Nondirected C(sp2)–H Activation of (Hetero-)Arenes Through Ligand-Enabled Palladium Catalysis

The overall aim of this thesis was the development of innovative ligands for Pd-catalyzed nondirected C–H activation, which enable new reactivities and transformations.

The first chapter deals with the historical development of a palladium-based catalyst system consisting of two complementary ligands, which efficiently enables C–H activation of arenes and subsequent C–H functionalization through diverse follow-up steps. 

The second chapter describes attempts to develop catalysts for the nondirected fluorination of arenes. While a suitable combination of a dual-ligand based catalyst system and an oxidant could be identified throughout these studies, the yield could not be optimized. Further studies therefore focused on the development of innovative ligands with enhanced reactivity.

An optimal way to evaluate new ligands while simultaneously establishing useful synthetic methods are deuteration studies. Chapter 3 shows how newly prepared ligands were used to develop a broadly applicable method for the per-deuteration of several classes of heteroarenes. Reaction optimization was performed using a multi-substrate-screening approach, which allowed for the identification of optimal reaction conditions for different classes of heteroarenes from a minimal amount of screening reactions. Investigations of the substrate scope demonstrated the broad applicability of the method.

Chapter 4 deals with the development of new ligand systems for the alkoxycarbonylation of arenes. The newly developed system enabled the synthesis of synthetically versatile active esters starting from simple arenes under steric control of regioselectivity. Exploration of the substrate scope demonstrated broad applicability and mechanistic studies led to a sound mechanistic hypothesis.

Chapter 5 describes the synthesis and development of unprecedented tridentate ligands as new ligand class, which has the potential to stabilize high-valent Pd-species and thereby enable challenging transformations. A large variety of ligands were synthesized and evaluated through deuteration studies. The most active of these tridentate ligands showed higher catalytic activity than established dual-ligand based systems, which further stresses the tremendous potential of this class of ligands.