Studies On The Indoline C₇-H Bond Functionalizations Through Transition-metal Catalysis

In recent years,transition-metal-catalyzed direct C-H bond activations have evolved as an important tool for the efficient constructions of C-C and C-heteroatom bonds,and have played an important role in pharmaceutical chemistry and in the synthesis of biomedical materials and natural products.Along with the studies during the past decates,more and more catalytic systems as well as versatile directing groups have been succesfully expored,which greatly enrich the research field of the direct C-H bond functionalizations.Baesd on literature studies,pharmaceutical compounds in approximately 70%ratio contain heterocyclics,of which more than 10,000 are bioactive indole and indoline derivatives.Of the indole and indoline compounds,more than 200 substances have been identified as drugs or in clinical trials.Thus,the development of new protocols for the synthesis and/or modification of indole and indoline compounds is of great significance.In view of the physiological and pharmacological activities of indole and indoline compounds and based on the research progress in our group,this thesis mainly studies the transition-matal-catalyzed C-H bond activations on indoline compounds through the "directing group" strategy.Herein,the C7-functionalizations on indoline derivatives and the correcponding reagents have been succesfully explored through screenings of the catalytic systems as well as the suitable directing groups.The specific research contents are as follows:1)We have developed an effective strategy to achieve indoline C7-H bond construction and directly obtain a series of diarylamine derivatives with indoline and nitrosobenzene by using[Cp*Rh(MeCN)3][SbF6]2 as catalyst and pyrimidine as the directing group.Compared with the conventional C-N bond constructions,this method uses the readily available nitrosobenzene as the nitrogen source and provides mild,simple,low-cost and environmentally friendly C-N bond construction pathways(Scheme 1).Scheme 1 Synthesis of 7-aninoindoline compounds using nitrosobenzene as nitrogen source2)We have developed a Rhodium-catalyzed activation of indoline C6-H/C7-H bond with indoline and diphenylacetylene by using pyrimidine as a directing group.The functional groups were well tolerated and the substrate were widely applicable under the catalytic system,and good regioselectivity is still obtained for the unsymmetric alkenes as well as symmetric alkenes.Scheme 2 Dual C6-H/C7-H bond oxidation annulations of of indolines and internal alkenes.