Studies On The Construction Of Cyclopentene-fused Dihydrocoumarins Via Phosphine-catalysed Domino Reactions And Its Mechanism

Organosphosphine-catalyzed cyclization reactions have attracted a widespread attention from scientists because of its efficient bonding mode,high atomic economy,mild reaction conditions,simple operation and environmental friendliness,and have become a powerful tool for the construction of diverse cyclic compounds nowadays.In recent years,the Domino reaction mode has shown great promise in the field of drug synthesis due to its ability to form multiple chemical bonds and assemble complex cyclic molecules quickly and efficiently from simple and readily available raw materials without the need for intermediate separation.Therefore,the development of more economical,environmentally friendly,efficient and rapid phosphine-catalyzed Domino assembly methods is particularly favoured.Accordingly,this thesis summarises the experimental and mechanistic research work on the participation of phosphine-catalyzed allenoate and alkynoates in Domino annulation,leading to the design and completion of the following two aspects of research.In the first part,the organophosphine-catalyzed Domino reaction for the construction of cyclopentene-fused dihydrocoumarin derivatives was successfully achieved using inexpensive and readily available activated methylene compounds and 2-formylphenyl alkynthene as substrates.The strategy is characterized by mild reaction conditions,simple and easy availability of raw materials,synthetic simplicity,excellent substrates applicability and high efficiency in one-pot,which has good application prospects.Moreover,the development of this synthetic method provides an efficient solution for the organophosphine-catalyzed synthesis of coumarin derivatives.In the second part,the detailed mechanism of the organophosphinecatalyzed Domino annulation of 2-formylphenyl alkynthene with reactive methylene compounds is investigated using density functional theory(DFT).Based on controlled experiments and literature research,two possible reaction pathways are proposed: [3+2] or [4+1] cyclisation.The results show that the [4+1] cyclisation process has a lower reaction energy barrier and the key intermediates in it are supported by experimental results as possible reaction pathways.The results facilitate a better understanding of the mechanism of this reaction and provide guidance for the application of this synthetic method and the design of similar reactions.