Transition Metal Catalyzed Carbon-Heteroatom Bond Formations

Abstract

Die Dissertation ist bis zum 13. September gesperrt !

The following cumulative thesis showcases strategies for mild transition metal catalyzed carbon-heteroatom bond formations, including C-S bonds via cross-coupling and C-I bonds via epimerization. An introduction and literature overview, as well as a summary of published and unpublished results, in addition to the published scientific articles with their corresponding supporting information are included. Transition metal catalysis enables a plethora of transformations, generating valuable synthetic products. One example is the C-S cross-coupling of aryl and alkenyl (pseudo)halides with alkyl thiols, generating thioethers, a compound class with widespread application in materials, agrochemicals and pharmaceuticals. An efficient synthesis of these high value compounds, by employing the air-stable, low-cost pre-catalyst XantphosNi(o-tolyl)Cl and KOAc as base at room temperature, is the main focus of this thesis. The first project focused on the coupling of aryl chlorides, showcasing a scope of 50 examples with excellent yields and functional group tolerance. A variety of alternative aryl (pseudo)halides were successfully employed as electrophiles, demonstrating the versatility of the system. Chemoselective functionalization of di-substituted aryl (pseudo)halides enabled selective mono-coupling as well as sequential multi-functionalization. Subsequently, the methodology was expanded to aryl and alkenyl triflates, synthesized in a straight-forward, one-step procedure from abundant phenols and ketones, with a scope of 38 examples, exhibiting superior reactivity and yields. Additionally, the applicability of the catalytic system for late-stage functionalization of pharmaceutically active or biorelevant compounds was demonstrated. Mechanistic investigations, including kinetic and NMR-studies, as well as DFT calculations, supporting a Ni(0)/Ni(II) catalytic cycle, were conducted. Furthermore, a comparison of various one-component pre-catalysts, as well as preliminary experiments towards enantioselective C-S cross-coupling are included. The second part of this thesis showcases stereochemical C-I bond editing in a palladium catalyzed epimerization under blue light irradiation (465 nm LED) from the exo to endo face of norbornene model compounds with 17 examples and endo selectivity up to > 20:1. Mechanistic studies and DFT calculations support a reversible C-I bond formation through a thermodynamically driven epimerization.