A chiral phosphazane reagent strategy for the determination of enantiomeric excess of amines

Abstract

The simple inorganic cyclodiphosph(iii)azane chiral derivatisation agent ClP(μ-tBuN)2POBorn (Born = endo-(1S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl) is shown to be effective in the measurement of ee’s of chiral amines using 31P NMR spectroscopy.

Oligopeptide (FK)4facilitates the determination of the absolute stereochemistry of chiral organic compoundsviaNMR Spectroscopy

“…However, distinguishing between mirror-imaged enantiomers remains challenging due to the complexity of theoretical calculations predicting the miniscule change in stereoisomeric conformations and respected chemical shifts of the analyte molecules while taking into account the alignment medium 18,19 . On the other hand, converting enantiomers to diastereomers using a chiral auxiliary such as a chiral derivatization agent (CDA) [20][21][22] or chiral solvating agent (CSA) 8,[22][23][24][25] facilitates successful chiral recognition. This feature of the chiral differentiating agent could potentially enhance the elucidation of absolute configuration when combined with the characteristic of alignment media.…”

“…This feature of the chiral differentiating agent could potentially enhance the elucidation of absolute configuration when combined with the characteristic of alignment media. Current chiral auxiliaries mainly consist of small molecules that freely diffuse in the solution environment 8,[20][21][22][23][24][25] , while reported alignment media usually demonstrate equivalent interactions with a pair of enantiomers 26,27 . The lack of suitable agents limits current applications in conjunction.…”

19F NMR enantiodiscrimination and diastereomeric purity determination of amino acids, dipeptides, and amines

“…Chiral amino-group compounds are not only important biomolecules but also chemical and pharmaceutical intermediates for the synthesis of bioactive compounds. Currently, various methods have been widely used for the elucidation of absolute configuration and enantiomeric excess (ee), including NMR, [1][2][3][4][5][6][7][8][9][10][11][12] circular dichroism, [13][14][15][16][17] fluorescence, 18 SERS, 19 chromatography, 20,21 ion mobility mass spectrometry, 22 and electrochemistry. 23,24 However, optical spectroscopic techniques require pure enantiomers that are obtained by isolating each enantiomeric pair or by extracting each enantiomer from its original matrix prior to analysis.…”

“…23,24 However, optical spectroscopic techniques require pure enantiomers that are obtained by isolating each enantiomeric pair or by extracting each enantiomer from its original matrix prior to analysis. For NMR methods, 1 H and 19 F NMR are commonly utilized in enantiospecific analysis relying on the discriminative resonance signals of the diastereoisomers generated by CSA or CDA. Despite their high sensitivity, the use of NMR active 1 H nuclei in complex samples has been limited due to a narrow chemical shift range (∼14 ppm) and the potential for signal overlap.…”

“…For NMR methods, 1 H and 19 F NMR are commonly utilized in enantiospecific analysis relying on the discriminative resonance signals of the diastereoisomers generated by CSA or CDA. Despite their high sensitivity, the use of NMR active 1 H nuclei in complex samples has been limited due to a narrow chemical shift range (∼14 ppm) and the potential for signal overlap. 19 F has an excellent NMR sensitivity (83.4% relative to 1 H), and occurs naturally in 100% abundance.…”