Impact of Backbone Substitution on Organocatalytic Activity of Sterically Encumbered NHC in Benzoin Condensation.

In this study, we provide a theoretical explanation for the experimentally observed decrease in the organocatalytic activity of N-aryl imidazolylidenes methylated at the C4/5-H positions in the benzoin condensation of aromatic aldehydes. A comparative quantum chemical study of energy profiles for the NHC-mediated benzoin condensation of furfural has revealed a high energy barrier to the formation of the IPrMe-based furanic Breslow intermediate that can be attributed to the negative steric interactions between the imidazole backbone methyl groups and N-aryl substituents.