Study On The Synthesis Of Lactones Via Copper-Catalyzed Intramolecular Coupling Of Bromoenoic Acids

Lactones are an important class of heterocyclic compounds. The lactone subunit especially containing five-membered ring occurs in a number of natural products. Saturated and unsaturated five and six-membered ring systems containing oxygen are commercially important, with applications in pharmaceuticals, flavours and fragances. Exocyclic enol latones are important synthetic intermediates, and the interest in syntheic methods for preparation of exocyclic enol latones has arisen because of the biological activity, cytotoxic and antibiotic properties exhibited by a number of natural products containing this substructure. Extensive methodolodies for the synthesis of theγ-methylene-γ-lactone by the cyclization of alkynoic acid using silversalts, mercuric salts, and transition metals as catalysts have been reported. The synthesis of lactone via copper-catalyzed coupling of bromoenoic acid was investigated in this paper. It could be described as the following two parts1. Synthesis of lactones by copper-catalyzed intramolecular vinylation of carboxylic acids was investigated for the first time. Through our experments, we concluded that the optimized conditions for this reaction was to use CuI as catalyst, K₂CO₃ as the base, N, N'-dimethyl cyclohexane-1,2-diamine as the ligand, and refluxing THF or CH₃CN as the solvent. These optimized conditions allowed the convenient preparations of 5-membered lactones. The configuration of the double bond was retained under the reaction conditions. It was concluded thatγ-methylene-γ-lactone can be achieved via this method which should be of important application in organic synthesis.2. We also tried to carry out the corresponding 4-exo and 6-exo cyclization reaction of bromoenoic acids, but was unsuccessful so far. Further investigation is required.