Transition Metal-free C2/C3-position Cycloaddition And Cross-dehydrogenation-coupling Reaction Of Indoles

Indoles belong to a kind of important organic compounds with unique properties,which have been widely used in organic synthesis,biology,pesticide,medicine,and dyestuff due to their biological activity.In recent years,considerable efforts have been made on the functionalization of indoles,providing versatile methods for the synthesis of indole derivatives.However,some issues such as the use of transition metal,tocxic oxidants,and critical reaction conditions extremely hinder their synthesis and late-stage applications.The development of mild and efficient green synthesis methods for the functionalization of indoles is still a big challenge.In this thesis,the strategy of aryne insertion and electrochemistry are used to explore the selective functionalization reactions of indole,including the C2and/or C3-position C–H bonds,respectively.(1)The[5+2]and[2+2]cycloaddition reactions of 1H-indole and 2-(trimethyl-methyl silyl)phenyl trifluoromethanesulfonate are systematically explored with cesium fluoride as a base,18-crown-6 as an additive,and acetonitrile as a reaction medium,which can enable the efficient construction of benzazepine skeletons.Particularly,the de-aromatization reaction of indoles can readily proceed at room temperature without the use of any transition metal catalyst,affording a series of dibenzo[b,e]azepine derivatives in moderate to good yields.Increasing the hindrance at the C2-position of 1H-indoles allows the[2+2]cyclization reaction to give a series of benzocyclobutane indoline derivatives.In addition,the mechanistic experiments confirm that the reaction of 1H-indoles with arynes first undergo a[2+2]cycloaddition,followed by a[5+2]cycloaddition reaction via ring expansion to give the according products.(2)The method of electrochemcial synthesis has been used to investigate the cross-dehydrogenation-coupling reaction of indoles and the benzyl C–H bond of xanthene in the absence of any transition metal catalyst and external oxidant.It is found that the electrochemical cross-dehydrogenation coupling reaction can proceed smoothly at room temperature with ⁿBu₄NPF₆ as the electrolyte,carbon rod as the positive electrode,platinum sheet as the negative electrode,5 m A current,and acetonitrile and methanol as the mixed solvents,which afford a variety of 3-Alkyl-indole in moderate to good yields.Mechanistic experiments,CV experiments,and control experiments support that a possible radical pathway is presumably involved in this CDC reaction.