Selected Ion Monitoring Using Low-Cost Mass Spectrum Detectors Provides a Rapid, General, and Accurate Method for Enantiomeric Excess Determination in High-Throughput Experimentation

High-throughput experimentation (HTE) workflows are efficient means of surveying a broad array of chiral catalysts in the development of catalytic asymmetric reactions. However, the use of traditional high-pressure liquid chromatography (HPLC)-UV/vis methodology to determine enantiomeric excess (ee) from the resulting reactions is often hampered by coelution of other reaction components, resulting in erroneous ee determination when crude samples are used and ultimately requiring product isolation prior to ee analysis. In this study, using four published reactions selected as model systems, we demonstrate that the use of liquid chromatography–mass spectrometry (LC–MS), supercritical fluid chromatography–mass spectrometry (SFC-MS), and selected ion monitoring (SIM) mass chromatography provides a highly accurate means to determine the ee of products in crude reaction samples using commonplace, low-cost MS detectors. Using ion selection, coeluting signals can be deconvoluted to provide accurate integrations of the target analytes. We also show that this method is effective for samples lacking UV/vis chromophores, making it ideal for HTE workflows in asymmetric catalysis.