| Quinoline and its derivatives are important skeletons in many natural compounds.Most of these compounds have important biological activities and play an important role in new structural entities for medical applications.Quinoline compounds are also widely used in the field of organometallic coordination and optoelectronic materials.At present,the traditional method for synthesizing quinoline derivatives with different substituents is mainly a cyclization condensation reaction.However,harsh reaction conditions and low efficiency limit the application of cyclization reactions.Although transition metal-catalyzed redox coupling reactions have provided a more convenient way to construct quinoline derivatives at the C3 position,the limitation of this type of reaction is that the quinoline substrate needs to be pre-functionalized and requires the use of noble metal catalysts.In recent years,the research on the direct functionalization of quinoline C-H bonds has been rapidly developed,especially the direct functionalization of C2 and C4 C-H bonds of quinoline.For the more challenging C-H bond at the C3 position of the quinoline,the research progress on the functionalization of the C-H bond at the C3 position of the quinoline is slow.Based on our previous research group on the functionalization of quinoline compounds,this article is devoted to the functionalization of the C-H bond at the C3 position of quinoline compounds with high regioselectivity.In the second chapter of this thesis,the highly regioselective aryl formylation reaction of quinoline compounds at the C(3)position catalyzed by nickel catalyst was realized.In this method,aromatic formaldehyde is used as the acyl source,and nickel diacetylacetonate is used as the catalyst,and the conditions are mild and the reaction time is short.The reaction system is suitable for various functionalized quinoline and aryl formaldehyde compounds,with excellent functional group compatibility,such as halogen,ester group,cyano group and silane functional group.The system can also be applied to the late functionalization of complex gemfibrozil derivatives.Mechanism studies indicate that the reaction may be the formation of key anionic complexes by quinoline under the action of alkyl Grinnard reagent.In the third chapter of this thesis,the high regioselectivity of the aryl methanation of quinoline compounds at the C(3)position catalyzed by nickel catalyst is realized.The method uses quinoline and benzyl bromide as substrates,nickel trifluoromethanesulfonate as a catalyst,and Grignard reagent as an additive to obtain quinoline benzylation products.The reaction system is suitable for different substituted quinoline and aryl benzyl bromide,with excellent functional group compatibility,and functional groups such as halogen,trifluoromethyl and cyano are compatible.Heterocyclic 3-bromomethylthiophene can also obtain corresponding compounds in moderate yields.The system can achieve 10 mmol gram scale amplification and can be applied to the functionalization of intermediates of sartan drugs. |
