Copper Catalyzed Cross Cyclization Of 1,3-enynes For The Synthesis Of Isocoumarins And Fluorenones

1,3-enynes contain conjugated carbon-carbon double bonds and carbon-carbon triple bonds,so they have multiple reaction sites,strong reactivity,and are commonly substrates for building ring structures.Isocoumarin is a benzo-hexalactone compound,which has many biological pharmacological activities such as protease inhibition,anti-aging,anti-oxidation,anti-proliferation and anti-tumor.Many studies about fluorenones have been carried out in the fields of bioactive molecules,fine chemicals,dyes and liquid crystal materials.The synthesis methods of these two compounds are particularly widely used in drug research,preparation of fine chemicals,synthesis of natural organic products.In this paper,a series of 3-alkenylisocoumarins and fluorenones were synthesized by cross cyclization of 1,3-enynes using copper as catalyst and potassium tert-butoxide as base.There are two conclusions as follows:(1)The cross cyclization reaction between 2-bromobenzoic acids and 1,3-enynes was developed by using copper catalyst,and 22 kinds of 3-alkenylisocoumarins were synthesized in 65%-93% yields.In this system,2-bromobenzoic acids and 1,3-enynes are directly used as substrates,so the reaction steps are shortened,and complex N or P-containing ligands and other additives are unnecessary.The reaction has the advantages of good yield,wide substrate expansion range,suitability for various functional groups,which provides a simple route for the synthesis of 3-alkenylisocoumarin.Moreover,the synthesized products can be modified to obtain valuable bioactive molecules.(2)The cross cyclization reaction of 2-bromoenaminones and 1,3-enynes was developed by using copper catalyst.Twenty-six fluorenones were synthesized in68%-90% yields.In this system,2-bromoenaminones and 1,3-enynes are directly used as substrates,so the reaction steps are shortened,and complex N or P-containing ligands and other additives are unnecessary.The reaction has the advantages of good yield,wide substrate expansion range,suitability for various functional groups,which provides a simple route for the synthesis of fluorenones.Moreover,the synthesized products can be modified to obtain valuable fine chemicals.