Transition-metal Catalyzed C-F And C-H Bond Activation

The inert C-F bonds activation has emerged as one of the hottest challenging research topics in organic chemistry in recent years. The C-F bond is the strongest single bond to carbon. Research on C-F bond activation will help to gain deep understanding on the nature of this inert bond, and will be of great importance in degradation of fluoroaromatics waste. The most important point is to provide new methods to synthesize fluoroaromatics. Nickel-catalyzed C-F bond activation has been well-developed in recent years. Howerver, there are still a lot of limitations in the catalytic reactions. Development of new nickel-catalyzed C-F bond activation/functionalization of polyfluorinated arene is still a great demand. C-H bond activation is one of the most attractive research topics and has made great progress in decades. However, it is still a significant challenge to develop selective and mild methods. Herein, the nickel-catalyzed C-F bond borylation, C-F bond involved Suzuki-Miyaura cross-coupling reactions, the stoichiometric reactions of nickel with polyfluorinated arenes and nickel-catalyzed catalytic hydrodefluorination reactions are investigated. Besides, synthesis of dibenzofurans, xanthones and 6H-benzo[c]chromenes by palladium-catalyzed tandem denitrification/(Carbonylation) and C–H activation based on diazonium salts are explored. This thesis includes six parts as below. 1. IntroductionThis chapter consists of four sections. Section 1 is a minireview on transition-metal catalyzed C-F bond borylation. Section 2 focuses on fluoroaromatics involved Suzuki-Miyaura cross-coupling reactions. Section 3 emphasizes on nickel-catalyzed C-X bond activation in stoichiometric reactions. Section 4 summarizes palladium-catalyzed C-C cross-coupling reactions of aryl diazonium salts. The content, purpose and meaning of my research topics are also introduced in this chapter. 2. NHC Nickel-Catalyzed Selective Borylation of Polyfluoroarenes via C-F Bond CleavageArylboronic esters are quite versatile reagents for cross-coupling reactions in construction of C-C bonds and functional group interconversion to C-X bonds, representing significant intermediates in organic synthesis. Fluoroaromatics play an important role in pharmaceuticals, agrochemicals and materials, and there has been a lot of research currently aimed at the development of new ways to introduce fluorine or fluorinated building blocks into organic molecules. It would be an elaborate way to achieve this goal by employing fluoroaromatic boronate esters in cross coupling. Herein, the [Ni(IMes)2]-catalyzed transformation of fluoroarenes into arylboronic acid pinacol esters via C-F bond activation and transmetallation with bis(pinacolato)diboron(B2pin2) has been developed. In our protocol, several different solvents and additives were screened. Various partially fluorinated arenes with different moieties of fluorination could be converted into their corresponding boronate esters under our optimized conditions. The mechanism of this reaction was investigated. 3. NHC Nickel-Catalyzed Suzuki-Miyaura Cross Coupling Reaction of Arylboronate Esters and PerfluorobenzenesFluoroaromatics can be found in a lot of organic molecules, such as pharmaceuticals, agrochemicals, and materials. Therefore, Fluoroaromatics involved C-C cross-coupling reactions have been well-developed in recent years. Among them, Suzuki-Miyaura cross-coupling of poly- and perfluorinated arenes represents an attractive reaction due to the mild conditions employed and the compatibility with many potential functional groups. In this thesis, an efficient Suzuki-Miyaura cross coupling reaction of perfluorinated arenes with aryl boronate esters using NHC Nickel complexes as catalyst is described and the efficiency of different boronate esters(p-tolyl-Beg, p-tolyl-Bneop, p-tolyl-Bpin, p-tolyl-Bcat)(eg = ethyleneglycolato; neop = neopentylglycolato; pin = pinacolato, cat = catecholato) and the corresponding boronic acid(p-tolyl-B(OH)2) in this type of cross-coupling reaction with perfluorinated arenes was evaluated. 4.C-F and C-H Activation of Polyfluoroarenes at Nickel bearing a bulky NHC ligand and Application in Hydrodefluorination ReactionsThe stoichiometric reactions of [Ni(IMes)2] with different fluorinated arenes were investigated. These reactions are performed with a high chemo- and regioselectivity. The reactions of [Ni(IMes)2] with octafluorotoluene, hexafluorobenzene and 1,2,3,5-tetrafluorobenzene in toluene resulted in C-F oxidative addition to form trans-[Ni(IMes)2(F)(4-(CF3)C6F4)], trans-[Ni(IMes)2(F)(C6F5)] and trans-[Ni(IMes)2(F)(2,3,5-C6F3H2)], respectively. The 19F{1H}NMR spectrum featured the C-F activation adducts singlets from-350 to-365 for the nickel fluorides. Whereas in the case of 1,2,4,5-tetrafluorobenzene, a C-H activation trans-[Ni(IMes)2(H)(2,3,5,6-C6F4H)] was produced. In the 1H NMR spectrum, a multiplet peak was observed at δ-15 ppm for a nickel hydride complex. Meanwhile, [Ni(IMes)2] reacted with pentafluorobenzene to generate a major C-F bond activation trans-[Ni(IMes)2(F)(2,3,5,6-C6F4H)]. X-ray analysis further accounts for nickel(II) complexes Ni(IMes)2(F)(ArF) and [Ni(IMes)2(H)(2,3,5,6-C6F4H)], which confirms the results we have gathered so far. The catalytic hydrodefluorination reactions of octafluorotoluene, hexafluorobenzene, pentafluorobenzene using [Ni(IMes)2] as a catalyst and hydrosilane as a reducing reagent in toluene at 80 °C were investigated ending with high selectivity and yields. 5. Synthesis of Dibenzofurans and Xanthones by Palladium-Catalyzed Tandem Denitrification/(Carbonylation) and C–H Activation on Diazonium SaltsDibenzofurans are of great importance in organic synthesis, finding wide applications in medicine and some other chemicals. A palladium-catalyzed method for intramolecular cyclization of ortho-diazonium salts of diaryl ethers which are synthesized through 4 steps starting from phenols to give dibenzofurans in high yields is described. This method has several merits such as simplicity of operation and good tolerance to substrates. Xanthone skeleton exists in a lot of biological natural products, and is one of the important backbones of medicine precursors. Besides, a series of xanthones with different functional groups are formed in high yields through denitrogen/carbonylation and C–H activation reactions using ortho-diazonium salts of diaryl ethers as substrates under optimized conditions. 6. Synthesis of 6H-benzo[c]chromenes by Palladium-Catalyzed Tandem Denitrification and C–H Activation on Diazonium SaltsThe skeleton of 6H-benzo[c]chromenes is an important substructure can be found in natural products and bioactive compounds. A highly efficient palladium-catalysed phenyl diazonium tetrafluoroborate participation of C–H activation ring closure protocol has been developed. A series of 6H-benzo[c]chromenes have been synthesized by intramolecular cyclization of ortho-diazonium salts tetrafluoroborate of benzyloxyphenyl or phenoxymethyl phenyl. This transformation allows the synthesis of 6H-benzo[c]chromenes with a variety of functional groups from simple and easily accessible precursors. Considering that the methylene group in 6H-benzo[c]chromenes is easily to be oxidized, an efficient and eco-friendly oxidation method for the synthesis of benzo[c]chromen-6-ones from corresponding benzo[c]chromenes is explored. The reaction was conducted under a condition of TBHP/ KI /pyridine mixture.