In Situ Captured Active Intermediates To Construct Carbon (Hetero) Ring Structures Via [4+2] Cyclization Reaction

[4+2] Cyclization reaction is an important means of efficiently constructing a sixmembered carbon(hetero)ring skeleton.It can efficiently connect atoms in molecules to form a series of circular structures,which can effectively improve the structural stability of organic compounds.It has been widely used in the synthesis of many natural products,pharmaceutical molecules,and organic materials.The [4+2] cyclization reaction strategy can not only achieve rapid and efficient synthesis of complex compounds,but also effectively reduce the consumption of raw materials and production costs.Therefore,studying the [4+2] cyclization reaction and expanding its application in organic synthesis has become one of the research hotspots in the field of organic synthesis.The purpose of this article is to construct carbon and nitrogen ring structures with diverse structures by capturing highly active intermediates such as 2-nitrosobenzaldehyde and aryne generated in situ and causing them to undergo [4+2] cyclization or [4+2]cycloaddition reactions.It mainly includes the following four chapters:In Chapter 1,we investigated and summarized the research progress and applications of [4+2] annulation,[4+2] cyclization,and [4+2] cycloaddition strategies,and introduced their reaction characteristics,reaction mechanisms,application ranges,and existing challenges in detail.This paper proposes a research idea for developing new organic synthesis methods and strategies,which involves in situ generation of corresponding active intermediates through other reaction types,followed by other reagents to capture them and undergo [4+2] cyclization reactions to construct various carbon(hetero)ring compounds,including the preparation of phenanthrene compounds by combining ene reactions with [4+2] cycloaddition reactions.The combination of intramolecular redox reaction and [4+2] cyclization reaction was used to prepare cinnoline and quinazoline derivatives.In Chapter 2,based on the previous work of the research group,we developed a series of ene/[4+2] cycloaddition reactions that capture highly active aryne intermediates in situ.Through the selective addition of aryne,highly selective construction of phenanthrene derivatives can be achieved.Compared to existing non noble metal catalytic systems,this synthesis method can not only achieve lower reaction temperature,shorter reaction time,but also achieve higher regioselectivity,which can meet the synthesis requirements of complex structures and drug molecules.In Chapter 3,we developed a new method for the synthesis of cinnolines without the involvement of transition metals by using 2-nitrobenzyl alcohol as a raw material to produce 2-nitrosobenzaldehyde intermediates in situ through intramolecular redox reactions,and then capturing them with benzylamine to undergo a [4+2] cyclization reaction.The reaction has the advantages of simple operation,no transition metals involved,and a wide range of reaction substrates.In addition,we also synthesized quinazoline derivatives using 2-nitrobenzyl alcohol and benzylamine as raw materials through intramolecular cyclization in dimethyl sulfoxide solution.This method provides a new idea for further research on the reactivity of 2-nitrosobenzaldehyde.In Chapter 4,the summary of this thesis and outlook of future work were given.