An Alkylation Dearomatization Strategy For The Fluorophenol Compounds

Phenolic compounds is a kind of extremely common and versatile chemical raw materials.Its derivatives have been widely utilized in many fields such as drug research and development,polymer material synthesis,and pesticide development.The construction of quaternary carbon centers are complete while the stereo conversion from two-dimensional plane to three-dimensional molecule in one-step is realize by the dearomatization transformation of phenolic compounds.Since the ortho-position and para-position of the phenolic hydroxyl group are more active,phenolic compounds substituted at the ortho-position and para-position have always received widespread attention from chemists.Based on the mature development of electrophilic halogenation reaction,halogenated phenols can be generally prepare by electrophilic halogenation of simple phenolic compounds.Therefore,it has become a hot issue for chemists to explore the derivatization and conversion of halogenated phenols,which easily obtained.However,since the nucleophilicity of halogenated carbon sites are generally weaker than that of carbon-substituted phenolic compounds,the electrophilic dearomatization of halogenated phenols is more difficult than that of carbon-substituted phenolic compounds.The existing dearomatization conversions of halogenated phenols generally focused on transition metal catalyzed reactions,while electrophilic dearomatization reactions without metal catalysis were report rarely,and most of them were chlorinated phenols,brominated phenols,and iodophenols participated,reactions involving fluorophenols were extremely rare.From the perspective of electronegativity,the electronegativity of fluorine is greater than that of chlorine,bromine,and iodine atoms.This is likely to make the fluorinated carbon site less nucleophilic and increase the difficulties of realize the electrophilic dearomatization conversion.However,look from the volume of the atom shows that the volume of fluorine atom is smaller than that of chlorine,bromine,and iodine atoms.So that the steric hindrance is much smaller,making this conversion possible.Finally,from the perspective of product's stability,the C(sp~3)-F bond is more stable than C(sp~3)-Cl,C(sp~3)-Br,C(sp~3)-I.Wherefore the stability of the dearomatization products of fluorophenol should also be relatively higher than other halophenols'.Thence,the dearomatization conversion of fluorophenols is more challenging than other halogenated phenols while it is also possible to achieve.The main content of the paper includes the following three chapters:Chapter one briefly introduced the potential application prospects of the molecular skeleton of the dearomatization products of phenolic compounds in the field of pharmaceutical molecules,as well as the research progress of the oxidative dearomatization conversion of phenolic compounds in recent years.The second chapter introduced the research process of dearomatization conversion of phenolic compounds in non-oxidative mode in recent years.The conversions had been classified to six types according to the different electrophiles then were elaborated as alkylation dearomatization,alkenylation dearomatization,arylation dearomatization,halogenation dearomatization,amination dearomatization and the dearomatization involving other electrophilic reagents.In the third chapter,the alkylation dearomatization conversion of fluoronaphthol was report.The fluoronaphthol had been utilizd as nucleophile and obtained a stable alkylation dearomatization product under mild reaction conditions without the participation of metal catalysts.The yield showed well as it was also compatible with allyl electrophiles.Unfortunately,fluorophenol was not compatible with this reaction system currently.In addition,we have also explored the mechanism of the reaction while ruled out the possibility of the traditional[3,3]rearrangement path.The specific reaction mechanism needs further exploratio.