One-Pot Knoevenagel/Imination/6π-Azaelectrocyclization Sequence for the Synthesis of Disubstituted Nicotinonitriles
Li-Chun Lin1, Sundaram Suresh1, Kun-Wu Lin1
1Department of Chemistry, National Taiwan Normal University, No. 88, Sec. 4, Ting-Zhou Road, Taipei 11677, Taiwan, R.O.C.
Abstract:
We report on a copper-catalyzed three-component reaction for the synthesis of disubstituted nicotinonitriles using 3-bromopropenals, benzoylacetonitriles, and ammonium acetate (NH4OAc). The Knoevenagel-type condensation of 3-bromopropenals with benzoylacetonitriles gives δ-bromo-2,4-dienones that contain strategically placed functional groups that react with the ammonia generated in situ to give the corresponding azatrienes. These azatrienes can then be transformed into trisubstituted pyridines under the reaction conditions via a reaction sequence involving 6π-azaelectrocyclization and aromatization.
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