Copper-catalyzed Difluoroalkylation And Lactonization Of Unsaturated Carboxylic Acids

γ-Lactone,an important building block in organic compounds,is widely present in natural products and bioactive molecules,including some antibiotics,flavors,antitumor agents,and food additives,etc.It is noteworthy that many extremely simpleγ-lactone derivatives have great biological activity,such as alcyopterosin E and3-butylphthalide（NBP）.Fluorine is characterized by a small atomic size and the highest electronegativity in the periodic table.Introduction of fluorine-containing groups or fluorine atoms into organic molecules can have a significant effect on their physical,chemical,biological,and other properties.Therefore,the efficient synthesis of the fluorine-containingγ-lactone is of great significance in the screening of active drugs.In this dissertation,we have developed one-pot difluoroalkylation and lactonization of unsaturated carboxylic acids using Cu Br as a catalyst,pentamethyldiethylenetriamine as a ligand and as a base,Na₂S₂O₅ as a reducing agent and DMSO as a solvent.The resulting difluoroalkylated lactones can serve as important intermediates for further converted into a variety of potentially bioactive compounds.This protocol has the advantages of mild reaction conditions,a low-cost catalyst,high yields and so on.This strategy provides a new cost-effective method for the preparation of difluoroalkyl-substituted lactone compounds.