Chiral solvating agents enantiomeric purity

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. 

Consequently, the splitting observed is due to the fact that TRIMEB induces nonequivalence in the proton nuclei of the two enantiomers of the allenes, thus enabling one to determine the enantiomeric purities by using a chiral solvating agent. In all cases examined the extent of the nonequivalence, i.e. the difference of the proton chemical shifts of the two enantiomers in the presence of TRIMEB, can be increased by increasing the... 

NMR spectroscopy the NMR spectrum of the sample in the presence of a chiral solvating agent (see Section 3.1.4.1.) or a chiral paramagnetic lanthanide shift reagent (see Section 3.1.4.2.2.) is recorded. The determination of enantiomeric purity rests on the nonequivalence of externally enantiotopic nuclei which are rendered externally diastereotopic in a non-racemic chiral environment. 

In 1965, the determination of the enantiomeric purity (ee) by NMR spectroscopy using a chiral solvating agent (CSA)69- 73 was first postulated17 and demonstrated experimentally by Pirkle in 1967. An example is the nonequivalence of the proton and fluorine resonances of racemic 2,2,2-trifluoro-l-phenylethanol in the presence of optically active 1-phenylethanamine78 or l-(l-naphthyl)ethanamineS3 (Figure 5). 

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). ... 

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. ... 

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. 

The enantiomeric purities of compounds related to (31), where the chlorine atom has been replaced by an alkylamino group, have been determined by P NMR studies using chiral solvating agents <87JOC5320>. 

GC studies) bislactim ethers 2R,5R)-4a, (25,5/ )-4a, (2/f,5/f)-4b, and (2S,5R)-4h were subsequently hydrolyzed with hydrochloric acid at 0°C to jdeld the respective P-(trimethylsilyl)alanine esters (R)-5a and S)-5a and the P-(trimethylgermyl)alanine esters (7 )-5b and (S)-5b. As shown by H-NMR studies using the chiral solvating agent (R>(-)-l-(9-anthryl)-2,2,2-trifluoroethanol, the enantiomeric purities of these esters were >98 % ee. Hydrolysis of the esters (R)-5a, (S)-5a, (R)-5b, and (S -5b in boiling hydrochloric acid and subsequent treatment of the resulting a-amino acid hydrochlorides with propylene oxide yielded the title compounds (R)-la, (S)-la, (R)-lb, and f5)-lb as colorless crystalline solids. 

Enantiomerically pure lactonic pheromones 607-611, of the carpenter bee, blacktailed deer, Japanese beetle, rove beetle, and Oriental hornet, respectively, have been synthesized from racemic cyano alcohols of type 612. The key to the success of the overall approach is the facile separation of diastereomeric carbamates derived from cyano alcohols of type 612 by automated multigram LC. The chosen approach also facilitates the assignment of absolute configurations to the lactone enantiomers and their precursors. In the case of 607, direct determination of enantiomeric purity and absolute configuration is also possible using the chiral solvating agent 2,2,2-trifluoro-l-(9-anthryl)ethanol [439]. 

A few commercial carboxylic acids (e.g. (5)-Naproxen) that are chiral solvating agents could be used as reagents in the determination of enantiomeric purity of phosphine oxides. ... 

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. 

When a chiral solute dissolves in a chiral solvent then a stereochemical interaction must be involved. The expense of using a chiral material as a bulk solvent for NMR determination of enantiomeric purity is rarely justified. A solvating agent is added in between 1 to 10 mole equivalents to a solution of the solute enantiomers in an achiral bulk... 

Wenzel TJ, Bourne CB, Clark RL. (18-Crown-6)-2,3,ll,12-tetracarhoxylic acid as a chiral NMR solvating agent for determining the enantiomeric purity and absolute configuration of (3-amino acids. Tetrahedron Asymm. 2009 20 2052-2060. 

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