Ambident Reactivity of Imidazolium Cations as Evidence of the Dynamic Nature of N‐Heterocyclic Carbene‐Mediated Organocatalysis

Abstract

This work reveals ambident nucleophilic reactivity of imidazolium cations towards carbonyl compounds at the C2 or C4 carbene centers depending on the steric properties of the substrates and reaction conditions. Such an adaptive

Organocatalytic Deuteration Induced by the Dynamic Covalent Interaction of Imidazolium Cations with Ketones

“…According to the mechanistic investigations carried out in the present work and previous study of dynamic reactivity of imidazolium cations towards ketones, [12] a general pathway may be proposed for the deuteration reaction as shown on Scheme 4 (see also Figure S3 for a more details). Relative intensities of the peaks in ESI‐MS spectra corresponding to the imidazolium cation/acetone adducts in the reaction mixtures were in accordance with the catalytic activity of corresponding imidazolium salts in the deuteration process: only imidazolium salts [ 1 a ]Cl and [ 1 k ]Cl containing α‐unbranched N ‐alkyl substituents (which showed the highest amounts of the imidazolium cation/acetone adducts in the ESI‐MS and NMR spectra) has the best catalytic activity in the deuteration process (compare Table 1 and Table S1).…”

“…[11c] In our previous work, we described the ambident reactivity of imidazolium cations towards aldehydes and ketones leading to the formation of a mixture of the C2 and C4 adducts as kinetic and thermodynamic products, respectively (Scheme 2A). [12] This phenomenon, explained by in situ generation of the H-bonded abnormal NHCs (aNHCs) and the ditopic carbanionic NHCs (dcNHCs) along with the classical C2 carbenes from the cationic imidazolium precursors, reflects the dynamic nature of organocatalysis mediated by a covalent interaction of NHCs with carbonyl substrates. In the case of ketones, the formation of the C4 adducts by aNHC-and dcNHC-based mechanisms was found possible, and the preference for the dcNHC pathway was theoretically explained.…”

Catalyst-controlled stereoselective carbon–heteroatom bond formations by N-heterocyclic carbene (NHC) organocatalysis

“…The development of new NHC catalyst structures is highly desirable to improve their stabilities and reactivities, which could ensure smooth transformations by lowering the catalyst loadings (ideally less than 0.1 mol%) with high efficiency and a broad substrate scope and may inspire applications of the NHC-catalyzed enantioselective preparation of functional molecules in industrial chemical processes. Additionally, although detailed mechanistic cycles have been proposed for most examples, some recent studies by Ananikov 139,140 and Hollóczki 141 reveal interesting observations distinct to the classical carbene catalytic process. It is essential to thoroughly examine the detailed mechanism of the catalytic C–X bond construction reactions, particularly the versatile role of reactive “carbene” species.…”

Proton–deuterium exchange of acetone catalyzed in imidazolium-based ionic liquid–D2O mixtures

“…29,30 Recently, a dynamic nature of imidazolium systems was revealed and ambident reactivity with carbonyl compounds was shown in organocatalytic processes. 31 Reactions involving ketones are of particular interest with challenging questions from the mechanistic point of view. 31 Acetone, despite being a small molecule, was established as a reliable model for studying the deuteration reactions of ketones and gain mechanistic understanding.…”

“…31 Reactions involving ketones are of particular interest with challenging questions from the mechanistic point of view. 31 Acetone, despite being a small molecule, was established as a reliable model for studying the deuteration reactions of ketones and gain mechanistic understanding.…”