One-Pot Knoevenagel/Imination/6π-Azaelectrocyclization Sequence for the Synthesis of Disubstituted Nicotinonitriles
Li‐Chun Lin, Sundaram Suresh, Kun-Wu Lin, Veerababurao Kavala, Ching‐Fa Yao
Abstract
We report on a copper-catalyzed three-component reaction for the synthesis of disubstituted nicotinonitriles using 3-bromopropenals, benzoylacetonitriles, and ammonium acetate (NH 4 OAc). 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.
Topics & Concepts
Knoevenagel condensationChemistryAromatizationAmmonium acetateSequence (biology)Organic chemistryCatalysisCondensation reactionReaction conditionsAmmoniaCondensationCombinatorial chemistryThermodynamicsBiochemistryPhysicsHigh-performance liquid chromatographyCatalytic C–H Functionalization MethodsSynthesis and Biological EvaluationCyclopropane Reaction Mechanisms