Application Of Carboxylic Acid And Pyrrolidone-Directed C-H Activation/Cyclization In The Synthesis Of Nitrogen-Containing Heterocycles

Nitrogen-containing heterocycles respresent an important class of molecular frameworks,and they are widely found in many biologically active natural products,drug molecules and functional materials.Therefore,the development of precise and efficient synthetic methods to construct nitrogen-containing heterocycles with different properties and structures has always been a research hotspot in organic synthetic chemistry.Transition metal-catalyzed C-H bond activation/cyclization reactionshavebeen widely appied in the construction of N-containing heterocycles.Although great progress has been made in this area,the existing synthetic strategies are still insufficient to meet the needs of green chemistry.For example,most chemical reactions require the use of highly coordinated nitrogen-containing directing groups,noble metal catalysts,and equivalent oxidants or additives.Therefore,it is of great research significance to find a more economical,efficient and green synthetic strategy to construct a series of nitrogen-containing heterocycles from simple and readily available raw materials.Aryl carboxylic acids are inexpensive,readily available,easy to store,and environmentally friendly,which making them to be one of the most ideal raw materials in synthetic chemistry.However,due to its stable properties and weak coordination ability,they mediated C-H bond activation/cyclization reactions are often challenging and few reports have been reported to date.Based on this,in this dissertation,we firstly synthesized a series of isoindolinones with diverse structures by using carboxyl group as a directing group in a ruthenium-catalyzed tandem reaction of amine alkylation/cyclization with amine acetal.By screening various reaction parameters,such as solvent,base,reaction temperature,and substrate equivalent,we established the optimal conditions for the reaction,and investigated the substrate scope of aryl carboxylic acids and amine acetals.In addition,we also investigated the reaction mechanism through a series of control experiments and parallel experiments.Subsequently,we used arylpyrrolidones as an effective directing groups for a rhodiumcatalyzed tandem cyclization with stable iodonium ylides to prepare a range of cinnolines and[1,2-a]cinnoline compounds in moderate to good yields.The reaction has the advantages of mild conditions,simple operation and wide substrate scope.In addition,this reaction can be successfully scaled up to a gram scale,and can also be used for the concise and efficient synthesis of other nitrogen-containing fused heterocycles.Finally,based on a series of mechanistic investigations,we propose a possible rhodium-catalyzed [4+2] cylization reaction mechanism for this transformation.