Carbonylation Reactions Involving CO Gas

Organic synthesis via transition-metal catalysis is the frontier area of chemistry research, among which the carbonylation reaction is one of the most efficient methods to construct carbonyl compounds. Early in1930s, transition-metal catalyzed organic reactions involving CO (eg. hydroformylation reaction) have been discovered and widely utilized in industry. Since the report by Heck and coworkers in1974, transition-metal catalyzed carbonylation reactions have undergone rapid development. Meanwhile, radical carbonylation reactions have also attracted increasing attentions among organic chemists. However, owing to the concept of green chemistry, the development of novel, green and efficient carbonylation reactions is highly desirable. This thesis firstly summarized the development of carbonylation reactions especially oxidative carbonylation and radical carbonylation. Then this thesis described the oxidative alkoxycarbonylation of heteroarenes, the double C-H carbonylation of diaryl ethers and the radical alkoxycarbonylation of aryl halides. The detailed contents are as follows:1. The first Pd-catalyzed aerobic C-H carbonylation of heteroarenes and alcohols to form esters under base-free conditions was developed. Various reaction parameters were screened and PdCl2(PPh3)2as catalyst and Cu(OAc)2as co-oxidant gave the best results under balloon pressure of CO. Direct oxidative carbonylation of various heteroarenes including indole, thiophene and benzothiophene with different alcohols was achieved in good to high yields. The reaction showed remarkably high regioselectivity and presented an environmentally benign protocol for the synthesis of heteroaryl carboxylic acid derivatives. Unprotected indoles occurred oxidative N-H carbonylation under the same reaction conditions.2. The first oxidative double C-H functionalization/carbonylation of diaryl ethers was developed. Various reaction parameters were screened and the catalytic system consisting of Pd(OAc)2, K2S2O8and TFA gave the best results. A variety of diaryl ethers bearing different functional groups were tested under the optimized conditions affording xanthones in good to excellent yields. Preliminary mechanism studies with the help of React IR were also conducted revealing that the second C-H functionalization step might be the rate-determining step. This transformation provides an effective and practical protocol towards the synthesis of xanthone structure that forms the central core of a variety of naturally occurring and manmade organic compounds.3. The first transition-metal-free alkoxycarbonylation of aryl halides was achieved in the presence of1,10-phenanthroline and KO’Bu. Various aryl and heteroaryl iodides were tested in this catalytic system giving satisfactory to good yields. A variety of functional groups were tolerated under the optimal reaction conditions. This transformation provides an effective and practical protocol towards the syntheses of aromatic esters avoiding the usage of noble metal catalysts. Preliminary mechanism studies including the radical trapping experiments and EPR experiments indicated the participation of radical intermediate. A radical chain mechanism was proposed.