Synthesis and Characterization of η⁶-Arene-Ruthenium(II)-Complexes and their Application in Catalysis Based on Arene-Exchange

Late-stage functionalization (LSF) of small and complex organic molecules is an indispensable method for rapid exploration of the structure-activity relationship (SAR) and absorption distribution excretion metabolism (ADME) properties of drug-candidates. Finding methods for LSF that are easily applicable, chemo- and regioselective and suitable for a broad substrate scope is thus a highly desired goal for synthetic organic chemists. Especially, the direct C–H-functionalization of arenes is a relevant field of LSF due to the ubiquitous presence of arene-moieties in molecules that are relevant for the pharmacological industry. Many current C–H-functionalization methods suffer from several drawbacks, such as lack of selectivity, requirement of directing groups, harsh conditions or a small substrate scope. To overcome these challenges, new methods for direct C–H-functionalization of arenes are searched by both, academic and industrial research facilities. A rather unconventional method for the functionalization of arenes is the π-coordination to a transition metal. The formation of a π-arene complex leads to several useful properties of the coordinated arene, such as increased electrophilicity, acidity and site-selectivity. Thus, the coordination to a transition metal can be used to activate arenes for functionalization reactions. This work deals with the design and development of catalytic systems for arene functionalization that are based on η6-arene ruthenium complexes. Three conceptually different families of π-arene complexes are synthesized and analyzed, which are namely anionic ruthenium complexes, DPPPentanalogues and ruthenium–hydride complexes. All synthesized complexes are evaluated concerning their ability to perform arene-exchange as the key-step for catalytic functionalization. Moreover, the synthesized complexes are tested as catalysts in reactions that involve arene-exchange, such as nucleophilic aromatic substitutions (SNAr-reactions). A novel dinuclear ruthenium complex with a bridging N-heterocyclic carbene (NHC) and two bridging chlorine atoms is presented as the results of the synthetic examination of analogues to DPPPent. Furthermore, an unexpected asymmetric η6-cymene ruthenium complex is synthesized and characterized, which suggests the geometrical possibility of a multidentate coordination of PPh3- derived ligands. In this multidentate fashion, the ruthenium metal is coordinated simultaneously to the phosphorus atom and a phenyl ring. The coordination pattern inspired the proposal of a new mechanism for the arene-exchange process. Out of the unity of catalytically active complexes, a ruthenium–hydride complex is demonstrated to actively perform arene-exchange even with unfavored substrates and is therefore applied several attempts for direct C–H-functionalization