Research On The Addition Of Phthalazine Salt To Terminal Alkyne

The simple and efficient construction of C-C bonds has always been a central and difficult issue in organic synthetic chemistry.Imine compound addition to terminal alkyne is an important type of coupling reaction.Phthalazine can be treated as a special cyclic imine compound since it contains two conjugated C=N bonds.Propargylamine,which is the additive product of Phthalazine salts and alkynes,not only has good bioactivity on its own,but is also a vital precursor used to synthesize numerous natural products and medicines.This thesis mainly investigates the reaction of phthalazine salts and terminal alkynes under the conditions of transition metal catalysis,including following contents:Initially,the reaction conditions were optimized by screening such as time,temperature,solvent,and type of transition metal catalyst to enable the yields of template substrates to reach up to 87%.Then,a total of 28 products of propargylamine with different substituent groups were synthesized under optimal conditions to give moderate to excellent yields.This reaction not only has good reactivity with both aromatic alkyne and aliphatic alkyne,but also can efficiently obtain the desired products from phthalazines with different substituent groups.It indicated that the reaction has good compatibility with vairous groups and further confirmed the crystalline structure of the product via X-ray diffraction;Finally,the asymmetric synthesis conditions of propargylamine were optimized by screening the chiral ligand,inlcluding bioxazoline compound,pyridine-bioxazoline compound,amino acid and quinine natural products.The ee value of the product was increased to 64% and the yield was 75%.This method provides new ideas and directions for the asymmetric synthesis of propargylamine.Additionaly,this novel product molecule combines the pharmacological frameworks of phthalazine and Propargylamine and it is expected to exert their dual structural characteristics,which can greatly enhance the bioactivity of this molecule and broaden the way for the development of new drugs.