Aerobic Oxidative N-Heterocyclic Carbene Catalysis via Multistep Electron Transfer - Method Development and Applications

Licentiate thesis, 2017

Oxidation reactions are ubiquitous in synthetic chemistry, but generally suffer from formation of large amounts of potentially toxic byproducts. Aerial oxygen represents an ideal oxidant since it is inexpensive, non-toxic and only forms water as a byproduct. However, aerobic oxidations are characterized by high activation barriers leading to formation of kinetic side products. A common way to circumvent this is by introducing electron transfer mediators (ETMs) to achieve a kinetically useful reaction. N-heterocyclic carbenes (NHCs) are an important group of organocatalysts that have been used in a wide range of both redox neutral and oxidative transformations. In this thesis, an ETM strategy is used to enable aerobic NHC catalysis. The developed protocol has been employed in aerobic esterifications yielding a,b-unsaturated esters of industrial importance in good to excellent yields. The ETM strategy was also extended to both the racemic and asymmetric synthesis of dihydropyranones. Lastly, an organocatalytic valorization of the sustainable feedstock glycerol was developed. The reaction furnished several highly functionalized glycerol derivatives in one step from sustainable resources, and could also be extended to the synthesis of 2-oxooxazolidine esters. To summarize, the combination of ETMs and NHC catalysis enable the use of aerial oxygen as the terminal oxidant in distinct reaction pathways, with water as the only byproduct.