Studies On The C-H Bond Activation And Cvclization Reactions Involving Ketenimines

Ketenimines have been demonstrated as an important and versatile synthesis intermediate in organic synthesis.They have been widely applied in the synthesis of heterocyclic compounds and total synthesis of natural products.In this thesis,various preparation methods of ketenimines and different types of reaction ketenimines involved have been comprehensively reviewed.On the basis,we have developed some new reactions of ketenimines involved in C-H bond activation and/or cyclization.The details are summarized as following:(1)We have developed a rhodium-catalyzed C-H activation/annulation of ketenimines with N-methoxybenzamides.Two types of annulations have been revealed based on the structure variation of N-methoxybenzamides.Thus,3-aminoisoindolin-1-ones and 3-(diarylmethylene)isoindolin-1-ones were constructed through[4+1]and[3+2]annulation manners,respectively.The afforded[4+1]products could further convert to other kinds of compounds.Possible mechanism for the selective formation of[4+2]and[3+2]annulations products was proposed on the basis of experimental computational results,which was mainly controlled by the ortho-substituent steric hinderance of N-methoxybenzamide.(2)We have further studied the rhodium-catalyzed C-H activation/annulations of various ketenimines with N-methoxybenzamides.The reaction outcomes were found to be dependent on the molecular structure of the ketenimine component.The β-alkyl substituted ketenimines furnished 3-iminoisoquinolin-1(2H)-ones through a formal[4+2]annulation manner,while the β-ester group substituted ketenimines afforded 3-aminoisoindolin-1-ones through a formal[4+1]annulation manner.Possible mechanism for the selective formation of[4+2]and[4+1]annulations products was proposed on the basis of experimental and computational results.Furthermore,the synthesized[4+2]products could undergo an intramolecular Cu-catalyzed C-N coupling to be converted to benzo[4,5]imidazo[1,2-b]isoquinolin-11-ones,which could be directly prepared from ketenimines and N-methoxybenzamides by a one-pot Rh-catalyzed annulation/Cu-catalyzed C-N coupling sequence.The resulted heterocyclic products are an important in medicinal chemistry.(3)We have demonstrated that ketenimines could be used as the coupling partner in Co(Ⅲ)-catalyzed cross-coupling reactions through the othro C-H activation of some pyrimidinyl substituted arenes.The Co-catalyzed reaction of 1-(pyrimidin-2-yl)indoles and ketenimines furnished 2-enaminylated indoles in moderate to excellent yields.And the substrate scope could be further extented to 1-(pyrimidin-2-yl)pyrroles,1-(pyrimidin-2-yl)indolines and 2-phenylprimidines.The substrates are readily available.Moreover,the synthesized indole derivatives could be conveniently converted into 3H-pyrrolo[1,2-a]indol-3-ones,which are an important class of heterocyclic compounds in medicinal chemistry.(4)We have also demonstrated that ketenimines could be used as the coupling partner in Mn-catalyzed cross-coupling reactions through the othro C-H activation of 1-(pyrimidin-2-yl)indoles.It could afford 2-enaminylated indoles by merely using Mn2(CO)10 as the catalyst.Beside β-ester group substituted ketenimines,acid-sensitive triaryl-substituted ketenimines were also suited for this reaction,during which pyrimidinyl group migration was occurred.Besides,the afforded products could further convert to benzo[c]carbazoles.(5)We developed an efficient and feasible method to prepare 5-formyl-1,2-disubtituted imidazoles from readily available propargylic amines and ketenimines.The cascade reaction was promoted by iodine and used oxygen as oxidant.The reaction could also work under AgOTf-catalyzed condition and afforded 1,2,5-trisubstituted imidazoles.The iodine promoted reaction involved nucleophilic addition/iodine-catalyzed electrophilic cyclization/tautomerism/oxidation cascade afforded the products in moderate to good yields with a wide substrates scope.