Rhodium-Catalyzed C-H Bond Activation For Synthesis Of Nitriles And Indole Derivatives

Cyano group and indole skeleton are key structural motifs in a variety of natural products,pharmaceuticals,functional materials,and bioactive molecules.In addition,they are regarded as highly valuable synthetic intermediates in industry.The development of efficient and convenient methods for the synthesis of aryl nitriles and indole derivatives have attracted considerable attention.In this dissertation,rhodium(III)-catalyzed C-H bond activation for synthesis of aryl nitriles and indole derivatives is described.In the first part,a rhodium-catalyzed aromatic C-H bond direct cyanation with safe,bench-stable,and commercially available dimethylmalononitrile as the cyanating agent has been successfully developed.The subsequent aromatic C-H bond direct cyanation reactions of various nitrogen-containing heterocyclic compounds(0.2 mmol)with DMMN(0.4 mmol)were conducted in the presence of[Cp*Rh(MeCN)3](SbF6)2(5 mol%)and CuO(0.8 mmol)in 1,1,1,3,3,3-hexafluoro-2-propanol(1 mL)at 160 0C for 24 h.Under the optimized conditions,the cyanation of starting materials with various directing groups afforded the corresponding nitriles in 43%-88%yields.This reaction exhibited good functional group tolerance,such as methyl,methoxyl,aryl,and trifluoromethyl.The mechanism study showed that the C-H bond cleavage was not involved in the rate-determining step.In the second part,a rhodium-catalyzed annulation for synthesis of pyrrolo[3,4-b]indoles with maleimides as the starting material has been disclosed.The subsequent annulation reactions of various arylhydrazines(0.2 mmol)with maleimides(0.4 mmol)were conducted using[Cp*RhCl2]2(2.5 mol%),AgNTf2(10 mol%),and Ag2CO3(0.4 mmol)in 1,2-dichloroethane(1 mL)at 90? for 6 h.Under the optimized conditions,the annulation of various hydrazines with maleimides afforded the corresponding products in 45%-95%yields.This protocol showed good functional group tolerance,such as methyl,tert-butyl,methoxyl,aryl,halogen atoms(F,Cl,Br,and I),trifluoromethyl,cyano group,and nitro group.The deuterium kinetic isotope effect indicated that the C-H bond cleavage was involved in the rate-determining step.In the last part,a rhodium-catalyzed annulation for synthesis of indoles with maleates as the starting material has been achieved.The subsequent annulation reactions of various arylhydrazines(0.2 mmol)with maleates(0.4 mmol)were conducted using[Cp*Rh(MeCN)3](SbF6)2(5 mol%),NaOAc(25 mol%),and Ag2CO3(0.4 mmol)in 1,2-dichloroethane(1 mL)at 90? for 3 h.Under the optimized conditions,the annulation of various hydrazines with maleates afforded the corresponding products in 50%-80%yields.This protocol showed good functional group tolerance,such as methyl,methoxyl,aryl,halogen atoms(F,Cl,Br,and I),and trifluoromethyl.The product dimethyl 1H-indole-2,3-dicarboxylate was easily converted to 4-methyl-1H-furo[3,4-b]indole-1,3(4H)-dione,an intermediate for the development of medicines.The mechanism study showed that the C-H bond cleavage was involved in the rate-determining step.