Studies Of Transition-Metal-Catalyzed C-H Bond Activation For The Synthesis Of Nitrogen-Containing Compounds

Directing group-assisted transition-metal catalyzed C-H activation reaction has emerged as one of the most important and powerful tool for the construction of C-C and C-X bonds owing to its atom-and step-economic manner.Nitrogen-containing compounds have found wide application in the filed of medicine,agriculture,functional materials,which serve as the core framwork of many medicines,natural products and organic functional molecules.Therefore,it is of great significance to study the synthesis of nitrogen-containing compounds.Traditionally,the transition metal-catalyzed cross couplings,such as Ullmann-Goldberg,Buchwald-Hartwig and Chan-Lam aminations,have been proven to be the practical methods for the synthesis of diverse nitrogen-containing compounds.However,the pre-functionalization of the substrates is inevitable in these transformations,which also gives rise to the formation of undesirable toxic waste.Hence,the development of transition metal catalyzed C-H bond activation reaction for the synthesis of nitrogen-containing compounds has more profound theoretical and practical significance.This manuscript mainly focused on the directing group-assisted transition metal-catalyzed aromatic C(sp2)-H functionalization for the synthesis of nitrogen-containing compounds.The contents were listed as follows:1.Nickel-catalyzed direct amination of arenes with alkylaminesThe direct cross-dehydrogenative coupling between arenes and simple amines represents an ideal and environmentally attractive strategy.We disclosed nickel-catalyzed direct amination of arenes with alkylamines with the assistant of 8-aminoquinoly auxiliary.The transformation exhibited broad substrate scope and a variety of functional groups could be well tolerated.Notably,the good regioselectivity was observed and the monoaminated product was solely obtained in the reaction,without the formation of di-aminated product.The intermolecular kinetic isotopic effect studies demonstrated that the C(sp2)-H cleavage of benzamides might be involved in the rate-determining step.The radical capture experiment implicated that a single electron transfer(SET)process might be involved in the reaction.2.Cobalt-catalyzed direct amination of arenes with alkylaminesUntil recently,the majority of transition-metal catalyzed C-H functionalization were achieved employing precious second-and third-row transition metals.Therefore,the development of cheap-metal-catalyzed C-H bond activation is important.Cobalt is earth-abundant,easily available,and inexpensive.Due to the lack of studies on its catalytic activity,the example of cobalt catalyzed C-H bond activation is scarce.We herein developed a new method for the synthesis of arylamines via cobalt-catalyzed direct C-H amination with simple secondary amines.The transformation exhibited broad substrate scope and provided the straightforward protocol for the synthesis of arylamines.A range of carboxamides bearing electron-rich and electron-deficient groups were subjected to the standard conditions and the corresponding aminated products could be obtained in moderate yields,which also displayed the high functional group tolerance.In addition,a wide range of 6-membered cyclic secondary amines bearing various functional groups were compatible with the reaction conditions.Differnent from nickel-catalyzed C-H amination,the preliminary results indicated that the C-H cleavage of benzamide was presumably not involved in the rate-determining step.3.Cobalt-catalyzed synthesis of quinolines from the redox-neutral annulation of anilides and alkynesAfter studying the cobalt-catalyzed C-N bond construction reaction,we explored the reaction of cobalt catalyzed C-H activation for the synthesis of quinoline compounds.Herein,we investigated the cobalt-catalyzed annulation of anilides with internal alkynes for the rapid synthesis of quinolines.It was found that the knowledge that Lewis acids improve the electrophilicity of amides permitted the significant improvement of the annulation by the use of Zn(OTf)2,which may play a significant role in increasing the electrophilicity of ketones via coordination.Furthermore,the C-M bond of the alkenyl-CoⅢ species could be more polarized than that of the RhⅢspecies and be more nucleophilic to react with a less electrophilic group,which demonstrated that the catalytic effect of Cp*Co(III)was better than that of Cp*Rh(III).Notable features of the transformation included high efficiency,broad substrate scope and good functional group tolerance.The preliminary results indicated that the C-H actication was presumably involved in the rate-determining step.A key intermediate was observed by the MALDI-TOF-MS analysis experiment,which partially supports the proposed mechanism.4.Ruthenium-catalyzed ring-opening addition of anilides to 7-azabenzonorbomadienes:a diastereoselective route to hydronaphthylaminesHydronaphthylamines are ubiquitous structural motifs that widely exist in natural products,pharmaceuticals and biologically active molecules.Herein,we disclosed a ruthenium-catalyzed ring-opening reaction for the assembly of valuable hydronaphthylamines from anilides and 7-azabenzonornadiene.The reaction proceeded efficiently under redox-neutral conditions and displayed good functional group compatibility.Notably,the transformation exhibited high stereoselectivity to afford cis-configuration products.7-Oxabenzonorbornadienes were compatible with the catalytic system to give functionalized naphthalenes under the modified reaction conditions.The intermolecular kinetic isotopic effect studies demonstrated that the C(sp2)-H cleavage might be involved in the rate-determining step.The intermolecular competition experiment suggested that the C-H activation probably occurs via a concerted metalation-deprotonation mechanism.