Chiral shift reagents determination

The enantiomeric excess was determined by HNMR with ( + )-(/ )-binaphthol as a chiral shift reagent. The absolute configuration of the adducts was not determined. 

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). 

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). 

A 2 1 (- )-90-LAH reagent was employed in the asymmetric synthesis of a cij-diol (91) by reduction of c/j-2-acetoxy-6-phenylcyclohexanone (99,100). Diol 91 is of interest as the tetrahydro derivative of a metabolite obtained from the microbial oxidation of biphenyl. Diol 91 was obtained in 46% e.e. as determined by NMR in the presence of a chiral shift reagent. It was shown to have the absolute stereochemistry (lS,2/ )-dihydroxy-3(S)-phenylcyclohexane by oxidation to ( + )-2-(S)-phenyladipic acid of known absolute stereochemistry. 

Finally, one should note that the determination of enantiomeric purity by means of chiral shift reagents appears to be more advantageous than the method of Pirkle because the magnitude of nonequivalence A5 is generally greater, thus leading to a more accurate... 

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%. 

The use of chiral shift reagents, e.g. tris-[3-(trifluoromethyl)- or -(hepta-fluoropropyl)-hydroxymethylene)-d-camphorato)]europium, praseodymium, or ytterbium, in the determination of optical purities of chiral alcohols, ketones, esters, epoxides, amines, or sulphoxides, or in the separation of n.m.r. signals of internally enantiotopic protons e.g. PhCHjOH), has been described. 

The ee value of the enol acetate is determined indirectly by chemical correlation and is based on H-NMR spectroscopy of a derivative in the presence of a chiral shift reagent. 

Determined by two methods a) reduction with NaBH4 to the corresponding alcohol and acetylation, ee was then determined by 1H NMR using a chiral shift reagent, or b) the ephedrine method 29 using 13C-NMR spectroscopy on the derived oxazolidines. 

When the above-mentioned ring expansion with diazomethane 74) of trimethyl-dioxo[2.2]metacyclophane 65 (methylation was necessary to increase the inversion barrier to > 130 kJ) was performed in the presence of optically active alcohols at —60 °C, asymmetric induction occurred to an extent of ca. 40% ee (enantiomeric excess as determined by nmr-spectroscopy in the presence of chiral shift reagents)85). (+)-DibutyI tartrate favoured the dextrorotatory diketone 66 ([a]D 160° for the optically pure product) — the isomeric 67 was formed only with 3% ee (—)-ethyl lactate on the other hand led to an excess of (+)-67 ([a]D +240°) but gave (+)-66 with only 10% ee85). 

NMR shift differences between groups which are enantiotopic by external comparison (i.e. in enantiomers) may likewise be induced by either chiral solvents 26 27) or chiral shift reagents 52). Integration of the areas of signals of enantiomers so shifted is used for the determination of enantiomeric excess, a topic which cannot be taken up here but has been discussed elsewhere 53). 

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. 

By X-ray structural study of the complexes of 14b with (-)-34b and of 14c with (+)-34b, mechanism of the chiral recognition has been clarified.16 Optical purities of all enantiomers obtained by the resolution were determined by H NMR measurements in the presence of the new chiral shift reagent 3.17... 

Tanaka, K., Ootani, M., and Toda, F. (1992) Optically Active trans-Bis-(hydroxydiphenylmethyl)-2,2-dimethyl-l,3-dioxacyclopentane and Its Derivatives as Chiral Shift Reagents for the Determination of Enantiomeric Purity and Absolute Configuration, Tetrahedron Asymm., 3, 709-712. 

De-values were determined either 1H- or 13C-nmr-speetroscopically or by capillary gas chromatography. Ee-values were determined mainly by 1 H-nmr-spectroscopy using chiral shift reagents. >95% de or ee was assumed, if only one stereoisomer was detectable in the spectrum. 

On hydrolysis of 32 (2 equivalents 0.25 N HC1, r.t.) L-Val-OCH3 and the (R)-amino acid methyl esters 34 are liberated. Their ee can be determined H-nmr-spectroscopically using chiral shift reagents (Table 4)16). 

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