Palladium-catalyzed Haloalkynylation Reaction Of Bromoalkyne

Bromoalkyne is a cheap and easily available important organic synthon with multiple reaction sites.It can not only be used as the source of alkynyl through metal-halogen exchange,but also can be used to construct polysubstituted olefins and participate in cyclization research through the activation of triple bonds by transition metals.In this thesis,we are devoted to research the cross-coupling reaction initiated by nucleophilic palladization of bromoalkyne catalyzed by divalent palladium.Focusing on the selective formation and capture of alkenyl palladium intermediates,focusing on the highly selective formation process and precise transformation of alkenyl palladium species,a novel nucleophilic palladization reaction model based on the capture and transformation of alkenyl palladium was developed,and finally successfully construct a type of organic molecules containing a novel skeleton of dihaloconjugated enynes,and a kind of polysubstituted fused ring was constructed by carbon nucleophilic palladization reaction mode of bromoalkyne.In which aryl palladium species can be captured by different quenching reagents to construct different types of substituents.The specific content of this thesis includes the following three parts.Chapter 1: The synthesis method of bromoalkyne and the coupling reaction,addition reaction and cyclization reaction in which bromoalkyne participated in recent years are mainly described.Finally,we introduced the research purpose,content and significance of this research topic.Chapter 2: Based on palladium-catalyzed halopalladization reaction of bromoalkyne,we studied the cross-coupling reaction of haloalkyne catalyzed by divalent palladium,and constructed dihalogen conjugated enyne molecule.In dimethylformamide,palladium bromide was used to catalyze the dimerization of bromoalkyne,and a novel organic molecule containing dihalogen conjugated alkyne skeleton was constructed.Furthermore,we have successfully controlled the stability of the alkenyl palladium species formed by haloalkyne and haloalkynol by arranging hydroxyl groups as electron-withdrawing groups and coordination groups at the αposition of triple bonds.During the reaction process,haloalkynol can be used as a quenching agent to quench the alkenyl palladium species formed by haloalkyne,but haloalkyne cannot quench the alkenyl palladium species formed by haloalkynol,so we have realized the selective halogenation of haloalkyne and haloalkynol,two molecules with slight structural differences.By adding lithium bromide or lithium chloride into the reaction system as an external halogen source,dihaloenyne products containing different halogen substitutions can be successfully obtained,and a series of novel and complex haloenyne compounds can be synthesized by the haloalkynylation reaction.The synthesis method has the advantages of mild reaction conditions,good substrate universality and high yield.Chapter 3: In the study of palladium-catalyzed nucleophilic palladization of haloalkynol,the strategy of unactivated aromatic ring as nucleophilic reagent was realized for the first time.When formic acid is used as solvent,palladium bromide catalyzes nucleophilic palladization reaction of haloalkyne to 1,2-carbo palladization reaction.However,in dimethylformamide as solvent,palladium bromide catalyzed nucleophilic palladization reaction of bromoalkynol achieved rare 1,1-carbo palladization reaction through migration rearrangement.Two kinds of nucleophilic palladium reactions are the formation of alkenyl palladium intermediate by carbo palladization of aromatic ring,then hydroxyl dehydration aromatization can be converted into aryl palladium intermediate,and finally different alkyne species can be used to capture aryl palladium to obtain halogenated fused ring products containing allyl and alkyne substitution.