Chiral Recognition Studies of α-(Nonafluoro-tert-butoxy)carboxylic Acids by NMR Spectroscopy

Abstract

Three chiral α-(nonafluoro-tert-butoxy)carboxylic acids (R)-1, (RS)-2, (R)-3 were synthesized to examine their application as chiral solvating agents with amines. As a model compound, first (S)- and/or (RS)-α-phenylethylamine was used, and their diastereomeric salts were investigated by (1)H and (19)F NMR and ECD spectroscopy. The NMR spectroscopic studies were carried out at room temperature using the slightly polar CDCl3 and apolar C6D6 as solvents in 5 mM and 54 mM concentrations. The difference of the chemical shifts (Δδ) in the diastereomeric complexes is comparable with other, well-known chiral derivatizing and solvating agents (e.g., Mosher's acid, Pirkle's alcohol). Diastereomeric salts of racemic acids (RS)-1 and (RS)-2 with biologically active amines (1R,2S)-ephedrine and (S)-dapoxetine were also investigated by (19)F NMR spectroscopy.

Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds

“…A wide variety of fluorine-containing reagents have been developed for NMR chiral discrimination [ 26 , 27 ]. In 2015, Nemes et al described the chiral recognition studies of α-(nonafluoro- tert -butoxy)carboxylic acid by 19 F-NMR spectroscopy [ 28 ]. Carboxylic acids 1 and 2 were synthesized to be enantiomerically enriched in order to obtain a CDA ( Scheme 1 ).…”

(+)-BINOL and Pure Shift Experiment: A Bidirectional Approach for NMR Chiral Discrimination of Overcrowded Spectra of Primary Amines

“…The results evidently validated its utility for discrimination on arylalkylamines, as signal separation obtained by NMR chiral discrimination using only the (+)-BINOL 1b was comparable with other protocols which require more complex procedures. [40][41][42][43][44][45] When evaluating these results, the greater separation of arylalkylamines 2a, 2b, 2c and 2f compounds occurred due to steric hindrance and chemical shift anisotropy caused by the aromatic ring. The influence of the aromatic ring in the substrates evaluated is supported by the smaller split signals using the alkylamines 2d, 2e, 2g, 2h and 2j.…”

Recent advances of the ionic chiral selectors for chiral resolution by chromatography, spectroscopy and electrochemistry

“…In NMR, choosing an appropriate chiral solvating agent (CSAs) or enantiopure chiral derivatizing agent is important to form noncovalent interactions with the testing samples for chiral recognition. It can generate the diastereomeric complexes with enough chemical shift [109][110][111][112]. Different from chromatography, fluorescence spectroscopy, and electrochemical analysis, it has none specific conditions to the isomers, like, stability, ultraviolet absorption, or others.…”