Applications Of Palladium-Catalyzed Carbonyl Insertion Reaction In The Synthesis Of Bioactive Compounds

Object:Isocoumarins,phthalides and diaryl ketones are an important class of organic compounds widely existing in nature,which have a lot of biological activities.They are also important intermediates to further build other bioactive compounds.Therefore,many medicinal chemists have focused their attention on the synthesis of these compounds.Palladium-catalyzed carbonylative transformations of aryl halides have undergone impressive developments since the pioneering work of Heck and Schoenberg in 1974.In the last four decades,various chemicals such as aldehydes,esters,heterocyclic compounds,etc.have been achieved under CO atmosphere.However,CO is a toxic and flammable gas usually used under the conditions of high pressure.Furthermore,the substrate scope is limited to a small range;all the above drawbacks severely restrict its common applications.In recent years,many researchers intended to introduce versatile CO surrogates in carbonylation processes to displace the use of high toxic and flammable CO.Phenyl formate and isocyanide,a safe and efficient carbon monoxide donor,have been reported.In order to further explore its application,the first part of this paper is to explore the use of phenyl formate as carbon monoxide surrogate to synthesis of isocoumarins and phthalides.In the second part,we explore the use of isocyanide as a carbon monoxide donor for the synthesis of diaryl ketones.Methods:1.By screening the factors that affect the reaction,such as catalyst,solvent,ligand,to find the optimal conditions for Palladium-catalyzed carbonylative synthesis of isocoumarins and phthalides by using phenyl formate as a carbon monoxide source.2.By screening the factors that affect the reaction,such as catalyst,solvent,ligand,to find the optimal conditions for palladium-catalyzed synthesis of diaryl ketones.Result:1 The optimal conditions for the synthesis of isocoumarins and phthalides by using phenyl formate as a carbon monoxide source are substrates,phenyl formate,Pd Cl2(Me CN)2,dppf,Et3 N,anhydrous DMSO.3.The optimal conditions for the synthesis of diaryl ketones by Palladium-catalyzed isocyanide insertion reaction are arylboronic acid,Pd(OAc)2,Cu(OAc)2,anhydrous dioxane.Conclusions:1.In this paper,we have investigated a novel and efficient method for the synthesis of isocoumarins and phthalides,avoiding the use of carbon monoxide.At the same time,the method has the advantages of lower toxicity,milder conditions,easy operation and wide functional group tolerance.2.In this paper,we have successfully developed a palladium-copper-catalyzed oxidative cross-coupling of arylboronic acids with isocyanides for the synthesis of diaryl ketones.This reaction represents an efficient and alternative strategy for the synthesis of carbonyl compounds.