The “cobra effect” in the imidazolinone series: how a donor can disable the nucleophilicity

Abstract

Electron-donating groups are known to enhance the nucleophilicity of a neighboring double bond or a cross-conjugated π-system through resonance or inductive effects. The illustrative example of this influence is the increased reactivity of enamines compared to enamides. Imidazolin-2-ones are a class of conformationally rigid cross-conjugated compounds that feature a cyclic enamide motif. Consequently, one would anticipate them to follow the same trend in nucleophilic reactivity. Herein, we demonstrate that this is not the case and the opposite behavior is observed. The nucleophilicity of the double bond in these compounds decreases upon the introduction of an electron-donating group. This unexpected effect is due to the stronger interaction of the substituent with a carbonyl group than with the double bond, so that the substituted imdazolin-2-one acts as a base rather than an enamide. We utilize this phenomenon for the synthesis of previously unknown 2-hydroxyimidazolium salts and demonstrate that the nucleophilic reactivity can be recovered by a careful choice of the solvent and catalyst.