The resolution of enantiomers remains one of the most difficult tasks for organic chemists. Determination of enantiomeric excess is generally done by either HPLC or chiro-optical methods, such as optical rotation. These techniques suffer from disadvantages inherent to the methods themselves. HPLC methods are highly analyte, method, and instrument dependent and results are often not repeatable. Determination of the enantiomeric excess by optical rotation requires that first the value for a single isomer be obtained, which is difficult if nigh impossible. Because of these challenges, the NMR based method of chiral solvating agents (CSA) have been growing in popularity. Chiral solvating agents function by using non-covalent interactions with the analyte to form diastereomeric complexes in solution, which leads to different NMR spectra. While numerous cores of CSAs have been previously reported, the amide functional group remains one of the most prevalent. From this core, the idea of a thioamide-based CSA was developed, as it has never been reported as a core for CSA. To this end, the thioamide variant of the well-known Kagan’s amide CSA (3,5-dinitro-<i>N</i>-[(1R)-1-phenylethyl]benzamide) has been synthesized through a 2-step process. This material has shown improved resolution up to 0.55 ppm from the amide for a multitude of amides and mandelic acid derivatives, along with displaying improved solubility factors.

Increased chemical shift resolution of enantiomers with a thioamide-based chiral solvating agent

ACS Spring Meeting 2021

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