Catalyst Controlled Site-Selective Carbon-Hydrogen Functionalization

The development of mild and selective methods for the functionalization of arene C--H bonds remains an important challenge in organic chemistry. One strategy to achieve this goal is metal-catalyzed C--H functionalization. Significant progress has been made with substrates possessing chelating directing groups that achieve metal-catalyzed C--H functionalization at sites proximal to the directing groups. In contrast, relatively few examples of selective C--H activation of simple arenes have been reported. The goal of this dissertation was to develop catalysts that promote C--H activation and site-selective functionalization of arene C--H bonds in substrates that do not contain directing groups.;In the first half of this dissertation, we explore Pt-catalyzed H/D exchange between benzene and acidic deuterium sources as a metric for directly comparing the reactivity of different Pt C--H activation catalysts. Using this assay, we compare the reactivity of known Pt C--H activation catalysts with bi- and tridentate nitrogen ligands and elucidate trends in reactivity. In the course of these studies, N-aryl diimine Pt dichloride complexes with ortho-halogen substitution of the aryl group were identified as superior C--H activation precatalysts.;In the second half of this dissertation, we discuss our results to develop site-selective C--H functionalization reactions. Our approach is to use steric and electronic modification of ancillary ligands of the metal catalyst to both modulate reactivity and dictate the preferred site of C--H activation. N-aryl diimine Pd dichloride complexes were found to efficiently and site-selectively catalyze the arylation of naphthalene to afford 1-phenyl-naphthalene. Furthermore, the yield and selectivity of this reaction can be modulated by modification of the L- and X-type ligands of the catalysts. Evidence for an unusual mechanism of C--H activation at a high oxidation state Pd IV center is also presented. Additionally, this transformation was studied with a metal organic framework supported heterogeneous Pd catalyst in collaboration with Professor Adam Matzger's laboratory. Finally, the use of commercially available platinum salts under modified reaction conditions affords both a pathway to selective formation of 2-phenyl-naphthalene, as well as promising initial results for wider arene substrate scope.