N-Heterocyclic Carbene Catalysis in Organic Synthesis - A Green Chemistry Approach
The twelve principles of green chemistry were created as a response to the multiple environmental issues caused by the release of waste from the chemical industry. The principles acts as a guide in the development of sustainable chemical processes for the syntheses of important molecules needed to sustain our living standards. This thesis will focus on the most important principle, catalysis, which can aid in making reactions more efficient and atomeconomic, hence reducing the formation of chemical waste. One type of catalyst is the N-heterocyclic carbene (NHC), a type of organocatalyst that has become an attractive tool for the synthesis of various interesting compounds. Two different methods of using NHC catalysis are presented.
The first method uses an imidazolium-based ionic liquid as an NHC-precatalyst for the synthesis of oxo triphenylhexanoates (OTHOs) in a highly stereo- and regioselective manner. The scope of the reaction is broad, with multiple functional groups tolerated. With this method, the selective modification of complex polyols, such as carbohydrates is possible. The reaction operates under mild conditions, can be performed in a one-pot multicomponent reaction without the use of protecting groups, and omits the use of solvent-demanding chromatography by a simple filtration work-up procedure.
The second method employs oxidative NHC catalysis for the synthesis of various α,β unsaturated esters, lactones, and acylated N-heterocyclic compounds such as indoles and oxazolidinones. An aerobic protocol was developed with the help of electron transfer mediators (ETMs) enabling the use of molecular oxygen as the terminal oxidant. This aerobic protocol allows for the substitution of a high molecular weight oxidant frequently associated with oxidative NHC catalysis. The developed method facilitates scale-up reactions and reduction of the chemical waste generated. The obtained products were also applied in further functionalization towards commercially interesting compounds.
This thesis demonstrates the use of catalysis for the development of reactions that are atomeconomic, energy efficient and avoid the creation of chemical waste. Moreover, with NHC catalysis readily available reagents could be utilized as starting materials, thus avoiding hazardous substrates. By the guidance of the principles of green chemistry more sustainable and benign reactions can be designed.
oxidative NHC catalysis