Organic Catalyzed Direct Difluoroalkylation Of Tetrahydroisoquinolines

The introduction of fluorine atoms or fluorine-containing groups into organic molecules will significantly alter their original physical and chemical properties as well as biological activities owing to the unique properties of fluorine atoms.Fluorine-containing organic compounds have therefore been widely used in the research fields of medicine,pesticides,and materials.Various alkyl groups could be introduced on the carbon atom of the difluoromethylene group,resulting the structural diversity of difluoroalkyl compounds,thus making them useful in drug research.Therefore,the synthesis of difluoroalkyl compounds has attracted much attention from organic chemist.It is an important method for synthesizing difluoroalkyl substituted compounds based on fluorinated building block,because it avoids the formation of C-F bonds,and has the advantages of good selectivity,mild reaction,and high yield.In the introduction part of the thesis,we classified and summarized the development status of difluoroalkylation reaction according to the different properties of difluoroalkylation reagents.Tetrahydroisoquinoline(THIQ)represents an important type of "privileged skeleton",which is widely exist in many natural products and bioactive molecules.Among them,the C1-substituted THIQ compounds have broad-spectrum biological activities and show good application value in the field of pharmaceutical research.Based on the new difluoroalkylation reagent(difluoroisoxazolacetophenone)developed previously by our group,we developed herein an organocatalytic oxidation difluoroalkylation of N-aryltetrahydroisoquinoline.This method has many advantages,such as no need of metal catalyst,use of air as oxidant,mild reaction conditions,cheap and readily available raw materials,and wide substrate scope.which makes it have potential applications in drug research.