N-Heterocyclic carbenes (NHCs) are the ligands of choice in a large variety of transformations entailing different transition metals. However, the number of chiral NHCs suitable as stereocontrolling ligands in asymmetric catalysis remains limited. In particular, a chiral version of the widely applied IPr may be of use for a large variety of asymmetric transformations. This thesis focuses on the introduction of a modular NHC ligand family, resembling a chiral version of IPr, and their application in nickel catalyzed enantioselective C-H functionalizations of N-heterocycles.
Nickel-NHC catalysis enabled the C-H annulation of 2- and 4-pyridones, delivering fused bicyclic compounds found in many biologically active compounds. Crucial to the transformation was the introduction of a sterically hindered and tuneable chiral NHC. Applying this bulky, yet flexible ligand scaffold enabled the highly enantioselective C-H functionalization of pyridones under mild conditions.
The introduction of a bulky chiral SIPr analogue enabled the nickel catalyzed enantioselective C-H functionalization of indoles, yielding valuable tetrahydropyridoindoles. The process is characterized by a clear endo-cyclization preference to form the sought-after six-membered-ring annulated N-heterocycles without the need for the typically applied Lewis basic directing groups. Additionally, pyrrolopyridines, pyrrolopyrimidines and pyrroles were efficiently functionalized, delivering chiral annulated azoles.