Studies On The Annulation Reaction Of Sec-N-Arylamides With Olefins And The Synthesis Of Ketones By The Condensation Of Sec-Amides With Tert-Amides

Quinolines are an important category of nitrogenous heterocyclic compounds,which not only widely exist in natural products and drug molecules,but also have very important applications in the fields of synthetic chemistry,pharmaceutical chemistry and material chemistry.As an important synthetic intermediate,there are fewer reports about synthesis of 3,4-dihydroquinolines.Therefore,it is a challenging and important topic to develop high-efficiency organic synthesis methods to construct the structure of 3,4-dihydroquinolines.Ketones are a class of extremely important building blocks with significant reactivity and multiple-reactive sites that can participate in many types of reactions.Such as Michael addition reaction,Wittig reaction and Aldol reaction.However,the current synthesis strategies have some functional group tolerance problems and substrate universality issues.Therefore,it is of great significance to develop a general high-functional-tolerance method for preparing ketones.This thesis contains the following two parts of work:1.Developed a general method for the direct construction of 3,4-dihydroquinoline structures by the annulation reaction of sec-N-arylamides with olefins and its application in nucleophilic addition,reduction and oxidation reaction systems.(Chapter 2)Based on the activation of Tf2O/2-F-Pyr.,a general method for direct construction of 3,4-dihydroquinoline structures by the annulation reaction of sec-N-arylamides with olefins was developed,and the 3,4-dihydroquinolines could be applied in nucleophilic addition(Ugi reaction),reduction and oxidation reaction systems.First,the secondary amides were converted into a nitrile oxime intermediate under the activation of Tf2O/2-F-Pyr..After the nucleophilic addition of the non-activated olefins,the carbons were captured by the intramolecular Friedel-Crafts alkylation reaction,and then 3,4-dihydroquinolines formed.This methods formally correspond to the[4+2]cycloaddition of sec-N-arylamides with olefins2.Developed a general methods for the synthesis of ketones by the condensation of sec-amides with tert-amides(Chapter 3)Based on the activation of Tf2O/2-F-Pyr.and the catalytic system of[Ir]/PMHS,a general method for the synthesis of ketones by the condensation of sec-amides with tert-amides was developed.tert-Amides were catalytic reducted to enamines by[Ir]/PMHS catalytic system,and then reacted with the activated secondary amides,formed intermediate of imine-imidoxime,and then hydrolyzed to give ?-keto aldehydes.The ?-keto aldehydes,with the addition of an acid,removed the aldehyde groups and finally gave the ketones.This reaction has better substrate universality and functional group tolerance.