Studies On Transition-metal Mediated Cyanation Reactions

Aryl nitriles are versatile intermediates in organic synthesis because they could be easily transferred into various valuable functional groups, such as carboxylic acids, amidines, and amines, or converted into heterocycles, such as pyrazoles, triazoles, and tetrazoles. In this dissertation, the research background of transition-metal-mediated cyanation reactions has been reviewed, and the details of my study are summarized as following:1) Cu-mediated cyanation of aryl iodides and bromidesAryl nitriles were prepared through Cu(NO3)2·3H2O-mediated cyanation of aryl iodides and bromides using DMF as a single surrogate of cyanide. Moreover, this protocol could be scalable and practiced with benign operation. (Chapter 2)2) Cu-mediated cyanation of indoles and electron-rich arenesThe copper-mediated cyanation of indoles with DMF as a single surrogate has been realized. This approach could be applied for the cyanation of some electron-rich arenes and aryl aldehydes as well. Aryl aldehydes were demonstrated to be the key intermediates in the cascade process of cyanation of indoles and electron-rich arenes. (Chapter 3)3) Cu-mediated synthesis of 3-cyanoindolesWe developed a convenient method for the synthesis of 3-cyanoindoles from indoles using benzyl cyanide as cyanation reagent. The cascade reaction involves a copper-catalyzed aerobic C-H oxidation, a C-CN bond cleavage, and a copper-catalyzed aerobic oxidative C-H functionalization without directing group. The cyanation reagent is environmentally benign and the reaction is palladium-free and ligand-free. (Chapter 4)4) Cu-catalyzed preparation of 2-aryl-3-cyanobenzofuransCopper-catalyzed cascade synthesis of 2-aryl-3-cyanobenzofurans from o-hydroxybenzaldehydes and arylacetonitriles in the presence of copper acetate and sodium methoxide is reported. Many substituents tolerate the reaction conditions andproduce 2-aryl-3-cyanobenzofurans in moderate to good yields. The synthesized 2-aryl-3-cyanobenzofurans emit bright blue under UV light with a quantum yield up to 88.9%.(Chapter 5)5) Fe-mediated oxidative cyanation of tertiary aminesAn iron-mediated oxidative cyanation of tertiary amines with benzoyl cyanide and molecular oxygen or TBHP has been achieved. This reaction furnished a-cyanated tertiary amines under mild reaction conditions in good to excellent yields (up to 94%) with great diversity (19 examples). The reaction proceeded in a cascade way, including an iron-catalyzed oxidation of tertiary aminc to iminium ions and trapping them by cyanide anion. Our protocol features safety cyanation reagent, acid-free conditions,inexpensive iron catalyst, and aerobic oxidation. (Chapter 6)...