Study On 1,4-Difunctionalization With Benzyne

As a highly reactive intermediate,benzyne has been widely recognized because of its broad synthetic applications in many high value-added compounds.In the early era of this field,however,the benzyne generation conditions were usually harsh,which led to both poor functional-group compatibility and limited reaction modes.Until 1983,Kobayashi's group developed a protocol to generate benzyne under mild conditions,which could in much extend solve the above-mentioned problems.In the past two decades,Kobayashi benzyne precursor has received much attention due to its advantages in expeditious vicinal difunctionalization with diverse combination of various functional groups and its preparation of small molecule drugs as well as natural products.Since 2012,the advances of HDDA benzyne formation protocol developed by Hoye and others have also largely promoted the development of benzyne chemistry.Although benzyne chemistry has made great progresses in recent years,such as nucleophilic addition reaction,pericyclic reaction,transition-metal-catalyzed reaction,insertion reaction,and so on,the current strategies mainly focus on benzyne vicinal difunctionalization.How to break this limitation has become a new and emerging research direction in benzyne chemistry.Our research group previously realized both1,2,3-trifunctionalization and 1,2,3,5-tetrafunctionalization of simple benzyne by combining benzyne insertion reaction to the S=O bond of sulfoxide with subsequent rearrangement transformations.The current project is aiming to accomplish benzyne1,4-difunctionalization,which would provide a new means for the synthesis of natural products and drug molecules containing 1,4-disubstituted benzene ring.In this thesis,we designed and synthesized a series of tertiary amines containing1,3-pentadiene chain structure.When they reacted with different benzyne precursors,1,4-difunctionalized benzenes could be harvested through a sequential N-nucleophilic addition reaction and [5,5]-sigmatropic rearrangement process.This work further broadens the scope of our single benzyne multifunctionalization.