Study On The Construction Of Polycyclic Heterocyclic Compounds Via ?-arylation Of Carbonyl Catalyzed By Copper(?)

?-Arylation reaction of carbonyl compound is such a procedure that the carbonyl compounds with?-H react with aryl halides catalyzed by transition metals which leads to various kinds of?-arylcarbonyl compounds.It is the main method for the formation of C?sp²?-C?sp³?bond,occupys a key role in organic synthesis.In this thesis,the designed aryl halides have also a nucleophilic center,and they can be continuous to undergo the tandem nucleophilic addition cyclization after the?-arylation reaction which may conveniently construct polycyclic heterocylces including imidazo,phenanthridin,quinazolin,chromene.These heterocyclic skeletons are reported to have good biological activity and pharmacological activity,such as Anti-cancer,anti-tumor,anti-inflammatory,analgesic.Therefore,the content of this thesis possesses a important research significance in both organic synthesis and pharmaceutical chemistry.In chapter one,the significance of the subject for this thesis,the?-arylation reaction catalyzed by transition metals including palladium,nickel and copper were introduced in breifly.The innovative points and research methods were also put forward in the first chapter.In chapter two,the reactions of 2-?2-bromophenyl?imidazoles and cyclic1,3-dicarbonyl compounds were studied using CuI as the catalyst to synthesize multiple series of fused heterocylces including imidazoquinolines,imidazolidinones and imidazofilines.All products were charactrized by NMR,IR and HRMS.The structure of product 8c was further confirmed by single crystal X-ray diffraction analysis.This reaction went throught the subsequent?-arylation reaction,nucleophilic addition cyclization,and dehydration process.In the following chapter,the copper?I?was also found to be able to catalyze the?-arylation of 2-?2-bromophenyl?quinazolinones and cyclic 1,3-dicarbonyl compounds.Of which,the six-membered rings including dimedone and piperidine-2,4-dione gave thespiro-isoindoloquinazolinederivativesunexpectedly,whilethe cyclopentane-1,3-dione afforded the normal isoquinolinoquinazolines in high yields.The novel product of cyclohexylspiro-isoindoloquinazoline 10f was further confirmed by X-ray diffraction analysis.A possible reaction mechanism including twice oxidative additions and twice reductive eliminations was put forward according to the product structure.Thereactionmechanismofcyclopentane-1,3-dioneinvovling2-?2-bromophenyl?quinazolinone reaction was the similar to that of imidazole which was discribed in the second chapter.In chapter four,the?-arylation reaction of 2-bromobenzoic acid and1,3-cyclohexanedione was studied to give benzochromene derivatives via controlling the reaction under inert gas atmosphere.If the reaction was carried out uder O₂atmosphere to provide the structurally diversified benzochromene derivatives,it was able to be realized regioselective and partial oxidation by regulating the substituents on the cyclohexane-1,3-dione.Of which,a specific position of cyclohexane-1,3-dione without double substituents underwent a partial oxidation,dehydration and enolization to afford a series of phenochromene derivatives.The regioselective oxidation product of15c was confirmed by X-ray diffraction analysis.If 2-bromobenzamide was submitted to react with dimedone under the same reaction conditions,the dimedone did not involve in this conversion but to give biphenyl bisamides which was generated from two molecules of 2-bromobenzamides via a homocoupling dehalogenation reacion.The product of 18n was also confirmed by X-ray diffraction analysis.The reaction mechanism was the same as that of Ullmann reaction catalyzed by Cu.