Cross-coupling Of Enamides And Hydrocyanation Of Alkynyl With Formamide As Cyanide Source

In the 21st century,with the improvement of living standards,people's health and environmental awareness are getting stronger.With the development of organic chemistry,people can synthesize biologically active substances with low content and complex extraction processes in the natural world for the benefit of mankind.Most of the drugs and natural products containing nitrogen atoms,because of their complex structure,should be synthesized in multiple steps.Enamides and nitriles,are important intermediates in organic chemistry,can be easily converted into other compounds.Due to its special structure,enamide can undergo hydrogenation,nucleophilic addition or coupling reaction under transition-metal-catalysis,to obtain a series of chain or cyclic nitrogen-containing compounds.Nitrile compounds have a wide range of applications,and their preparation requires the use of highly toxic cyanide,or the reaction operation is complicated.In order to efficiently and selectively achieve cross-coupling of enamides and find a green and environmentally method to synthesize nitrile compounds,we conducted a series of studies.This dissertation can be devided into two parts:The first part focuses on chemo-and regioselective cross-coupling of two enamides.In the past literature,the cross-coupling reaction of two enamides was less studied,and the yield and selectivity were not very high.Therefore,we wanted to develop a highly efficiency and selectivity scheme for achieving the cross-coupling reaction of two molecules enamide.After system optimization,the optimal conditions were determineded as:Pd(OAc)2 as catalyst and DCE as solvent,reacted in an oil bath at 110 ? under air atmosphere.Compared with previous reports,this method can achieve in better yield and selectivity.The second part mainly studied the hydrocyanation reaction of diphenylacetylene with formamide as the green cyanogen source.The previous literature reported that the use of formamide as a cyanogen source requires the excessive use of toxic POCl3.We envisage using a catalytical metal catalyst to achieve hydrocyanation with formamide as a cyanogen source.After system optimization,NiCl2 and CuCl were used as catalysts,with ligand and Li(OAc)2 as additive.The role of formamide is to provide the source of cyano,as reducing agent and reaction solvent,and the reaction affords excellent yields in air atmosphere.Compared with previous reports,this method is more green and has broad potential application in synthesis.