Studies On The Functionalization Of 4-Monosubstituted Pyrazolones

Nitrogen heterocycles widely exist in some natural products and synthetic drug molecules with excellent biological activities and unique physical and chemical properties.Pyrazolone is an essential five-membered heterocyclic compound containing two adjacent nitrogen atoms.It is widely used to construct various pyrazole/pyrazolone derivatives with novel structures.It has broad application prospects in pharmaceutical chemistry,pesticides,coordination chemistry,dyes and functional materials.In recent years,the functionalization of pyrazolones to get pyrazolone derivatives with broad-spectrum biological activity and medicinal value has become a leading research topic for chemists.Among many pyrazolone synthons,4-monosubstituted pyrazolones have gradually become a hot research topic due to their multiple reactive sites and easy preparation.Therefore,in this dissertation,a series of methodological studies on the efficient construction of novel pyrazolone and pyrazole derivatives were developed with 4-monosubstituted pyrazolones as the synthons,and the following main research results were obtained:(1)A new method was developed for the asymmetric synthesis of 4-alkenyl substituted pyrazolones.Under the catalysis of quinine-derived squaramide,4-monosubstituted pyrazolones and 1-alkynyl-2-naphthols underwent asymmetric Michael addition reaction,and a series of pyrazolone derivatives containing E,Z-configurations,quaternary carbon chiral centers and axially chiral styrenes were obtained in high yields with excellent stereoselectivity.(2)A new strategy for constructing 4-allenyl substituted pyrazolones was developed.Under the catalysis of Ts OH,4-monosubstituted pyrazolones and propargyl alcohols underwent allenylation reaction,and a series of novel 4-allenyl substituted pyrazolone derivatives were synthesized with high yields.The reaction has the characteristics of simple operation,wide substrate tolerance and easy amplification.(3)A new method for constructing 4-aryl substituted pyrazolones by indirect arylation strategy without metal catalyst was developed.Under the catalysis of Ts OH,a series of4-benzofuranyl substituted pyrazolone derivatives were synthesized by arylation of4-monosubstituted pyrazolones with 2-alkynyl phenols in moderate to high yields.This reaction has the characteristics of simple operation,mild conditions and good substrate tolerance.(4)A new strategy for constructing novel fused pyrazoles was developed.Under the promotion of base,4-bromo substituted pyrazolones and benzofuran-derived azadienes underwent [3+2] annulation reaction,and a series of novel fused pyrazole derivatives were constructed in moderate to high yields.Subsequently,asymmetric [3+2] annulation reaction of4-bromo pyrazolones and benzofuran-derived azadienes was preliminarily explored.The reaction is characterized by simple operation and mild conditions.