Combined Role of the Asymmetric Counteranion-Directed Catalysis (ACDC) and Ionic Liquid Effect for the Enantioselective Biginelli Multicomponent Reaction

Abstract

This work describes new chiral task-specific ionic liquids bearing chiral anions as the catalysts for the enantioselective multicomponent Biginelli reaction. For the first time, the combined role of asymmetric counteranion-directed catalysis (ACDC) and ionic liquid effect (ILE) for the chiral induction in the Biginelli multicomponent reaction is demonstrated. The chiral induction arises from a supramolecular aggregate where the anion and the cation of the catalyst are alongside with a key cationic intermediate of the reaction. Each component of the new catalyst had a vital role for the chiral induction success. The mechanism of an asymmetric version of this multicomponent reaction is in addition demonstrated for the first time using electrospray (tandem) mass spectrometry, ESI-MS(/MS). The analyses indicated the reaction takes place preferentially and exclusively through the iminium mechanism. Unprecedented supramolecular aggregates were detected by ESI-MS and characterized by ESI-MS/MS. No intermediate of the other two possible reactions pathways could be detected. Theoretical calculations shed light on the transition state of the transformation during the key step of the chiral induction and helped to elucidate the roles of the chiral anion (ACDC contribution) and of the imidazolium-containing nonchiral cation derivative (ILE contribution) in the molecular reaction process.

Immobilized Gold Nanoparticles Prepared from Gold(III)-Containing Ionic Liquids on Silica: Application to the Sustainable Synthesis of Propargylamines

“…In the third cycle, the chloride catalyst hardly showed any activity, whereas the hexafluorophosphate catalysts showed only a very small decrease in the benzaldehyde conversion ( Table 4 ). The dependence of the physicochemical properties and activity of the imidazolium ILs on the anion is not surprising and has been widely reported in the literature [ 90 , 91 ].…”

How and Why to Investigate Multicomponent Reactions Mechanisms? A Critical Review

“…[81][82][83] Although it is indeed the preferred reaction pathway typically observed for this MCR, the actual mechanism of the enantioselective version has remained unexplored but was recently investigated by our group. [84] To favor the iminium mechanism and the chiral induction step, in most studies the iminium ion is preformed prior to the 1,3-dicarbonyl addition. The 1,3dicarbonyl reagent then undergoes an enantioselective controlled addition to the preformed intermediate.…”

“…Enantioselective Biginelli reactions are alleged to proceed through the iminium‐like mechanism [81–83] . Although it is indeed the preferred reaction pathway typically observed for this MCR, the actual mechanism of the enantioselective version has remained unexplored but was recently investigated by our group [84] . To favor the iminium mechanism and the chiral induction step, in most studies the iminium ion is preformed prior to the 1,3‐dicarbonyl addition.…”

Heterobifunctional Rotaxanes for Asymmetric Catalysis

“…To our knowledge,t he phosphate-ammonium-catalyzed Michael addition has not yet been investigated theoretically. [16] We set out to explore the structures of rate-and stereodetermining intermediates and to rationalize the experimentally observed trends in reaction rates and stereoselectivities based on high-level density function theory (DFT) calculations.O ur well established state-of-the-art DFT protocol (at the PW6B95-D3/def2-QZVP + COSMO-RS// TPSS-D3/ def2-TZVP + COSMO level [17] in THF solution) was applied, and the final Gibbs free energies (at 298 Kand 1m reference concentration) are used in our discussion. Thei nitial structures and reaction paths were explored with the efficient GFN-xTB method.…”