Role Of Various Directing Groups In The Field Of C-H Activation

Site selective C-H bond functionalization has become an effective tool to construct a variety of active molecules.With the development of this field,researchers found that the coordination ability of directing group with transition metals could significantly enhance the activity of C-H bond functionalization.At present,various directing groups have been used in site selective C-H bond functionalization,including carboxyl,aldehyde,imine,amide,amino and nitroso groups.Therefore,it will be a challenging and valuable topic to explore the application value of directing groups in the field of transition metal catalyzed C-H activation and the development of C-H functionalization to synthesize complex molecules.In the first chapter,we mainly summarize the directing group strategies,which are divided into（1）irremovable directing group strategies;（2）removable directing groupstrategies;（3）traceless directing group strategies.Various heteroatom directing groups have been designed and successfully applied to the ortho and meta functionalization of aromatic C-H bonds（including arylation,alkylation,alkenylation,alkynylation,amination and halogenation）,and a series of valuable active molecules have been constructed.This provides a convenient way for the preparation of drug molecules or materials.In the second chapter,we developed a novel method for the synthesis of 3H indole derivatives by using the strategy of irremovable directing group.With the assistance of imine directing group,rhodium catalyzed N-phenylbenzamidine and pyridine triazole compounds were activated/cyclization/deaminatation to form a 3H-indole ring.The imines in benzamidine could not only coordinate with metals,but also cyclize with alkylation products in situ.The reaction was compatible with different functional groups,and various 3H-indole derivatives containing C3quaternary center and pyridine group are simply synthesized.The mechanism of this method is also understood through mechanism experiments such as deuterium experiment and kinetic isotope experiment,and a reasonable catalytic cycle is described.In the third chapter,we developed an efficient method for the synthesis of biaryl-2-nitriles by using the traceless directing strategy.In the presence of iminoethyl directing group,the new C-C bonds formed between phenyliminoethyl and heteroaromatics via double C-H activation.In this strategy,the first step is coordination with metal to complete the activation of C-H bond.After the completion of the reaction,ethanol is spontaneously removed and converted to cyano group.The obtained biaryl-2-nitriles were further converted into oxygen heterofused rings and other useful compounds.This also proves the practicability of the strategy.By means of intermediate monitoring and deuterization experiments,we determined that the bis（aryl）-2-iminoethyl ester was a possible intermediate,and speculated the reasonable Rh（Ⅲ）-Rh（IV）-Rh（II）-Rh（Ⅲ）catalytic cycle.In the fourth chapter,we developed first iridium catalyzed C-H activation/cyclization of NH sulfonimides with N-alkoxybenzamide by using the immovable directing group strategy.Readily available N-alkoxybenzamide is used as amination reagent and sulfonimide as bifunctional directing group.It could not only locate C-H activation site,but also condense with amide to form six membered heterocycle.A series of thiadiazine 1-oxides were prepared in moderate to good yields.Through a series of mechanism studies,we determined the active intermediates and proposed a reasonable catalytic cycle.In the fifth chapter,we used N-methoxybenzamide as amination reagent to realize Rh（Ⅲ）-catalyzed C-H activation/amidation/cyclization.Imine is an irremovable directing group in this reaction.It forms quinazoline ring by intramolecular condensation with amide after assisting ortho C-H amination.Resulted quinazoline products could be transformed into other useful molecules.The mechanism of the[4+2]reaction was further understood by intramolecular competition experiment,deuterium experiment and KIE results etc.In the sixth chapter,we developed the remote C-H bond alkylation of mono phosphine compounds by ustlizing a cheap ruthenium catalyst.On the one hand,phosphorus atom could coordinate with ruthenium to activate C-H bond.On the other hand,it remains in the product.Therefore,this is an efficient way to prepare novel phosphine ligands.A various of phosphine compound were modified in good yields with good functional group compatibility.Preliminary mechanistic studies indicated that a P^Ⅲ-assisted ortho-cyclometalation/remoteσ-activation pathway might be involved in this methodology.In the future,we will explore the feasibility of other selective remote C-H functionalization using phosphine as directing groups.