Catalyst-Controlled Selective Alkylation/Cyclopropanation Of Indoles With Vinyl Diazoesters

In the related research fields of natural product chemistry and medicinal chemistry,we can often see some structures with indole skeletons,which are also key building blocks for the synthesis of some complex molecules.Carbene transfer of diazonium compounds and indole is the most direct means of synthesizing indole derivatives.The others mostly used indole and aryl diazo esters or alkyl diazo esters with protective groups on N.Under the control of different transition metal catalysts,indole cyclopropanation products,C~2 or C~3alkylation products on the indole ring,and some dearomatization products can be achieved chemoselectively.When using phenylalkene diazo esters,The others used Rh catalysts to obtain a multi-ring connected structure.Based on previous investigations on the functionalization of indole,and out of my own interest in this type of reaction and gold catalysis,this thesis uses different metal catalysts to achieve the functionalization of two indoles,and through experiments And related literature to study its reaction mechanism.This article mainly conducts research and discussion from the following three aspects:(1)Research progress of indole functionalization reaction of diazo compounds through carbene transferThe research progress of using diazo compounds to obtain functionalized indole by carbene transfer is reviewed.For the functionalization reaction of indole,the research progress is described from four aspects:cyclopropanation reaction,C~2-position alkylation reaction,C~3-position alkylation reaction,and dearomatization reaction.(2)Catalyst-controlled selective functionalization of indole and olefin diazoWe have developed a gold-catalyzed selective C~3 alkylation reaction of indole and olefin diazonium.The easy-to-use diazo compound and indole can achieve a yield of up to 85%under mild reaction conditions.The C~3 position alkylation product is obtained;the silver catalyst is used on the other side,and the cyclopropanation product can be obtained with a high degree of non-corresponding selectivity greater than 19:1.The experimental operation is simple and the reaction rate is fast.It only takes 5 minutes.The highest yield is92%to get the target product.(3)Research the reaction mechanism through experiments and related literatureSince the combination of olefin diazonium and different metal catalysts will mainly exist in three forms of resonance,the intermediate structures of the vinyl carbene of gold and silver are different,and the reactivity shown is also inconsistent.The reaction path catalyzed by gold It may be carried out in the form of carbocations;and the reaction path catalyzed by silver may be carried out in the form of carbene.