The Assignment of the Absolute Configuration of β-Chiral Primary Alcohols with Axially Chiral Trifluoromethylbenzimidazolylbenzoic Acid

Abstract

Axially chiral trifluoromethylbenzimidazolylbenzoic acid (TBBA) was used as a chiral derivatization agent for the assignment of the absolute configuration of β-chiral primary alcohols. The structures varied from simple aliphatic alcohols to complex cyclic systems and highly substituted sugar derivatives. The NMR-based method was successfully implemented to evaluate 17 compounds and displayed ΔδPM values higher than 0.1 ppm in most cases, which makes TBBA superior to MTPA and MPA and comparable to 9-AMA.

Limitations of Trifluoromethylbenzoimidazolylbenzoic Acid as a Chiral Derivatizing Agent to Assign Absolute Configuration for β-Chiral Aminoalcohols

“…In summary, a small library of β-chiral N -Boc aminoalcohol TBBA esters was prepared. Their NMR spectra confirmed incongruity with the previously reported conformation model for β-chiral primary alcohols . Further expansion of the library with variously modified N -substituted phenylglycinols revealed similar nonconformity.…”

“…Their NMR spectra confirmed incongruity with the previously reported conformation model for β-chiral primary alcohols. 12 Further expansion of the library with variously modified N -substituted phenylglycinols revealed similar nonconformity. The increased acidity of the hydrogen atom in the carbamate or amide functionality has a strong influence on the formation of hydrogen bonds capable of changing the conformational equilibrium.…”

“…To explore whether anomalous Δδ PM values of ( S )-Boc-phenylglycinol 1 are an exception or trend from the previously proposed model ( Figure 1 ), 12 we prepared more structurally diverse TBBA esters of Boc-aminoalcohols ( Figure 2 ).…”

“…Recently, we reported a benzimidazole-based axially CDA, 2-(2-(trifluoromethyl)-1 H -benzo­[ d ]­imidazole-1-yl)­benzoic acid (TBBA), and its application toward α-chiral and β-chiral compounds . While the presented conformational model (Figure a–c) was reliable for various β-chiral analytes, the analysis of ( S )-Boc-phenylglycinol assigned the opposite configuration (Figure d).…”

Chiral Recognition of Hydantoin Derivatives Enabled by Tetraaza Macrocyclic Chiral Solvating Agents Using 1H NMR Spectroscopy

“…For this purpose, a variety of techniques and methods, such as high-performance liquid chromatography, X-ray crystallography, circular dichroism (CD), vibrational CD, nuclear magnetic resonance (NMR), UV–vis, and fluorescence spectroscopy, have been developed and utilized separately or in tandem. Among these available techniques, the 1 H NMR technique has several obvious advantages, associated with simple and fast measurement, accurate and convenient application, and employment of a low amount of samples, as well as the availability of a ubiquitous NMR apparatus in nearly all chemical laboratories . Thus, the NMR technique has widely emerged as the commonly applied tool for the determination of absolute configuration and quantitative analysis of ee of chiral substrates .…”