Efficient Construction Of Functionalized Benzofurans And Iminocoumarins Via Cascade1,4-Addition/Intramolecular Annulation Of O-Hydroxyphenylpropargylamines

As multiple reactive sites and highly reactive organic species,ortho-quinone methides（o-QMs）have been focused by chemists and extensively studied and applied in organic synthesis,materials chemistry,and biology since 1907.In addition to o-QMs,alkynyl o-quinone methides（o-AQMs）can be used in even more complex tandem reactions to construction of oxa-heterocyclic scaffold.Based on the previous research of our group,this thesis firstly reviewed the recent advances in the application of organic reactions involving o-QMs.Then,the cascade annulations for the synthesis of functionalized benzofurans and iminocoumarins from imidazolium methylides,β-（methylthio）-β-enamino ketones,and arylsulfonyl radicals with ortho-hydroxyl propargylamines as o-AQMs precursors.The detailed research described as follows:Part Ⅰ:An efficient double 1,4-conjugate addition/intramolecular annulation cascade reaction between propargylamines and two equivalents of imidazolium methylides for construction of structurally versatile dibenzofurans in the presence of KO^tBu/KOH in acetonitrile at 80℃ for 3 h.This transition metal-free protocol proceeds smoothly under bench-top air atmosphere and offers easy manipulation of substituents on the dibenzofuran core,and also provides good to excellent product yields with good functional group tolerance.In addition,a possible mechanism was proposed through the control experiments and detected intermediates.Furthermore,the strategy presents an efficient approach to diversify fluoreno[2,1-b]benzofurans by late-stage functionalization by solvent-oriented intramolecular annulation.Part Ⅱ:With a cascade 1,4-conjugate addition/intramolecular 5-exo-dig annulation between alkynyl o-quinone methides,in which they are generated in situ from propargylamines,and arylsulfonyl radical derived from aryldiazonium salts with DABSO,a variety of 3-arylsulfonyl-5-diazenyl benzofurans are assembled in moderate to good yields under catalyst-and additive-free conditions.In addition,various substituted aromatic alkyne substituents proceeded well affording the desired products as well as the alkenyl-,thienyl-and alkyl containing substrates.For aryldiazonium salts,substrates bearing with mono-or multi-substituents,such as electron-rich（-Me,-OMe）and electron-deficient group（-F,Cl,Br,-CN,-CF₃）,were well proceeded under the optimal conditions,giving the corresponding products in moderate to excellent yields without the substituents effect of electronic and steric hindrance.Moreover,a possible mechanism was proposed by some control experiments.Part Ⅲ:A novel and efficient strategy for the formation of iminocoumarins has been developed via Lewis acid-catalyzed cascade 1,4-conjugate addition/intramolecular nucleophilic substitution/1,5-H shift of o-AQMs withβ-（methylthio）-β-enamino ketones used as the nucleophile in the undried acetonitrile as solvent.It is important to show that functionalized 4-vinyl coumarin was obtained in undried acetonitrile while the 2-amino-4-alkynyl chromene product isolated in dried same solvent by using N-alkylβ-enamino ketone substrate.Furthermore,this versatile method is also found to be applicable to the preparation of a potential bioactive pyrano[3,4-c]chromene skeleton via a one-step subsequent functionalization under mild conditions.In conclusion,a novel and efficient protocol for the formation of functionalized benzofurans and iminocoumarins has been developed through cascade 1,4-conjugate addition/intramolecular annulation of various nucleophiles to o-AQMs as the key intermediate in situ from propargylamines under Lewis acid,base or thermal conditions.The new protocol features good functional group tolerance as well as mild reaction conditions and a broad range of substrate scope,which provided a new and highly efficient strategy for the construction of oxa-heterocyclic scaffold.