C(2)-Functionalization of 1-substituted imidazoles with cyanoacetylenes and aromatic or heteroaromatic aldehydes

Substituted imidazoles (substituents are Me, Et, i-Bu, n-Hexyl, (CH2)2S–Bu-n, Ph, Bn) react smoothly (room temperature, without catalyst and solvent) with cyanoacetylenes (3-phenyl-2-propynenitrile and 4-(1-butoxyethoxy)-4-methyl-2-pentynenitrile) and aromatic or heteroaromatic aldehydes (benzaldehyde, 4-CN-benzaldehyde, pyridine-3-aldehyde) to give 3-(2-imidazolyl)-3-aryl-2-acylpropanenitriles, a hitherto unknown family of functionalized imidazole derivatives, in up to 62% yield. This three-component manifold represents a novel C(2)-functionalization of the imidazole nucleus involving zwitterionic, carbene and enol ether intermediates. Unlike the analogous reaction with aliphatic aldehydes, which gives enol ethers, in this case the latter undergo the further rearrangement to 3-(2-imidazolyl)-3-aryl-2-acylpropanenitriles.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide