Palladium Catalyzed C-H Activation Tandem Reaction And Fluoroalkylation Of Alkenes And Alkynes

In this thesis,palladium catalyzed C-H activation tandem reaction and fluoroalkylation of alkenes and alkynes have been studied systematically,including the following six chapters:Chapter One:In the first chapter,the types and chemical properties of five membered carbon palladium rings were summarized,and the palladium/norbornene（Pd/NBE）chemistry field was systematically introduced with five membered palladium rings as clues,which mainly divided the following four parts:（1）The historical origin of Pd/NBE chemistry and the early discovery of Catellani reaction;（2）“Ortho effect”;（3）Study on the mechanism of Catellani reaction,and improvement of the reaction system based on the results of mechanism study;（4）Development of electrophilic and nucleophilic reagents for Catellani reaction.Chapter Two:4-Aminoindoles are heterocyclic molecular skeletons with a wide range of biological activities.In this chapter,we synthesized highly functionalized C4-aminated indoles by three components cross-coupling reaction,which utilized both Catellani reaction and retro-Diels-Alder reaction strategy.Based on density functional theory（DFT）calculations,we speculated that the intramolecular Buchwald coupling reaction mechanism undergoes the process of dearomatization and 1,3-palladium migration.According to the energy barrier of the transition state,the reason why tertiary butyl of o-iodoaniline controlled the regioselectivity and chemoselectivity was confirmed.In addition,this method was used to synthesize C4-piperazine indole and GOT1 inhibitor.Chapter Three:Inert C（sp³）-H bond activation has become an important research field in organic chemistry.In this chapter,we developed a carboxylic acids ligand exchange amination/C（sp³）-H arylation reaction using Pd/NBE reaction strategy.Using pivalic acid as a carboxylic acid additive,the inert C（sp³）-H activation was effectively promoted without affecting the key ANP intermediate process.Chapter Four:Spirodihydroindenones is a kind of spirocyclic skeleton structure with biological activity,which widely exists in natural products and drug molecules.In this chapter,we introduced a new Pd/NBE co-catalyzed C-H alkylation/ketone arylation reaction to synthesize spirodihydroindenones in one step.Chapter Five:This chapter systematically introduced two types of fluoroalkylation reagents,electrophilic fluoroalkylation reagents and nucleophilic fluoroalkylation reagents,as well as their application in the fluoroalkylation of alkenes and alkynes.Among them,the representatives of electrophilic fluoroalkylation reagents are Umemoto reagent,Togni reagent,halofluoroalkylation reagent and fluoroalkylsulfonyl reagent,and the representatives of nucleophilic fluoroalkylation reaction reagents are silicofluoranyl reagent and fluoroalkylsulfinates reagent.Chapter Six:This chapter introduced a three-component difluoroalkylation and trifluoromethylthiolation/trifluoromethylselenolation of alkynes and alkenes.In this reaction system,we used air stabled bpyCuSCF₃ and bpyCuSeCF₃ as free radical initiators of ethyl iodidifluoroacetate.This method can effectively inhibit theβ-proton elimination byproduct in the difluoroalkylation of olefins under the thermal catalysis,so that the reaction system has the advantages of both thermal catalysis and photocatalysis.