Palladium-catalyzed Intramolecular Coupling Reaction Of Aryl Halide With Alcohol

Palladium-catalyzed C-C bond formations,aryl halides reacting with carbon nucleophiles centered on carbon atom,have the advantage of mild reaction conditions and high functional group compatibility.Successful extension of these reactions to heteroatom nucleophiles including amines and thiols has been achieved.However,the research on palladium-catalyzed coupling of Ar-X with alcohols remains in a subtle and elusive period.Now,available methods for the synthesis of aryl ethers via direct nucleophilic substitution of an aryl halide with an alcohol typically require harsh or restrictive reaction conditions or a large excess of the alcohol and are limited in substrate scope.First of all,this thesis summarizes the research about the transitional metal palladium-catalyzed C-C bond formations,emphasizing all kinds of typical coupling reactions named after famous chemists.The basic concepts,reaction mechanism, general research process and practical application of these coupling reactions, including Heck reaction,Sonogashira reaction,Stille reaction,Suzuki reaction and Negishi reaction,were elaborated one by one.Then,on the basis of mastery of palladium-catalyzed C-C coupling reaction,research process,reaction mechanism and condition of C-Heteroatom(C-N,C-S,C-O)coupling reactions catalyzed by Palladium and other transitional metals,including their great application in synthetic work,are summarized.Although alkoxides are less nucleophilic than amines and thiols,let alone all kinds of 'hard' organometallic nucleophiles,the basic mechanism of inter- and intramolecule coupling reactions is similar.The aforementioned research process on palladium-catalyzed C-C and C-Heteroatom bond formations would be greatly helpful to understand and master all kinds of coupling reactions.Also,it is crucial for us to obtain more effective and efficient methods of inter- and intramolecule coupling, especially palladium-catalyzed intramolecule coupling of aryl halides with alcohols mentioned in this thesis.In Chapter Three,research results of C-N and C-O bond formations by intromolecule coupling reaction have been summarized,then novel formation of 1,3-oxazepine heterocycles via palladium-catalyzed intramolecular coupling reaction is specified.In this process,we optimized reactions conditions and steps of synthesis of aryl ethers,and finally obtained the best conditions for this reaction:Pd(OAc)₂ as a palladium source,1,1'-bis(diphenylphosphino)-ferrocene(DPPF)as the ligand,and K₂CO₃ as base at 80℃in toluene.The products have potential applications as biological and medicinal relevant compounds.