Dual Ligand-Enabled Palladium Catalysis: Unlocking Novel Reactivities and Selectivities in Aromatic C–H Activation

ongoing

The transition metal catalyzed activation of aromatic carbon-hydrogen (C–H) bonds has enabled a variety of novel transformations that complement traditional approaches towards complex aromatic compounds. The vast majority of methods developed in this field relies on the use of directing groups, which coordinate the catalyst prior to the C–H activation step to induce activity and selectivity. In contrast, nondirected methods have remained underdeveloped, since it has remained highly challenging to achieve reactivity and induce good selectivities in such processes. My research group has recently discovered a new design paradigm for palladium catalysts, which exhibit extraordinary activities and selectivities. Through the combined action of two complementary ligands these catalysts enable the activation of arenes without requiring a directing group or the use of an excess of the substrate. Here, I propose to initiate a broadly conceived research project aiming at three major goals: 1) The development of highly active palladium catalysts that can activate even the most challenging arene substrates. This goal will be pursued by building a broad ligand library and conducting systematic structure activity studies that are designed to deliver an in-depth mechanistic understanding. 2) The development of catalysts that enable high sterically controlled regioselectivities. This goal will be tackled using a mechanism-based design approach, aiming to minimize the influence of electronic effects and to suppress unintended directing effects. 3) The development of novel synthetic methods for late-stage functionalization. A particular focus will be on transformations that exhibit otherwise challenging regioselectivities and deliver attractive motifs for medicinal chemistry. Overall this project is expected to establish dual ligand-enabled palladium catalysis as a novel tool in synthetic organic chemistry that will prove highly useful in both academic and industrial laboratories.