Development of Aerobic Oxidative N-Heterocyclic Carbene Catalysis via Multistep Electron Transfer and its Application
Doctoral thesis, 2019
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 kinetically useful reactions.
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 acylations of a wide range of alcohols and oxazolidinones. A method for telescoped carbonation and acylation of the biobased feedstock glycerol has also been developed. The aerobic system was also extended to both the racemic and asymmetric synthesis of dihydropyranones.
Lastly, the obtained dihydropyranones were used to achieve the formal addition of acetone to unactivated Michael acceptors. The method furnishes 5-oxohexanoates and 5-oxohexanamides in good to excellent yields and proceeds through a ring-opening and retro-Claisen fragmentation sequence. The mechanism has been investigated using both kinetic and density functional theory methods, and a dual role of the catalyst is proposed.
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.
electron transfer mediator