The Construction Of C-C/C-S Bond Via C-H Functionalization And Its Application To Cumarin And Flavone Derivatives Synthesis

In recent years, due to the deterioration of the ecological environment and strict policy of environment protection, it is urgent for organic chemists to find alternative sustainable methods to build organic compounds through selective functionalization of unreactive C-H bonds. Therefore, the construction of C-C and/or C-heteroatom bonds through C-H functionalization has attracted great attention recently owing to its high atom economy and high reaction efficiency.Coumarin and flavonoid derivatives are widely found in nature and are a significant class of natural products because of their remarkable spectrum of biological activities, which has aroused extensive attention among researchers domestically and abroad. According to statistics, by the end of 2003, the total number of flavonoids is more than 9000, and about more than 1200 kinds of coumarin have been isolated from nature. However, these vast numbers of natural products content in plants are limited, and difficult to obtain, in most cases, their bioactivity effectiveness is not high. Therefore, the methodology of coumarin and flavonoids structural modification and transformation is particularly important.Based on the exsiting literatures, as well as previous research work in our laboratory, in this thesis, we have synthesized many coumarin and flavonoid derivatives containing C-C and C-S bonds via C-H functionalization of the coumarin and flavonoids as the starting material. This paper includes the following sections:(1) Copper-catalyzed cross-coupling of flavones with ethersWe have developed a regioselective and atom economical cross dehydrogenation couplings of ethers with flavones by using CuO as a catalyst and TBHP as an oxidant via C(sp3)-H functionalization. All major products were isolated and analyzed in each reaction, which was the coupling of ethers to the electron-deficient β-position of the flavones ketone function. These reactions proceeded well via radical mechanisms and provided the corresponding ether-substituted flavone derivatives in good yields. These compounds have been characterized and verified by NMR, HRMS, FTIR and other characterization methods.(2) Iron-catalyzed methylation of coumarin derivativesHerein, we have developed a new coupling reaction in which coumarins and di-tert-butyl peroxide(DTBP) were used in the presence of inexpensive iron catalysts. This reaction proceed through a C(sp2)-H functionalization process to regioselectivity generate methyl-substituted coumarin derivatives in moderate to good yields. This coupling reaction will enrich current coumarin chemistry. These compounds have been characterized and verified by NMR, HRMS, IR and other characterization methods.(3) Ammonium iodide induced C-S bond-forming reactionHerein,different flavones with potential bioactivity were used as the starting materials, ammonium iodide was used to induce sulfenylation between flavones with various sulfenylating sources such as thiols, sulfonyl chlorides, disulfides, and sulfonyl hydrazides to generate C(sp2)-S bond were developed, and a series of corresponding flavones derivatives were obtained in good yields. This protocol features high efficiency, wide functional group tolerance, regioselective and atom economy. These compounds have been characterized and verified by NMR, HRMS, IR and other characterization methods.