Using an Automated Monitoring Platform for Investigations of Biphasic Reactions

Insights and mechanistic studies into biphasic reactions are often challenging due to difficulty in deploying in situ reaction-monitoring or sampling procedures. Herein, we describe the development and application of an automated monitoring platform capable of delineating time course reaction progress of biphasic reactions. The system was applied toward a case study of an enantioselective biphasic spirocyclization catalyzed by a doubly quaternized cinchona alkaloid. A combination of heterogeneous and phase-selective sampling, coupled with high-performance liquid chromatography mass spectrometry (HPLC MS), allowed for the detection, quantification, and identification of reactive species in either the heterogeneous liquid liquid mixture or isolated organic phase throughout the reaction. The data gathered using this method allowed for valuable insight into catalyst phase-transfer behavior, elucidation of catalyst decomposition pathways, and the determination of rate laws governing the reaction. This method is adaptable and will provide a robust means for the investigation of biphasic reactions.