2014

Leskinen, Mikko

The research described in this thesis focuses on the remote catalytic oxidative functionalization of sp3 C-H bonds. The goal of the work was to develop a new method for the crossdehydrogenative coupling of β-keto esters and indoles. The basic aims of the study were successfully realized, and a new oxidative remote sp3 β'-C-H functionalization platform was created. The reactions were found to work under benign conditions at room temperature. Cross-dehydrogenative coupling reactions between β-keto esters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of β-keto esters and indoles. The mechanism of the reaction between a prototypical β-keto ester, ethyl 2-oxocyclopentanonecarboxylate and N-methylindole, has been studied experimentally by monitoring the temporal course of the reaction by 1H NMR, kinetic isotope effect studies, and control experiments. The experimental results indicate that the reaction proceeds via two catalytic cycles. Cycle A, the dehydrogenation cycle, produces an enone intermediate. The dehydrogenation is assisted by N-methylindole, which acts as a ligand for Pd(II). The coupling is completed in cycle B, the C-C bond formation cycle, which is catalyzed by Pd(II) and also by trifluoroacetic acid.