The Study Of Arene 1,2,3-trifunctionalization From Allyl Sulfoxide And Aryne

Multisubstituted benzenes are ubiquitous among organic functional materials,natural products,and drug molecules.Obtaining the multisubstituted benzene derivatives through simple and effective approaches is one of the important aspects in synthetic organic chemistry.One way to access this multifunctionalization is to utilize the highly reactive carbon-carbon triple bond of an aryne intermediate.The high activity of arynes makes many chemical transformations accessable.Moreover,recent advances in aryne chemistry lead to the syntheses of many molecules with special functional group topology;however,only the ortho-disubstituted products could be constructed from an aryne triple bond.It has not yet been reported to functionalize the aromatic ring with three or more substituents in one operation using a single aryne intermediate.The theme of our group research is to puesue the multifunctionalization of an aromatic ring through new aryne chemistry.In our previous work,we desigened and synthesized a new type of domino 1,2-benzdiyne precursor(TPBT).Using this TPBT reagent,we accomplished several 1,2,3-trifunctionalizations on a benzene ring.Enlightened by this TPBT reagent,we conceived other tandem reactions.By combining the traditional vicinal disubstitution chemistry of a Kobayashi benzyne precursor with a consequent C3-H bond functionalization we were able to achieve the 1,2,3-trifunctionalization of a benzyne intermediate in a cascade sequence.In a three-component reaction system consisting of aryl allyl sulfoxide,Kobayashi aryne precursor,and ethyl bromoacetate,three substituents were incorporated on the same benzene ring.Notably,this protocol generates C-S,C-O,and C-C bonds simulteniously.The reaction conditions were also optimized,which resulted in high yields of the trisubstituted products.In addition,we demonstrated the generality of the method by altering sulfoxides,aryne precursors,and protecting groups.It is worth noting that several benzene derivatives with pentasubstitution were synthesized efficiently,which indicates the potential value of this methodology in drug discovery.Further elaboration of the trisubstituted products exhibits their potential application.In the future,an in-depth study of the mechanism will deepen our understanding on this chemical transformation.This chemical transformation is based on the research of the domino TPBT reagent in the previous work,and the transformation is not only mild reaction conditions,wide range of substrate applications,diversification of product structure,but also breakthrough the limitation of the TPBT reagent using tri-substituted arylalkyne.We can obtain the tri-substituted aromatic products efficiently by using di-substituted mononuclear reagents,which has the advantages of atomic economics.