Kinetics and mechanism of the enantioselective passerini multicomponent reaction catalyzed by chiral ionic liquids

Abstract

Herein, we present the development of an enantioselective methodology for the classic Passerini threecomponent reaction, utilizing the asymmetric counteraniondirected catalysis (ACDC) effect combined with an ionic liquid catalyst to harness the ionic liquid effect. By combining both the ACDC and ionic liquid effects, the desired Passerini products were obtained in yields of up to 93% and with enantiomeric ratios of 94:6. To the best of our knowledge, this marks the first report of an asymmetric protocol for the classic Passerini reaction utilizing ACDC effects. DLS experiments provided insights into the catalyst’s effect through the formation of ionic aggregates and highlighted the importance of the solvent in achieving higher yields. NMR investigations revealed that the reaction mechanism proceeds through the formation of nitrilium and imidate species as key intermediates, followed by a Mumm rearrangement. Theoretical calculations confirmed S-isomer selectivity, with van der Waals forces stabilizing the transition state and the ionic liquid crucial to chiral catalysis. The first kinetics experiments conducted for this multicomponent reaction (MCR) provided additional support for these findings.