Chiral solvating agents for NMR

In conclusion, the most important result is that the use of permethylated cyclodextrin as chiral solvating agent for NMR spectroscopy not only affords a simple and practical way for the determination of the stereochemical purities of trisubstituted allenes, but also allows one to simultaneously determine their absolute configuration. Indeed, TRIMEB induced only positive complexation shifts of all the allene protons, which are greater for the (S )-enantiomer than for the (R)-enantiomer, independent of the structure of the allene. This empirical correlation seems to be reliable since it has been satisfied by a large number of trisubstituted allenes. 

Chiral Solvating Agent NEA is an effective chiral solvating agent for NMR determination of enantiomeric purity. The combination of enantiomerically pure NEA (3-5 mol excess) and racemic solute causes the NMR spectra of the diastereomerically solvated enantiomers to differ. Since NEA is an efficient hydrogen-bond acceptor, it solvates better if the solute is a hydrogen-bond donor. (R)-(+)-NEA has been used to determine the enantiomeric purity of a variety of substrates. ... 

Pirkle WH, Tsipouras A. 3, 5-Dinitrobenzoyl amino acid esters. Broadly applicable chiral solvating agents for NMR determination of enantiomeric purity. Tetrahedron Lett. 1985 26 2989-2992. 

Koscho ME, Pirkle WH. Investigation of a broadly applicable chiral selector used in enantioselective chromatography (Whelk-O 1) as a chiral solvating agent for NMR determination of enantiomeric composition. Tetrahedron Asymm. 2005 16 3345-3351. 

Strict analytical applications of induced CD have been limited, and the methodology has primarily been used to study the modes of interaction between the solute and the chiral environmental substance. Nevertheless, this information can be extremely valuable in support of alternate analytical methodology. For example, the enantiomeric composition of a compound can be measured using chiral solvating agents and NMR spectroscopy. It is not difficult to see how the mechanism of interaction could be probed in additional detail through the CD induced in the solute absorption bands. 

V,5S)-5-Amino-4-phenyl-2,2-dimethyl-l,3-dioxane and (4i ,5i )-5-amino-(4 -biphenyl)-2,2-dimethyl-1,3-dioxane were synthesized and employed as chiral solvating agents for the ee determination of compounds bearing an acidic proton by means of NMR spectroscopy (99TA323). Based on the rigid conformation of the two amines, they are... 

In addition, OPEN is an efficient chiral solvating agent for determination of the enantiomeric excess in the H NMR analysis of various chiral mono- and dicarboxylic acids including a-arylpropanoic and a-halo carboxylic acids. The chemical-shift non-equivalence (S A) in certain diastereomeric complexes is greater than 0.05 ppm. A DPEN/Pd(II) complex can be used for determination of enantiomeric excess of the non-protected chiral amino acids by H and C NMR analysis. For example, Pd[(S,S)-dpen](D20)2 and racemic alanine with a base forms the square-planar complex (eq 14). The 5 A of H-NMR resonance in the diastereomeric complexes in D2O is 0.056 ppm, while this complex hardly dissolves in D2O. 

Because snsnXioseparation proved to be impossible for DIBOA and DIMBOA attempts to accomplish at least an cnantiodifferentiation by means of the chiral solvating agent (CSA) NMR technique have been undertaken because NMR is based upon a rapid measuring and differentiation process in comparison to the chromatographic separation processes. The NMR discrimination of enantiomeric cyclic hemiacetals and methyl acetals was not described yet. On principle, a pair of... 

Rudzinska E, Berlicki L, Kafarski P, Lammerhofer M, Mucha A. Cinchona alkaloids as privileged chiral solvating agents for the enantiodiscrimination of A-protected aminoalkanephosph-onates - a comparative NMR study. Tetrahedron Asymm. 2009 20 2709-2714. 

Many cyclodextrin derivatives have been evaluated as chiral NMR solvating agents. Permethylated a- and (3-cyclodextrins are commercially available and can be used in water or organic solvents. Of particular note is the use of permethylated a- and 3-cyclodextrin as a chiral solvating agent for trisubstituted allenes 69. ... 

UcceUo-Barretta G, Balzano F, Caporusso AM, lodice A, Salvadori P. Permethylated p-cyclodextrin as chiral solvating agent for the NMR assignment of the absolute configuration of chiral trisubstituted allenes. J. Org. Chem. 1995 60 2227-2231. 

Nuclear Magnetic Resonance Spectroscopy Measured in a Chiral Solvent or with a Chiral Solvating Agent. One method of NMR analysis for enantiomer composition is to record the spectra in a chiral environment, such as a chiral solvent or a chiral solvating agent. This method is based on the diastereomeric interaction between the substrate and the chiral environment applied in the analysis. 

Barretta and coworkers63 reported a direct determination of the enantiomeric purity of chiral trisubstituted allenes by using permethylated cyclodextrin as a chiral solvating agent. They found that the heptakis ft-cyclodextrin TRIMEB discussed above can be successfully used as a chiral solvating agent (CSA) for the NMR determination of the enantiomeric purity of trisubstituted allenes llOa-f. An accurate analysis of the experimental conditions (molar ratio aliene/TRIMEB, temperature and solvent) required to optimize the enantioseparation has been carried out. The XH NMR spectra of TRIMEB, allenes llOa-f, and the mixtures TRIMEB/allene have been recorded at 300 MHz in CD3OD as solvent. 

For reviews of nmr chiral solvating agents, see Weisman, in Morrison, Ref. 88, vol. I. pp. 153-171 Pirkle Hoover Top. Stereochem. 1982,13, 263-331. For literature references, see Sweeting Anet Org. Magn. Resort. 1984, 22, 539. Sec also Pirkle Tsipouras Tetrahedron Lett. 1985, 26, 2989 Parker Taylor Tetrahedron 1987, 43, 5451. 

Noncovalent MTPA Derivatives. The enantiomeric purity of some chiral amines can be determined by H NMR with (S)- or (J )-MTPA as a chiral solvating agent. The method is particularly useful for chiral tertiary amines that are not amenable to conversion into MTPA amides, e.g. (18) and (19), although it has been utilized for primary and secondary amines as well, e.g. (20). ... 

CSA (Chiral solvating agent) A diamagnetic additive of known enantiomeric purity used to induce anisochrony in enantiomers of a racemate for NMR analysis. See Section 2.3.4. 

For the analysis of compounds that are chiral by virtue of isotopic substitution, NMR is the method of choice, since energetic differences between diastereomeric complexes are not required for induced anisochrony. When it works, NMR is also one of the simplest and fastest techniques available. For monofunctional or weakly basic solutes, chiral shift reagents are more likely to succeed, whereas chiral solvating agents are simpler (when they work) and are better for the assignment of absolute configuration. 

Chiral solvation agents, chiral solvents and chiral liquid crystals. The differentiation of two enantiomers by NMR is possible by studying them in the presence of a chiral solvent or in chiral liquid crystals. The molecule-solvent or molecule-liquid crystal interaction is sufhciently energetic for the diastereomeric association to have a lifetime longer than the NMR timescale. 

---