Valorization of Platform Chemicals using Photoredox Catalysis

Radical chemistry is experiencing a revival in organic synthesis, and the interest has emerged especially within the field of visible light photoredox catalysis. Photoredox catalysis has been demonstrated to be a powerful synthetic technique in organic chemistry owing to its ability to generate reactivity in chemical substrates at non-traditional sites. The mild conditions used during photoredox catalysis, especially, the employment of low-energy visible light has facilitated transformations on molecules that were elusive for the organic chemist through different single electron transfer series. This thesis outlines the valorization of two different platform chemicals, namely glycerol and furfural via photoredox-catalyzed hydrogen atom transfer to accomplish a carbon-carbon bond-forming strategy.
Chapter 2 describes a method for the photocatalyzed alkylation between the second carbon on glycerol towards a variety of electron-deficient olefin acceptors. The valorization of glycerol was achieved by two different photocatalysts. With an iridium photocatalyst, it was possible to couple glycerol with acrylates, while the decatungstate catalyst allowed for further coupling to acceptors that were not possible with the iridium photocatalyst. A second project, closely related to this work, was performed, in which the hydrogen donor substrate was substituted for furfural. The decatungstate catalyst was shown to facilitate the carbon-carbon bond formation between furfural and electron-deficient olefins obtaining new bio-derived molecules.
Chapter 4 describes a project conducted during an external stay at Lundbeck. The project describes a methodology on the decarboxylative alkenylation between enol triflates and alkyl carboxylic acids. The method allows for the cross-coupling between two cheap and readily available starting materials. The cross-coupling between the two substrates is mediated by a dual photoredox catalytic cycle between nickel and the iridium photocatalyst.
Likewise, the last chapter outlines a project carried out at Lundbeck and describes the synthesis of oxabicyclooctane found to be a non-classical bioisostere of the phenyl ring. This bioisostere encompasses an oxygen atom in the core of the structure. The aim of the project is to validate oxabicyclooctane as a non-classical phenyl bioisostere by installing the moiety into different drug molecules and, thereby, study the physicochemical- and pharmacokinetic properties of the synthesized drug analogs. Additionally, the synthesized drug analogs will be compared to drug molecules encompassing bicyclooctane as a phenyl bioisostere. The synthesis of drug analogs containing the bicyclooctane core is also depicted in this thesis.