Determination of Enantiomeric Excess in Confined Aprotic Solvent

The validation of the stereochemical purity of synthesized compounds is a requisite for the fine-chemical industry, particularly in the production of enantiopure drug compounds. However, most methodologies employed in the determination of enantiopurity require carefully chosen chiral GC or HPLC columns, increasing associated cost, analysis time, and complexity. Herein, we present a nanopore-based technology for the determination of enantiopurity, exploiting changes in ion-current rectification of quartz nanopipettes containing an aprotic organic electrolyte. Changes in solvent ordering at the quartz surface upon enantiomerically preferential adsorption give rise to distinguishable current-voltage responses. The applicability of our simple and cost-effective platform is demonstrated through the determination of the enantiomeric excess of commercially available (R)- and (S)-enantiomers of 4-methoxy-α-methylbenzylamine and duloxetine hydrochloride, as well as the product of a decarboxylative asymmetric allylic alkylation. Ion-current rectification (ICR)-based enantiomeric excess determination is completed within minutes, using negligible sample volumes and with simple low-cost electrical instrumentation.