Domino synthesis of functionalized pyridine carboxylates under gallium catalysis: Unravelling the reaction pathway and the role of the nitrogen source counter anion

Abstract

The catalytic potential of various metal Lewis acid catalysts have been assessed to derive a high-yielding, multi-component domino synthesis of functionalized pyridines from (E)-3-(dimethylamino)-1-aryl/heteroaryl-prop-2-en-1-ones, 1,3-dicarbonyl compounds, and an ammonium salt (as the nitrogen precursor). Amongst the various metal halides, tetrafluoroborates, perchlorates, and triflates used as the catalyst, GaI3 proved to be the most effective. The mechanistic course of the most plausible pathway has been outlined as the intermediate formation of imine/enamine by the reaction of the 1,3-dicarbonyl compound with ammonia (liberated in situ from the ammonium salt used as the nitrogen source), which participates in the domino nucleophilic Michael reaction to the (2E)-3-(dimethylamino)-1-aryl/hetroarylprop-2-en-1-one by its active methylene carbon through its enamine form followed by intramolecular cyclization and aromatization. The effect of different ammonium salts as the nitrogen source has been investigated and NH4OAc was found to be best. The influence of the acetate counter anion of NH4OAc on the progress of the reaction was studied and its specific role in the cyclization and subsequent aromatization has been revealed. This work offers distinct advantages compared to the literature reported methodologies on the count of several green index parameters.