Chiral Ionic Liquid/ESI‐MS Methodology as an Efficient Tool for the Study of Transformations of Supported Organocatalysts: Deactivation Pathways of Jørgensen–Hayashi‐Type Catalysts in Asymmetric Michael Reactions

Abstract

The deactivation pathways of Jørgensen-Hayashi-type organocatalysts modified with an ionic liquid fragment in asymmetric Michael reactions of α,β-enals with C- (nitromethane, dimethylmalonate) or N-nucleophiles (N-carbobenzyloxyhydroxylamine) that involved an iminium-ion formation step were studied for the first time by the electrospray ionization mass spectrometry (ESI-MS). "Parasitic" side reactions and undesirable cation intermediates that poisoned the catalysts were identified in accordance with their m/z values as well as their relation to the reported mechanisms of Michael reactions in the presence of O-TMS-α,α-diarylprolinol (TMS=trimethylsilyl) derivatives. The proposed approach may be useful for the study of transformations of other types of organocatalysts modified with ionic groups in various organocatalytic reactions and for the development of novel robust catalysts and processes that would be suitable for large-scale industrial applications.

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

“…More importantly, however, additional species that are not present in the unlabeled reference system have not been observed. There are no indications for an interference of the charge tag with the catalysis, in contrast to the findings with the flexible imidazolium-labeled proline derivatives reported previously [43]. …”

“…Few proline derivatives carrying a covalently fixed charge have been reported by now [43,53]. They consist of an imidazolium salt attached to hydroxyproline via an ester group at the end of a flexible alkyl spacer.…”

“…They consist of an imidazolium salt attached to hydroxyproline via an ester group at the end of a flexible alkyl spacer. Interestingly, such charge tags can cause an enhancement of the catalytic performance through electrosteric activation [53], but backfolding can also alter and disturb the catalytic process and induce the formation of side products [43]. In order to fix the charge far away from the catalytic center and thus leave the original catalytic activity of L-proline preferably undisturbed, we chose a stiff 1-ethylpyridinium unit as charge-carrier separated from the catalytic center by a rigid phenyl linker (Fig.…”

Integration of aerobic oxidation and intramolecular asymmetric aza-Friedel–Crafts reactions with a chiral bifunctional heterogeneous catalyst

“…3 c While we were able to demonstrate that our fabrication method prevented catalyst deactivation between the Au/Pd NPs and the chiral organocatalyst to enable the asymmetric TOP, it was discovered that the chiral secondary amine catalyst was deactivated under aerobic conditions and that the heterogeneous catalyst could not be reused. Based on our preliminary experimental studies and related literature, 8 we concluded that the use of chiral heterogeneous secondary amines as organocatalysts for asymmetric TOPs was not a viable strategy due to the propensity of the covalent intermediates to undergo aerobic oxidation and become degraded. Therefore, we hypothesized that the use of chiral organocatalysts which activate the organic substrates through non-covalent interactions would lead to a more robust heterogeneous system that could be recovered and reused even under aerobic conditions.…”

1,2,3-Triazolium Salts as a Versatile New Class of Ionic Liquids

“…While this phenomenon does not give a great effect in a single organocatalyzed reaction, it becomes crucial when the organocatalyst is repeatedly used after recycling. As shown by the same group oxidative poisoning of the ionic liquid tagged organocatalysts could be circumvented by working under oxygen free conditions (Maltsev, Chizhov et al 2011). It seems to be worthy to examine the applications of 1,2,3-triazolium-based ionic liquid tagged organocatalysts in organocatalyzed reaction running via intermediate enamines under oxygen free conditions because a better performance can be expected after recycling.…”