Study On Rhodium-catalyzed Direct C-H Alkenylation Reaction Of Indole Derivatives

Indoles and indolines are very important active heterocyclic compounds,especially indoles and indolines with alkenyl groups,which have been widely used in the fields of fine chemicals,medicine,agricultural chemicals and functional materials.In recent decades,transition metal-catalyzed C—H bond activation reactions have developed rapidly and become one of the hottest research fields in organic chemistry due to its atom economy and step economy.Compared with traditional coupling reactions,transition metal-catalyzed C—H bond activation has such advantages including without substrate pre-activation,avoiding the use of expensive ligands,and reducing the excess metal waste.It has become an important tool in the synthesis of bioactive molecules and functional materials.In this thesis,the rhodium-catalyzed C—H alkenylation for the highly efficient synthesis of indoles and indolines with terminal vinyl groups were developed.These research contents are as follows:1.Rhodium-catalyzed direct C2—H alkenylation reaction of indoles with vinyltriethoxysilaneEmpolying commercially available vinyltriethoxysilane as the vinylating reagent,a highly efficient Rhodium-catalyzed direct C2—H alkenylation of indoles been developed.When the reaction was catalyzed by[Rh Cp*Cl₂]₂ with Cu（OAc）₂ as oxidant in the presence of Ag F in DCE（1,2-dichloroethane）at 90 ^oC,a series of terminal vinylindole derivatives could be obtained in 42%to 88%yields.The kinetic isotopic effect experiment was conducted and a K_H/K_D value of 5.7 was obtained,which suggested that the C—H bond cleavage was involved in the rate-determining step.The competition experiment between differently substituted indoles indicated that electron-rich indoles were preferentially converted,suggesting that an electrophilic C-H activation process might be involved in this transformation.A possible reaction mechanism,including coordination,C—H bond activation,transmetallization,reductive elimination and oxidantion,was then proposed.Moreover,this synthetic method was successfully applied to the synthesis ofδ-carboline derivative.2.Rhodium（III）-Catalyzed direct C7—H alkenylation reaction of indolines with alkenyl boratesUsing easily synthesized alkenyl borates as the alkenyl source,a new Rh（III）-catalyzed direct C7—H alkenylation of indolines with alkenyl borates was described.The optimal reaction conditions was established by the examination of directing groups,solvents,and temperature,including Me OH as solvent,Ag₂CO₃ as oxidant,the temperature of 60 ^oC,and the reaction time of 4 to 6 h.The present method features wide substrate scope,good functional group compatibility.Various indolines containing electron-donating groups or electron-withdrawing groups could participate in this transformation.Furthermore,electron-donating groups（e.g.,Me,t Bu,Ph）,fluorine-containing substituent（OCF₃）,and halogens（e.g.,F,Cl）of alkenyl borates were all tolerated in this reaction,and the highest yield is 95%.A possible mechanism was proposed,which includes:coordination,C—H bond activation,transmetallization,reductive elimination and oxidation.A gram-scale experiment for this C–H alkenylation reaction is successfully carried out with 1.0 mol%loading of catalyst,and the desired product is obtained without significant decrease.In addition,the alkenylated product can be easily transferred into the C7-terminal styryl indole derivative through the oxidation reaction in presence of Mn O₂.And then,the directing group could be also easily removed to give the N-free indole derivative in 90%yield.