One-Pot Enantioselective Michael-Aldol Approach to Imidazole Derivatives

Significance

Reported is the highly diastereo- and enantioselective one-pot Michael-aldol reaction of α,β-unsaturated aldehydes 1 with imidazoles 2 to give fused heterocycles 3. The reaction is proposed to proceed first via an intermolecular Michael addition, followed by an intramolecular ­aldol reaction. Both steps are mediated by the same organocatalyst. Aromatic α,β-unsaturated aldehydes participate efficiently in the reaction, regardless of electronic character and substitution pattern. Aliphatic aldehydes gave inferior results (65-67% yield). High yields of products were also obtained irrespective of substitution on the imidazole fragment. Excellent diastereo- and enantioselectivities were observed in all cases, and the absolute configuration of one example was proved by X-ray crystallographic analysis. A mechanism is proposed without evidence.