Transition Metal-Mediated Selective Functionalizations of Bio-Derived Building Blocks

In order to transition to a more sustainable chemical industry, it is necessary to replace the fossil starting materials that are largely used today with renewable ones. Starting materials available from abundant natural sources, or which can be efficiently produced via a biotransformation, are of high interest in this regard. The building blocks obtained from nature often differ from those derived from petroleum, both in composition and structure, and when the raw materials change, the chemistry we use needs to follow. Developing new ways to selectively modify these bio-derived starting materials is therefore of great importance. In this thesis, new methods for the selective functionalization of bio-derivable molecules are presented, with focus on materials available in bulk or which can be harnessed from a biotransformation. The goal is to produce new classes of chemicals which can be useful in various applications and to use the synthetic handles present in the starting materials to efficiently introduce a high degree of complexity. The first part of this thesis concerns the iron-mediated nucleophilic addition to cationic iron carbonyl dienyl complexes. The scope of this reaction was expanded to include the selective C- or O-addition of phenols. Phenolic molecules are interesting as green building blocks, as they can be obtained in large quantities from lignin byproducts of the pulp and paper industry. In addition, azulenes were also shown to be competent nucleophiles in the addition reaction, where the azulene scope included guaiazulene, available from natural sources, and derivatives thereof. Azulenes have sparked a large recent interest due to their potential for applications in optoelectronic devices such as solar cells. The second method investigated in this thesis is the palladium-catalyzed selective modification of a chiral building block obtained via a biotransformation of benzoic acid. Palladium-catalyzed Heck-type arylation showed an interesting synergy with the biocatalytically derived dihydroxylated cyclohexadienes, reacting with high selectivity and achieving a transfer of valuable steric information installed in the biotransformation to the newly formed C-C bond. This palladium-catalyzed transformation was also modelled using DFT calculations. Furthermore, if an ortho-iodo benzaldehyde is used as the aryl halide coupling partner, the arylation triggers a domino reaction, forming a chiral tetrahydrofluorenone. This domino reaction installs a high degree of complexity in a single synthetic step and represents an unprecedented acylation-terminated Heck-type reaction.