Transition Metal-Catalyzed C–H Activation Reactions And Their Applications In The Construction Of Spiro Compounds

Transition metal-catalyzed C–H activation reactions have become research hotspots in the field of organic synthesis because of their high efficiency,simplicity,atomic economy and step economy.C–H activation reactions could construct a series of novel compounds from simple substrates for drug activity screening quickly and efficiently.Therefore,they have become indispensable tools for medicinal and organic synthetic chemists.In recent years,copper-catalyzed or-mediated C–H functionalization reactions have attracted considerable attentions due to the earth-abundant and low-toxic copper catalysts.The development of copper-catalyzed or-mediated C–H functionalization reactions,have the advantages of reducing the cost,enriching the diversity and increasing the potential of industrial application of C–H functionalization.In this thesis,we main study on copper-catalyzed or-mediated C–H functionalization reactions and rhodium-catalyzed C–H activation tandem cyclization reactions to construct novel structures of spiro compounds.The thesis mainly contains several parts as follows:1.Efficient synthesis of spirooxindole pyrrolones by a Rhodium(Ⅲ)-catalyzed C–H activation/carbene insertion/Lossen rearrangement sequenceIn this work,we developed a Rh(Ⅲ)-catalyzed domino cyclization of acrylamide and diazindole compounds through C(sp~2)–H activation,carbene insertion,Lossen rearrangement,and nucleophilic addition steps to construct spiroindolone skeleton compounds efficiently.The reaction was realized under mild conditions and tolerated with various functional groups.The late diversification of drug molecules further demonstrated the potential utility of this protocol.2.Copper-catalyzed oxalamide-directed ortho C–H amination of anilines with alkylaminesIn this work,we developed a copper-catalyzed oxalamide directed ortho C–H amination of anilines by using 1 atm of air as the sole oxidant.The protocol showed excellent functional group tolerance and some heterocyclic amines including indole,benzothiophene,benzothiazole,quinoline,isoquinoline,and quinoxaline could be compatible in the reaction.In addition,the late-stage diversification of medicinal drugs demonstrated the synthetic utility of this protocol.3.Copper-mediated C-H thiolation of(hetero)arenes using weakly coordinating directing groupIn this work,we developed a copper-mediated C–H thiolation of(hetero)arenes by using monodentate amide as weakly coordinating directing group.This protocol features excellent functional group tolerance and shows satisfactory compatibility with various heterocycles,such as indole,pyrrole,imidazole,pyridine,thiophene,and quinoline.The robust nature of this protocol renders that it has potential value in the synthetic application.