Research On CO-Involved Palladium-Catalyzed Oxidative Carbonylations

Transition metal-catalyzed carbonylation reactions have developed into a powerful and straightforward method for the synthesis of carbonyl compounds. Carbon monoxide(CO) as versatile and readily available C1 building block has been widely used in academic laboratories and industry. Since the first application of carbonylation reactions in 1938, organic chemists have achieved impressive progress in this area. From the point view of green chemistry and energy-saving, despite all these achievements and significant discoveries, more efficient, green, and atom- and step-economical protocol to access important and novel molecule skeleton remains highly desirable. In this thesis, the development and applications of carbonylation reactions were first discribled briefly. The transition metal-catalyzed oxidative carbonylation reactions were highlighted in the thesis. The main part described the synthesis of polycyclic aromatic hydrocarbons(PAHs), N-substituted phthalimides and 1, 3, 4-oxadiazole-2(3H)-ones. The research contents are as follows:(1) A palladium-catalyzed oxidative carbonylation reaction for the synthesis of polycyclic aromatic hydrocarbons(PAHs) using CO as carbonyl source was developed. PAHs are important skeleton in pharmaceutical chemistry and materials science which have attracted significant attention from the academic and industrial communities. However, tranditional methods for the synthesis of PAHs usually show tedious s ynthetic procedures with low atom-efficiency using CO as C1 building block. Under our reaction system of Pd2(dba)3/Cu(OAc)2/TsOH, we successfully synthesized a series of PAHs. Furthermore, the direct oxidative coupling reaction under the absence of CO was also developed, and various derivatives could be constructed. This transformation provides a convenient and efficient protocol toward the synthesis of different PAHs.(2) An efficient method for the synthesis of N-substituted phthalimides with high atomand step-economy was reported. In our strategy, imine and H2 O, which serve as self-sufficient directing group and nucleophile, are all generated in-situ from the condensation of aldehyde and amine. This reaction starts from simple materials and provides a r apid access to phthalimides via palladium-catalyzed oxidative carbonylation in a one-pot manner. Various medicinally and biologically active compounds containing the core of phthalimides were successfully constructed under the reaction conditions.(3) A palladium-catalyzed oxidative O-H/N-H carbonylation of hydrazides for the synthesis of 1,3,4-oxadiazole-2(3H)-ones using CO as carbonyl source was developed. This method provides an efficient pathway for the synthesis of 1,3,4-oxadiazole-2(3H)-ones employing Pd(TFA)2 as catalyst and CuO as oxidant. This novel palladium-catalyzed carbonylation procedure has a broad substrates scope and good functional- group tolerance under mild conditions. Importantly, it provides a novel and straightforward access to the synthesis of BMS-191011 which is a popular skeleton in pharmalogical and biological field.