코발트 촉매 하의 그리냐드 시약 형성을 통한 불소화 방향족의 탄소–불소 결합 기능화

Abstract

DoctorFluorine is the most electronegative element and is widely applied in various fields such as materials, polymers, catalysts, agrochemicals, or pharmaceuticals due to its unique physical and chemical properties. In particular, when fluorine is introduced into pharmaceutical candidates, it can generally increase metabolic stability and membrane permeability, resulting in higher drug activity, and 18F-fluorination can contribute to clarifying the metabolic processes of the drugsthrough positron emission tomography (PET) technology. With the increasing importance of the fluorine atom in many fields, diverse fluorinating reagents and methods have been developed to date. The fluorination reactions may be considered more important than the defluorination reactions due to the unique properties of fluorine, but the defluorination reactions also have a great advantage in organic synthesis. Since C−F bonds are one of the strongest bonds in general organic molecules, they are stable in most organic reactions, such as C−H bond or C−X bond functionalization (X=Cl, Br, I). Thus, C−F bond functionalization can be applied to late-stage functionalization (LSF), an attractive strategy for synthesizing complex organic molecules. The detailed properties of fluorine and an overall preliminary study of the defluorination reactions will be introduced in the first chapter. In the second chapter, cobalt-catalyzed C−F bond borylation of aryl fluorides will be described. Boronic esters can be used as a building block for various organic reactions, and organoboron compounds have the advantage of good stability and easy handling. In this study, the competitive aryl C−H bonds were not affected, and the reaction could proceed under milder reaction conditions than the previously reported defluoroborylation reactions. A simple mechanism study was also carried out, and two-step 18F-fluorination was achieved for expanding the scope of 18F-positron emission tomography probes. In the third chapter, cobalt-catalyzed C−F bond silylation of aryl fluorides via Grignard reagent formation will be discussed. Organosilanes are widely applied in various fields, such as organic electronics, photonics, pharmaceuticals, and polymers. This chapter describes selective defluorosilylation of the cobalt catalyst with a variety of inexpensive silicon sources. Further mechanism study was achieved and it supports in situ generation of Grignard reagent as a reaction intermediate. The reaction intermediate could be used in other organic synthesis reactions, such as phosphorylation or Kumada coupling reaction. In addition, defluorosilylated products could be converted into valuable building blocks