Transition Metal-catalyzed NH-indole-directed C(sp~2)-H Amination

Transition metal-catalyzed C-H bond amination reaction has received extensive attention from organic chemists because it can easily synthesize various biologically active molecules,drug molecules or functional materials.As we all know,indole compounds are the basic units of many natural products or biologically active intermediate molecules.In the past ten years,more and more organic workers have devoted themselves to the C-H bond funtionalization of indole compounds.In this thesis,the transition metal-catalyzed C（sp²）-H amination reaction of 2-phenylindole and7-phenylindole,at the ortho position via NH-indole-directed C-H activation was developed.This provides possibility for further cyclization to synthesize important physiologically active compounds,natural products and drugs containing indole ring structures.The thesis includes the following two aspects:First,rhodium-catalyzed C（sp²）-H amination reaction of 2-phenylindoles or7-phenylindoles with secondary amines via NH-indole-directed C-H cleavage.The reaction of 2-phenylindole and morpholine was chosen as a model case to screen the optimal reaction conditions The optimal reaction conditions are as follows:2-phenylindole（0.2 mmol）,morpholine（0.4 mmol）,[Cp*Rh Cl₂]₂（2.5 mol%）,Ag₂CO₃（2equiv）,Ph CO₂Na（2 equiv）,toluene as solvent,at 90 ^oC for 24 hours under nitrogen atmosphere.The NH-indole-directed C-H functionalization also enabled direct amination of 7-phenyl-1H-indoles by changing toluene solvent to DCM.Salient features of our finding include i)facile access to 2-（2’-amino）phenylindoles as well as7-（2’-amino）phenylindoles;ii)mild reaction conditions;iii)excellent functional groups tolerance.The C（sp²）-H amination reaction of 2-phenylindole with p-toluenesulfonyl azide was also studied.The optimal reaction conditions are as follows:2-phenylindole（0.2 mmol）,p-toluenesulfonyl azide（0.4 mmol）,catalyst[Cp*Ir Cl₂]₂（3 mol%）,oxidant Ag OAc（2equiv）,DCM（2 ml）as solvent,at 60 ^oC for 24 hours under nitrogen atmosphere.To evaluate the effectiveness of the optimal protocol,the scope of the substrates was investigated preliminarily.Further substrates exploration and Late-stage transformations into versatile fused-polycyclic indoles are in progress in our laboratory.