Direct Chiral ¹⁹F NMR Analysis of Fluorine-Containing Analytes and Its Application to Simultaneous Chiral Analysis

Abstract

We have demonstrated the efficient chiral analysis of fluorine-containing compounds by 19F NMR spectroscopy. The highly sensitive fluorine nucleus allowed chiral analysis of complex mixtures and even asymmetric reaction mixtures of multisubstrates. A single 19F NMR experiment was sufficient to determine the enantiomeric excesses and yields of the five products simultaneously.

A simple protocol for determination of enantiopurity of amines using BINOL derivatives as chiral solvating agentsvia1H- and19F-NMR spectroscopic analysis

“…The 13 Cand 19 F-NMR spectra were also recorded for secondary amines at 25 C. The 19 F-NMR spectroscopy is also benecial due to its 100% natural abundance and 83% signal sensitivity relative to 1 H-NMR spectroscopy and better separation of the signal due to less number of nuclei present in the analyte. 55 In this study, two examples of uorine containing analytes (10 and 11) are included. The analyte 10 (Dd R/S ¼ 0.14 ppm) shows more splitting of a signal as compared to analyte 11, which is having CF 3 group (Dd R/S ¼ 0.03 ppm) (see ESI, Fig.…”

Screening for Generality in Asymmetric Catalysis

“…For instance, the Anslyn and Wolf groups have developed circular-dichroism-based sensors that enable ee determination for compounds containing chelating functional groups (14,15). Other approaches have employed chiral 19 F-NMR shift reagents (16), fluorescent DNA biosensors (17), mass-tagging with pseudo-enantiomers (18), and selective enzymatic oxidation (19,20). Although these methods can provide high accuracy and sample throughput, more general analytical strategies are needed to conduct effective multi-substrate screening across a range of chemical space.…”

Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted 19F NMR Spectroscopy

“…The method described herein capitalizes on the presence of a fluorine atom in the studied molecule and can potentially be extended to study racemization kinetics of other fluorine-containing chiral molecules. While similar analytical chiral 19 F NMR methods have been described for various classes of compounds, − reported examples using 19 F NMR and CSAs to determine the rate of racemization are limited …”