A Dearomatization/Dehalogenation Strategy For The Spiroannulation Of Halophenols

As fundermental organic chemical raw materials,phenolic compounds could be easily obtained from various of natural sources.These compounds have been utilized in many fields at the same time,such as medicine development,material creation,and natural product synthesis.According to its structural feature,the hydroxyl group substituted at the ortho-and para-position on the phenol ring could be particularly active and those phenols are easily functionalized and modified.Therefore,ortho-and para-substituted phenolic compounds always play important roles in practical applications.For example,halogenated phenol is one of most commonly substrates.Halogenated phenols are mainly use as a two-dimensional planar organic synthetic building block in the traditional conversion methods.In contrast,using dearomatization to break the aromaticity of the phenol ring at the halogenated site,and to realize the conversion of a two-dimensional planar structure into a three-dimensional molecular skeleton are rarely reported.According this conclusion,this dissertation will start from halogenated phenolic compounds and use dearomatization conversion as the key method,aim to explore a concise,efficient and novel type of chemical conversion.The following five parts are included in main content:The first chapter mainly introduces the reseach progress of phenolic compounds and their basic chemical properties,and dearomatization reactions with traditional methods.The second chapter introduces the recent development on dearomatization of phenolic compounds in non-oxidative mode,and elaborates the chemical conversions of phenolic compounds such as dearomatization-allylation,alkenylation,arylation,arylation,halogenation and amination.In the third chapter,we report one case of dearomatization/debromination spirocyclic reaction involving bromophenolic compounds.Bromophenols were employed as bifunctional single-carbon sources synthesizer in this reaction and realized the rapid construction of the azaspiro-ring molecular framework with gentle and metal-free condition.It is worthy to point out that the reaction has excellent yield and high functional group tolerance.Both naphthol substrates and phenol substrates with functional groups are compatible in the reaction system.In addition,chlorophenols and iodophenols are also tolerated in the reaction system.Moreover,further study of the reaction mechanism was also conducted,which provides a solid theoretical support to the strategy of spiro ring construction of halogenated phenol dearomatization/dehalogenation.In the forth chapter,we use Sc（OTf）₃ and the chiral ligand Py-box as a combined catalyst to achieve the asymmetric control of the dearomatization spirocyclic reaction involving bromonaphthol.This reaction shows good yield and excellent enantioselectivity,which can be used as an important supplement to the catalytic asymmetric dearomatization（CADA）,providing a new solution for the synthesis of drug molecules containing such chiral spirocyclic fragments.In the fifth chapter,we utilize the strategy of spiro ring construction of halogenated phenol dearomatization/dehalogenation.Starting from the fluoronaphthol substrate containing stable carbon-fluorine bonds,utilizeα-βunsaturated imine as the amphiphilic type four-atom synthons through dearomatization and S_RN1 nucleophilic substitution reaction based on radical mechanism,to promote the reverse cleavage of carbon-fluorine bonds.Finally,the spirocyclic conversion of fluorocarbon sites as carbon-synthons could be realized.