Study On Rhodium Catalyzed C–H Activation For Cyclic Synthesis Of Isoquinoline

Over the past few decades,transition metal-catalyzed C–H functionalization reactions have become one of the most powerful tools for the construction of complex molecules.In particular,the C–H activation/cyclization strategy has attracted a great deal of attention because its ability to form complex cyclization products directly from simple feedstocks.At present,researches based on C–H activation/cyclists have made great progress.However,this field is still in its infancy,and the development of new reaction types and systems for substrates remains to be expanded,and the mechanism of the reaction also needs to be further studied.In the coming years,research in this area is likely to involve asymmetric cyclations,while other metal catalysts or green solvents that are cheaper than Rh/Ru or Pd are also being explored.Based on the advantages of C–H activation/cyclization reaction,this paper studied the RH-catalyzed C-H activation and cyclization reaction using oxime and 2-phenyl quinazoline-4（3H）-ketone as substrates.At the same time,the application of some green solvents in this kind of reaction is investigated and the concrete conclusions are as follows:（1）The rhodium-catalyzed C–H activation and cyclization of oxime and alkynes with oxime as substrate were studied.The effects of different solvent catalyst additives and temperature on the reaction yield were investigated.The results show that the optimal reaction condition is:ketoxime（1 equiv）,alkyne（1 equiv）,Dichloro（pentmethylcyclopentadienyl）rhodium（III）dimer（[Cp*Rh Cl₂]₂）（2 mol%）,Silver Hexafluoroantimonate（Ag Sb F₆）（8mol%）,Potassium Acetate（0.2 equiv）,γ-Valerolactone as solvent,temperature 80 ^oC,Reaction 12 h.Under this reaction condition,most of the reactions can be carried out smoothly and the substrate compatibility is good.The expansion of electron-withdrawing and electron-donating groups on the substrate oxime has a relatively good substrate reaction yield,and1,3-diacetylene also shows good reactivity and regional selectivity.It is noteworthy that no additional oxidant is needed in the reaction process.In addition,GVL is extracted from lignocellulosic biomass and is a green solvent.Therefore,using GVL as the reaction medium instead of traditional organic solvents can reduce its environmental impact.（2）2-phenyl quinazoline-4（3H）-ketone as the substrate,Ethylene carbonate is a precursor compound of acetylene,The rhodium-catalyzed synthesis of C5,C6-unsubstituted isoquinoline[1,2-b]quinazolines was studied.The effects of different solvent catalyst additives and temperature on the yield of the reaction were investigated.The results show that the optimal reaction condition is:2-Phenylquinazoline-4（3H）-ketone（1 equiv）,vinyl carbonate（2equiv）,[Cp*Rh Cl₂]₂（2.5 mmol%）,Ag Sb F₆（10 mmol%）,GVL（2 m L）,130 ^oC,Reaction 24 h,Under the reaction conditions,most of the reaction can proceed smoothly and the substrate has good compatibility,and when the substrate 2-phenyl quinazoline-4（3H）-ketone are strong electron-withdrawing groups,such as nitro,The reaction can’t go on.The reaction process does not need to add additional oxidant,and the reaction is successfully achieved in the green solventγ-valerolactone,which makes the reaction more green.In addition,the comparative experimental results provide some evidence for the possible reaction pathways.