecular dynamics (problems 13 and 14). 

Antipodal analysis by NMR employing eyelodextrins has several distinct advantages over derivatization and chiral shift reagent methods, namely ... 

Proton NMR and chiral shift reagent studies on various (/ )-l-alkoxy-2- 4-[4-(/ran5-4-pentylcyclohexy I)benzoyloxy]phenoxy) -propanes (83 and 84) failed to resolve the presence of any of the other enantiomer, indieating that the material was optically pure (ee >0.98, within experimental error) and that this system was now inherently stable to racemization. 

They were neutralised with quinine, nicotine, tartaric acid, mandelic acid or (+)-camphor-sulfonic acid. Naturally the optical rotation is changed by the salt formation, but it turns out that the optical rotation of a polymer salt (measured in DMF or methanol) does not depend only on the chemical structure, but also on the tacticity. For example, the optical rotation of the quinine salt of isotactic polystyrenesulfonic acid is considerably more negative than that of the atactic polymer. The tartrates of isotactic poly-2-vinylpyridine are more strongly dextrorotatory than the atactic ones. The optical rotation of the nicotine salts of isotactic and atactic polymethacrylic acid also differs greatly [83]. Finally, mention should be made of complex formation between polymers and chiral shift reagents. Since however the NMR signals and not the CD are investigated in such reactions, they are outside the scope of this report. 

Fig. 2.7. NMR spectrum of 1-phenyIethyIamine in the presence of a chiral shift reagent, showing differential chemical shift of methine and methyl signals and indicating ratio of R- to iS-enantio-mers. [Reproduced from J. Am. Chem. Soc. 93 5914 (1971) by permission of the American Chemical Society.]...

The submitters report obtaining the product in 99% yield. The enantiomeric excess of the Mosher ester of 3 was measured to be 98% using a Chiralcel OD column (40% 2-propanol/hexane). This optical purity measurement substantiated the optical purity assessment made by 111 NMR studies of 3 and racemic 3 prepared using a different method3. Addition of the chiral shift reagent tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium (III) resulted in clear resolution of the respective aromatic proton signals for the two enantiomers, which was demonstrated with the racemate. Under similar conditions, NMR analysis of 3 showed that within the detectable limits of the experiment (ca. <3%), there was none of the disfavored enantiomer. 

The enantiomeric excess (ee) of the hydrogenated products was determined either by polarimetry, GLC equipped with a chiral column or H-NMR with a chiral shift reagent. Methyl lactate and methyl 3-hydroxybutanoate, obtained from 1 and 2, respectively, were analized polarimetry using a Perkin-Elmer 243B instrument. The reference values of [a]o(neat) were +8.4° for (R)-methyl pyruvate and -22.95° for methyl 3-hydroxybutcinoate. Before GLC analysis, i-butyl 5-hydroxyhexanoate, methyl 5-hydroxyhexanoate, and n-butyl 5-hydroxyhexanoate, obtained from 1, 5, and 6, respectively, were converted to the pentanoyl esters, methyl 3-hydroxybutanoate was converted to the acetyl ester, and methyl 4-methyl-3-hydroxybutanoate obtained from 2 was converted the ester of (+)-a-methyl-a-(trifluoromethyl)phenyl acetic acid (MTPA). 

Sulfoxides without amino or carboxyl groups have also been resolved. Compound 3 was separated into enantiomers via salt formation between the phosphonic acid group and quinine . Separation of these diastereomeric salts was achieved by fractional crystallization from acetone. Upon passage through an acidic ion exchange column, each salt was converted to the free acid 3. Finally, the tetra-ammonium salt of each enantiomer of 3 was methylated with methyl iodide to give sulfoxide 4. The levorotatory enantiomer was shown to be completely optically pure by the use of chiral shift reagents and by comparison with a sample prepared by stereospecific synthesis (see Section II.B.l). The dextrorotatory enantiomer was found to be 70% optically pure. 

After removal of the solvent, the residue was eluted through a short silica gel column to remove the catalyst (elution with hexane ethyl acetate = 1 2). The eluent was concentrated in vacuo to give the product 2 (99 % yield) and the diastereoselectivity was determined by HPLC analysis (99 %). The enantios-electivity of the product was determined by lH NMR analysis with chiral shift reagent (+)-Eu(dppm) in CDCI3 and by chiral HPLC analysis (Chir-alcel-OD). 

Granot and Reuben report an example of an aqueous chiral shift reagent. In water, several proton resonances of norepinephrine exhibit nonequivalence in the presence of cobaltous adenosine-5 -triphosphate (101). 

Recently, new examples of asymmetric induction in the Pummerer reaction of chiral sulfoxides have been described. Oae and Numata (301) reported that the optically active a-cyanomethyl p-tolyl sulfoxide 275 undergoes a typical Pummerer rearrangement upon heating with excess of acetic anhydride at 120°C, to give the optically active a-acetoxy sulfide 276. The optical purity at the chiral a-carbon center in 276, determined by means of H- NMR spectroscopy using a chiral shift reagent, was 29.8%. 

Nuclear magnetic resonance ( H and C) chiral shift reagent chiral derivatizing agent chiral solvating agent. 

The limitations of NMR include the inability to directly distinquish enantiomers the addition of a chiral shift reagent or chiral solvating agent is necessary. Also, polymeric materials, where a large distribution of molecules are present, must be treated as a lumped parameter. At the moment, the biggest limitation of NMR seems to be that that the chemical shifts are perhaps too sensitive to local environment. Consequently, the signals are too non-stationary in position, and Eq. (2) becomes intractable in many, but not all, cases. 

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