Study On Aerobic Copper-catalyzed Intramolecular Cascade Oxidative Isomerization/[4+4] Cyclization Of 2,2′-Disubstituted Stilbenes

5,10-heteroatom contained tetrahydroindeno[2,1-a]indenes including benzofuro[3,2-b]benzofurans,bisindolines(vicinal diamine-type),and others with5,10-heteroatom substitutions represent a class of biologically and catalytically important small molecules.Demands for chemical preparation of these compounds have been grown dramatically.Synthetic approaches to benzofuro[3,2-b]benzofurans have been achieved by stepwise oxidative cyclization of 2,2′-dihydroxystilbenes using chiral Ru(salen)catalyst or stoichiometric amounts of DDQ,Cu(I)/Cu(II)-mediated intramolecular double Ullmann coupling of 1,2-bis(2-bromophenyl)ethane-1,2-diols,nd other methods.In addition,cationic mechanism involved Pd(II)/Pd(IV)catalytic cycle or Cl~+/I~+have been successfully applied to the preparation of bisindolines or thereof with 5-oxo substitution.However,besides the limited reaction scope,noble metal like Pd and Ru,stoichiometric amounts of additional bases,hazardous by-products such as hydroquinone,Ph I,etc.,multiple reactants(more than three components),volatile or toxic solvents such as Me CN,DCM,toluene,etc.,and high reaction temperature(>100~oC)were inevitable in these cases.Given that more and more appeals of sustainable synthesis methods have been raised from chemical society,procedures that can avoid expensive metal catalyst,deliver less or no harmful by-products,simplify the operations,and react at ambient temperature and pressure remain to be highly pursued.Herein,we developed the aerobic copper-catalyzed intramolecular cascade oxidative isomerization/[4+4]cyclization reaction of 2,2-disubstituted stilbene,which can easily synthesize various 5,10-hetero-containing Atomic tetrahydroindeno[2,1-a]indene,and the mechanism of this reaction has been studied.The oxide-tive cyclization reaction is carried out through the common(Z,Z)-diolefin ketone intermediate,which is not specific to the Z-or E-configuration of the substrate,and it is found that the bicyclic product has thermal preference,while the monocyclic product It may be the result of protonation through the(Z,Z)-diolefin ketone intermediate.And the reaction takes place in the following ways:i)using of inexpensive Cu Cl/N,N’-di-tert-butylethylenediamine(DBED)catalytic system avoids precious metal catalysts;ii)the reaction is mild at ambient temperature and pressure;iii)water is the only by-product;iv)a wide range of substrates,suitable for a variety of aryl mono-substituted stilbene substrates and di-substituted stilbene substrates(2a-2ai)of various oxygens.At the same time,it is also suitable for stilbene molecular nitrogen hetero(2aj-2ak)and thia substrates(2al)and large sterically hindered substrates(2am-2an),which has shown a good functional group tolerance and will have a broad application prospects.Our findings provide an important supplement to the oxidative cyclization catalyzed by aerobic copper.