Copper-Mediated Hydrodifluoroalkylation Of Alkynes

Organic fluorine compounds are widely used in the fields of materials,pesticides and pharmaceuticals,which makes fluorochemistry become one of important research areas in the field of organic synthesis.In the past few decades,the introduction of fluorine atom and trifluoromethyl group into organic molecules has received extensive attention,but the introduction of functionalized fluorine-containing groups has been relatively rare.Difluoromethylene is regarded as a bioisostere of oxygen atom,carbonyl,and methylene,and the introduction of difluoromethylene to organic compounds affects the electronic property,chemical property,and biocompatibility of the parent molecules.Thus,the development of an efficient synthetic method of difluoro-containing compounds is particularly important.We have developed a highly selective copper-mediated hydrodifluoroalkylation of alkynes with N,N,N?,N?-tetramethylethylenediamine as the base and ligand,the functionalized difluoroalkyl reagent as the fluorine source,and Na₂S₂O₅ as the reductant.Na₂S₂O₅ plays an important role in the reaction as an reductant to convert high valence copper to Cu?I?and to suppress the homo-coupling reaction of alkynes as side reaction.This protocol exhibits mild reaction conditions,low-cost catalyst,broad substrate scope,excellent functional group compatibility,and good regio-and stereoselectivities,which provides a straightforward and efficient access to a variety of difluoroalkylated alkenes.