Redox Activation of C–C and C–H Bonds Using Visible Light.

[摘要] Carbon-carbon and carbon-hydrogen bonds constitute essential components of organic frameworks and impart significant amounts of chemical inertness and stability to complex architectures. These bond types are common, and the ability to modify or selectively cleave these bonds in the presence of other sensitive functional groups is a worthy goal of synthetic chemistry. These operations not only are capable of functionalizing traditionally unreactive positions on molecules, but provide additional strategic options for the design and implementation of synthetic routes.Due to the strength and ubiquity of these bonds, the development of methods to selectively cleave and functional groups is an important synthetic challenge. Here, efforts to use visible light as a chemical energy source to cleave C–C and C–H bonds selectively are outlined, with both single-electron oxidation and single-electron reduction as the key activation event.The first two chapters of this thesis outline the factors which can be leveraged for the functionalization of atoms alpha to amine nitrogens. Upon single-electron oxidation of an amine to its corresponding radical cation, the bond strengths to all adjacent α-positions drop substantially, providing significant modulation of reactivity through a simple oxidation mechanism. This activation pathway can be used to selectively cleave C–C bonds in the presence of significant strain energy. In the absence of strain energy, C–H bonds react in preference. Both of these activation mechanisms are demonstrated in the semi-synthesis of three alkaloid natural products using photoredox catalysis.Aside from single-electron oxidation, this work also details a reductive mechanism for the selective C–C bond cleavage of carboxylic acids. Through the use of pyridine N-oxide, a method has been developed to activate carboxylate esters to single-electron reduction, which is rapidly succeeded by a decarboxylative fragmentation event. This method has been used to trifluoromethylate a wide array of aromatic substrates, and has been demonstrated on significant scale. Mechanistic insights into this reactivity have revealed that under certain conditions intermolecular charge-transfer complexes can be formed, and these have been directly implicated in the trifluoromethylation reaction mechanism.

[发布机构] University of Michigan

[效力级别] Chemistry

[关键词] photoredox catalysis;Chemistry;Science;Chemistry