Cross-Cycloaddition of Two Different Isocyanides to Imidazoles

Significance

An efficient Cu-catalyzed cross-cycloaddition between arylisocyanides 1 and ethoxycarbonylmethyl isocyanide 2 to afford imidazoles is reported. Among the different ligands tested, 1,10-phenanthroline/Cu₂O was shown to give the best results. Arylisocyanides bearing electron-donating, -withdrawing, and sterically hindered groups were shown to perform well in the reaction. However, aliphatic isocyanides led to homo-cycloaddition products of 2. As a possible mechanism, the Cu₂O-mediated C-H-bond activation of 2 followed by nucleophilic addition to 1 to generate the α-cuprioisocyanide A is proposed. Intramolecular attack of imine nitrogen to the isocyanate carbon, followed by 1,3-proton transfer, leads to the 4-cuprioimidazole intermediate B which, upon Cu exchange, leads to the final product.