Copper-Catalyzed Oxydifluoroalkylation Of Hydroxyl-Containing Alkenes

The tetrahydrofuran motif is a structural unit of many important compounds,and is widely present in many drug molecules and biologically active substances.This type of compounds has excellent biochemical properties,such as anti-tumor,anti-malaria,antiprotozoa,and so on.The special properties of fluorine in the periodic table of the element make this element often used in molecular modification and design of related drug molecules or natural biologically active substances.In recent decades,various fluorinated reagents have been fully developed and used especially difluoromethylene-containing reagents have been widely used in the field of organic synthesis.The introduction of difluoromethylene can effectively improve the metabolic stability and lipophilicity of the parent molecule.Therefore,the introduction of fluorine atoms or fluorine-containing functional groups into a tetrahydrofuran-type compound has very practical and important significance.In this article,hydroxy-containing olefins are reacted with ethyl difluorobromoacetate or difluorobromoacetamide compounds,using pentamethyldiethylenetriamine(PMDETA)as ligand,sodium carbonate as base,and copper hexafluorophosphate tetraacetonitrile(Cu(CH₃CN)₄PF₆)as catalysis.Through free radical mechanism and intramolecular nucleophilic attack of hydroxyl groups,the efficient construction of a variety of tetrahydrofuran compounds is realized.These products also provide the possibility for the diversified conversion of fluorinated tetrahydrofuran compounds.