Tandem Cyclization Reaction Based On Cross-dehydrogenation Coupling

Direct cross-dehydrogenative-coupling (CDC) reactions, which combine two C-H bonds to form new C-C bonds avoiding the requirement for preparing pre-functionalized reagents, have emerged as powerful and environmentally friendly alternatives in organic syntheses. It can provide a step and atom-economical strategy for the synthesis of complex molecules from simple materials via C-H functionalization. Although many efforts have been made to develop CDC methodologies to access useful motifs, there are still some major challenges that need to be addressed in this field.Cyclic compound is one kind of important organic compounds. Many drugs, natural products, and synthetic intermediates with important biological activity contain cyclic motifs. For example, isoindolinones are present in many natural products, and they exhibit significant pharmacological activities.Traditionally, these cyclic compounds are primarily synthesized via a multi-step reaction or intermolecular cyclization. These methods have some shortcomings: uncommercially available starting material, harsh reaction conditions, low atomic utilization, massive wasting emissions. The limited tolerance of environment on pollution forces humans to develop green high efficient and emission free technology. The concept of green chemistry is put forward in this background. Therefore, in the development of cyclic compounds, exploring high efficient routes to realize cyclization reaction is a significant research field, which will play an important role both in the production of green chemicals and in the protection of environment.Based on these, this thesis mainly focuses on the following aspects.In the first chapter, the development of CDC reactions catalyzed by transition-metal is reviewedIn the second chapter, a three-component tandem CDC cyclization via a Pummerer type rearrangement to afford biologically relevant isoindolinones from aromatic acid, amides and DMSO, was described. This intermolecular tandem reaction undergoes Csp2-H/Csp~3-H cross-dehydrogenative-coupling, C-N bond formation and an intramolecular amidation. Notable feature of this novel protocol is avoiding catalyst and additive apart from oxidant.In the third chapter, a Rh-catalyzed direct oxidative cross coupling reaction of aromatic acid was developed. It offers a straightforward and atom-economical protocol for the synthesis of conjugated 4,8-dimethyl diphenic anhydride in acceptable good yields. In the reaction, the silver carbonate was used as oxidant and copper(II) chloride dihydrate was used as additive. The establishment of this method provides a simple and convenient route for the synthesis of the diphenic anhydride compounds.In the fourth chapter, the whole work and innovation of this thesis are summarized.