Study On The Synthesis Of Lactone Via Copper-Catalyzed Coupling Of Bromoenoic Acid

Lactones are an important class of heterocyclic compounds. The lactone subunit especiallyγ-lactone occurs in a number of natural products. Saturated and unsaturated five and six-membered ring systems containing oxygen have commercially important, applications in pharmaceuticals, flavours and fragances. Exocyclic enol lactones are important as synthetic intermediates, and interests in synthetic methods for their preparation have arisen because of the biological activity, cytotoxic and antibiotic properties exhibited by a number of natural products containing this substructure. Extensive methodologies for the synthesis of theγ-methylene-γ-1actone by the cyclization of alkynoic acid using silversalts, mercuric salts, and transition metals as catalysts have been reported.The synthesis of lactones via copper-catalyzed intermolecular coupling of bromoenoic acid was investigated in this paper. Many factors which affect the reaction, such as the reaction temperature, the reaction time, catalyst, base, ligand, as well as solvent were studied for the ring-closure reaction.Under the nitrogen atmosphere, the reaction conditions were optimized. Thus, 10 mol% CuI as the catalyst, 20 mol% N, N'-dimethylcyclohexane-1, 2-diamine as the ligand, the reactions of 4-bromo-2-phenyl-pent-4-enoic acid in refluxing THF, led to the convenient formation of the corresponding 4, 5-dihydro-5-methylene-3-phenylfuran-2(3H)-one in good yields via a 5-exo ring closure.With the optimized conditions in hand, we then examined the scope and limitation of this methodology.