Palladium-Catalyzed Highly Para-selective Difluoromethy Lation Of Aromatic Ketone Derivatives

Transition metal catalyzed C-H bond functionalization is a powerful synthesis method that can economically,efficiently and directly build carbon-carbon bond and carbon-hetero bond.The high regioselectively achieving C-H bond functionalization reaction has always been a rasearch hotspot in the field of C-H bond activation.Regioselective development of para-C-H bond activation of benzene rings currently has no efficient strategy,but only a preliminary nature.Therefore,the development of a para-selective functional group reaction for the benzene ring is an urgent problem to be solved by the organic synthesis method.In this thesis,the weak Lewis acid of the divalent palladium is used to activate the aromatic ring,and the steric hindrance effect of the coordination in the palladium catalyst regulates the activity of different sites of the aromatic ring to achieve the para-difluoromethylation of the aryl ketone and the aromatic ester compound.The main contents of this paper are as follows:First,the para-selective C·H bond functionalization of the aromatic ring is summarized,and the characteristics and research significance of these reactions are also described.Second,We systematically studied the site-selective C-H bond difluoromethylation.reaction of aromatic rings.It was found that the para-difluoromethylation reaction of aromatic ketones can be achieved by using tetrakistriphenylphosphine palladium as the catalyst and triphenylphosphine as the ligand.The reaction is suitable for a wide range of substrates and various functional groups,all of which provide the corresponding para-difluoromethylated product in moderate to good yields.In addition,the difluoromethylene group was successfully introduced into several well-known drugs such as ketoprofen,zaltoprofen,oxybenzone,and chrysazin.The modification method is very likely to improve the activity of these drugs,so it has high research value and application prospect.Finally,we systematically studied the site-selective C-H bond functionalization of aromatic ester derivatives.A palladium-catalyzed,para-difluoromethylation reaction of[1,1'-biphenyl]-2-dicyclohexylphosphine-regulated aromatic ester compounds has been successfully developed.The substrate of this strategy is highly adaptable and is capable of providing the corresponding Para-difluoromethylated product in moderate to good yields.