Remote C-H Bond Arylation On C(5) And C(4) Position Of 8-amide Quinolines

In the past ten years,quinoline compounds as a common nitrogen-containing heterocyclic structure in natural products have attracted the attention of researchers.It is not only a common skeleton in many bioactive mo lecules,but also can be used as a directing group or ligand to participate in various organic reactions.Besides,It can also be used as a fluorescent probe to detect metal ions such as Fe³⁺and Zn²⁺,and can even be used in the fluorescent imaging in biological living cells.In view of the above various applications,the modification of hydrocarbon bonds at various sites of quinoline ring is particularly urgent.However,because of the electron effect of quinoline ring itself,the selectivity of each site is difficult to be controlled,so the selectivity of quinoline functionalization at C?5?or C?4?site is still a challenge.In the second chapter,we developed a metal-free bromination of8-aminoquinoline scaffolds on the C?5?position.This bromination can be followed in a one-pot manner to synthesize substituted quinoline on C?5?position with five kinds of C-X?X=C,O,S?cross-coupling reactions.By using 8-amide quinoline as the guiding group,the corresponding arylated products can be obtained in high yield,and the reaction can be applied to?hetero?aryl boronic acid,alkyl and aryl amide quinoline compounds.In addition,the brominamide quinoline platform molecules were used directly in the reaction,and the alkylation,alkynylation,etherification and aryl etherification of quinoline at C?5?position were obtained by one-pot method.Thus,this developed method shows high practical potential in industrial organic synthesis.In the third chapter,a nickel catalyzed arylation at C?4?site of quinoline was developed.The reaction also uses 8-amide quinoline group as the guiding group,and the aryl Grignard reagent is used as the aromatic source with high regioselectivity to form the C?4?arylation product.Besides,The reaction has good functional group applicability.