Development of New Catalytic Reactions for Efficient Syntheses of Two Versatile Building Blocks: Cyclic Imides and Biaryls

Abstract

Chemical processes to afford complex molecules usually require laborious multi-step synthesis, accompanied by toxic waste generation. The development of efficient synthetic methods that can replace conventional procedures have gained increasing interest in organic chemistry. Catalytic reactions involving organometallic catalysts can provide an atom-economical and streamlined process. This thesis addresses the development of novel catalytic reactions that enable the conversion from simple feedstock molecules to value-added chemicals. <br/> Chapter 1 includes an introduction to amide synthesis via alcohol activation. Dehydrogenative amide synthesis using alcohols and amines as substrates offers an environmentally benign and efficient protocol, alternative to conventional amide synthesis. The principle of alcohol dehydrogenation can also be applied to the preparation of N-heterocycles. Chapter 2 describes synthesis of cyclic imides from alcohol and nitrile starting materials. The developed method provides an atom-economical and easily accessible method for forming cyclic imides from simple and versatile starting materials. Further mechanistic studies demonstrated that this reaction involves hydrogen transfer as a substrate-activating strategy to generate both reactive nucleophiles and electrophiles in the reaction mixture.<br/> In Chapter 3, the direct C–H arylation of arenes is reviewed including the current state of the art as well as the background and basics of C–H activation chemistry. Direct arylation of arenes can provide an alternative approach to the syntheses of biaryls, which are conventionally produced by traditional cross-coupling reactions. Chapter 4 describes development of a Pd–diimine catalyst for direct CH arylation of simple arenes without directing or activating groups. A diimine-assisted Pd catalyst exhibited the highest turnover number (TON) reported to date in the CH arylation of benzene. It also showed superior efficiency with a small number of equivalents of arene substrates, whereas all previous examples required excess arenes. Mechanistic investigations including a kinetic study, identification of reaction intermediates, and stoichiometric reactions provided solid evidence of a cooperative bimetallic mechanism.<br/>