Investigation Of Cyclohexenones In Cross-coupling Reactions And Its Application In The Synthesis Of Phenol Derivatives

Functionalized phenol derivatives are very important chemical intermediates which are widely used in the preparation of drugs,pesticides,polymers and fine chemicals.Consequently,the selective synthesis of phenol compounds with controllable regio-and site-selectivity has been becoming a research hotspot in organic synthesis and attracted extensive attention from organic synthetic chemists.However,its development has faced much challenges due to the intrinsic properties of phenols.First,relatively strong acidity and nucleophilicity of the hydroxyl group of phenols resulted the reaction occurred at hydroxyl group rather than the phenyl ring.Secondly,During the electrophilic substitution process,ortho and para products were usually obtained because of the strong directing effects of hydroxyl group.Third,as an analogues to electron-rich arenes,phenols are sensitive to the strong oxidative reaction conditions which led to a decomposed mixture.In this thesis,we developed a dehydrogenative coupling reaction between heteroarenes?thiophene,furan?and cyclohexenone to form?-heteroaryl cyclohexenone compounds via palladium-catalyzed C-H activation.Subsequent dehydrogenation of produced coupling product safforded meta-heteroaryl substituted phenol derivatives.My thesis includes the following three sections:?1?We summarize the tradition synthetic methods of phenol derivatives,including aromatic electrophilic substitution;transition metal catalyzed hydroxylation reaction;oxidative dehydrogenation of cyclohexenones.?2?We develop a facile approach for the preparation of?-heteroarylated cyclic enones through Pd catalyzed C-H activation by using cyclic enones as the coupling partner.After a series of experiment parameters investigating,we established a novel catalytic system for this dehydrogenative coupling reaction.Our protocol represents outstanding regio-selectivity at the?-position of thiophene moieties and excellent functional group tolerance.Based on the isotope labeled intermolecular competition experiment,we proposed a possible mechanism cycle for such reaction.Finally,the synthesized products were characterized by NMR,mass spectrometry and other instrumental tests.?3?To further exploration the applications of produced coupling products?-thienyl cyclohexenones,we developed an electron-rich palladium catalyst that enabled meta-phenols formation from oxidative dehydrogenation of?-functionalized cyclohexenone.The obtained meta-substituted phenol derivatives were characterized by ¹H NMR,¹³C NMR and high resolution mass spectrometry.