The Study On Transition-Metal-Catalyzed Directed C-H Activation With Carbin Precursors

Carbin precursor compounds is a kind of easily available organic intermediates,which can efficiently construct C-H bonds or C-hetero bonds through migratory insertion mechanism of metal carbeen.With the development of directed C-H bond activation,transition-metal-catalyzed directed C-H bond activation cascade annulation with carbin precursors have emerged as powerful strategy for the construction of nitrogen heterocyclic skeleton compounds owning to its step economy and atomic economy.It's found that the nitrogen heterocyclic skeleton structure constructed by such transformation is not abundant enough hrough the review of domestic and foreign literatures.Given the important use of nitrogen heterocyclic skeleton molecules in the fields of medicine and organic photoelectric materials.In this study,carbin precursors were used as coupling reagents to construct nitrogen heterocyclic skeleton derivatives with novel structure and excellent biological activity through C-H activation cascade annulation.Some research work was carried out:(1)The rhodium(?)-catalyzed[4+2]annulation of 2-arylindole with dioxazolone was established.The optimized conditions were determined by screening the catalyst,additives,solvent and other factors.With the optimized conditions in hand,the suitability of 2-arylindole and dioxazolone substrates was investigated.The results showed that the reaction was suitable for the transformation involving different electronic and steric effect substrates,giving indolo[1,2-c]quinazolines compounds with good yield.A series of mechanism experiments deduced that the reaction underwent C-H bond activation,migratory insertion and nuclephilic cyclization in sequence.Bioactivity tests indicated that the synthesized target products had certain antitumor activity,and some compounds specifically had good inhibitory effect on human lung adenocarcinoma cells.This work realized the highly selective activation of aromatic C(sp2)-H assited by amino,and developed a new method for the synthesis of indolo[1,2-c]quinazolines compounds with dioxazolone as the coupling reagent.(2)The rhodium(?)-catalyzed C-H activation cascade[4+2]annulation of 2-arylquinazolinone with sulfoxonium ylides was developed.The best reaction conditions were established through the investigation of various factors that affect the reaction efficiency.Substrate expansion showed that the transformation had great substrate compatibility for 2-arylquinazolinone and sulfoxonium ylides.Thirty isoquinolino[1.2-b]quinazolinones compounds were constructed with good yield,which was in the range of 51-91%.Based on the investigation of the reaction mechanism,it was proposed that the reaction experienced series processes of C-H bond activation,migratory insertion,nuclephilic cyclization and aromatization.Bioactivity tests indicated that the compound 3-3af had a great antitumor activity against human lung adenocarcinoma cells.The compound 3-3an specifically showed better inhibitory effect on human breast cancer cells than positive control drugs.In this work,the[4+2]annulation of 2-arylquinazolinone with sulfoxonium ylides in the presence of acid-free addtives was realized,which provided a new idea for the preparation of isoquinolino[1.2-b]quinazolinones.(3)The cheap ruthenium-catalyzed[3+2]annulation of 1-naphthylamine with ?-carbonyl diazoester was achieved.The optimized condition were obtained through the investigation of catalyst,co-solvent and other factors.The suitability of substrates showed that 1-naphthylamine and diazo with different substituents could obtain the desired products with good yields.The synthesis of 2,2-disubstituted-extended 3-oxindoles derivatives can be achieved by the sequence of C-H bond activation,migratory insertion,nuclephilic cyclization and 1,2-migration.Bioactivity tests indicated that some of the compounds showed great antitumor activity,with IC50 between 20 and 40 ?M,which was the same level as or better than the positive control drugs.Even more interestinfly,these C-H activation products showed bright cyan fluorescence in aqueous solutions,which rendered them attractive for fluorescent imaging in living cells.In this work,ruthenium-catalyzed selective C-H activation of 1-naphthylamine assisted by the amino under the promotion of green solvent was realized.