Study On The Palladium-Catalyzed Oxidative/Reductive Heck Coupling Of Thiophenes And Cyclic Enones

In recent years,the transition metal-catalyzed activation of carbon-hydrogen bonds has become a powerful synthetic tool,which has been widely used in the synthesis of natural products,pharmaceutical molecules and polymer functional materials.Due to its atom-and step-economic fashion,it has attracted widespread attention.Among them,the cross coupling reaction of arene with alkene,which is called Fujiwara-Moritani-Heck reaction or oxidative Heck reaction,has been extensively studied.However,the reductive Heck reaction still remains undeveloped yet.The reason to the daunting challenge of reductive Heck reaction is intrinsic syn-?-hydride elimination of the key alkly-Pd-X intermediate,which ultimately results in oxidative Heck coupling products.In this thesis,we report a catalytic system to enable oxidative / reductive Heck reactions of cyclic enones with thiophene or furan derivatives,which are commercially available starting materials.Through concise trapping the alkyl-palladium-enolate intermediates,we develop a controllable oxidative / reductive Heck reaction between cyclic enones and thiophenes.My thesis includes four chapters,which are described as follows:The first chapter summarizes the development of oxidative Heck coupling and reductive Heck coupling in recent years,including the advantages and limitations.Based on our previous research on palladium-catalyzed thiophenes and cyclic enones,the research topics of this thesis are proposed.In the second chapter,we investigate the reductive Heck coupling reaction between thiophene,furan derivatives and cyclic enones.After screening various parameters,the optimized reaction condition was established.Then we study the substrate scope,scale up reaction and late-stage modification of the product to demonstrate the utility of our protocol.In addition,isotope labeling experiment was also conducted to understand the reaction mechanism.It would not only provide a new method to construct various value-added ?-heteroarylated cyclic ketones,but also shed light on developing other conjugate addition reactions via C-H activation.In the third chapter,we investigate the oxidative Heck coupling reaction between thiophene,furan derivatives and cyclic enones.After reaction conditions optimization,substrate scope examination,and scale up experiments,this oxidative Heck coupling reaction is established.This methodology proved to be an economic,environmentally friendly protocol to construct various value-added ?-heteroarylated cyclic enones.Finally,we comprehensively summarize our thesis in the last chapter.