It is known that depending on the nature of catalyst-substrate interactions, N-heterocyclic carbene (NHC)-mediated organocatalytic reactions proceed by two principal pathways that involve either covalent bonding or non-covalent interactions. A classical well-established pathway involves Breslow intermediates and is applicable for highly electrophilic or non-enolizable substrates (such as aldehydes, ketenes, acyl fluorides or aryl esters). Another pathway is characteristic to uncommon organocatalytic reactions of an NHC with enolizable and less nucleophilic ketones, diketones or esters where the carbene acts as a strong base.
In this work, conducted by the researchers of the Zelinsky Institute, it was discovered that organocatalysis proceeding via a covalent interaction of imidazolium carbenes with carbonyl substrates had a dynamic nature. Imidazolium cations show ambident nucleophilicity towards carbonyl compounds centers depending on the steric properties of the substrates and reaction conditions. This fact can be explained by the formation of the H-bonded abnormal carbene (aNHC) and ditopic carbanionic carbene (dcNHC) during the process. The discovered phenomenon provides further opportunities for the development of a new type of NHC-based organocatalysis proceeding via a carbene/enolizable ketone covalent interaction.
K. I. Galkin, B. Ya. Karlinskii, A. Yu. Kostyukovich, E. G. Gordeev, V. P. Ananikov Ambident Reactivity of Imidazolium Cations as Evidence of the Dynamic Nature of N-Heterocyclic Carbene-Mediated Organocatalysis Chem. Eur. J., 2020, 26, 8567-8571, DOI: 10.1002/chem.201905704