h1

%0 Thesis
%A Schoetz, Markus D.
%T Oxidative functionalization of aryl and alkyl germanes
%I RWTH Aachen University
%V Dissertation
%C Aachen
%M RWTH-2025-05202
%P 1 Online-Ressource : Illustrationen
%D 2025
%Z Veröffentlicht auf dem Publikationsserver der RWTH Aachen University
%Z Dissertation, RWTH Aachen University, 2025
%X Sequential and programmable strategies for accessing highly substituted arenes are of significant interest for accelerating the discovery of new potential drug candidates. Palladium-catalyzed couplings have revolutionized the way chemists assemble molecules in a selective manner. Typically, established functionalities such as transmetalation handles or (pseudo)halides are employed. While these reaction pathways offer powerful approaches, they often operate within similar reaction regimes, limiting the potential for orthogonal coupling strategies. In the first chapter aryl germanes were introduced as a suitable handle for orthogonal olefination through an oxidative Heck-type coupling under straightforward and efficient reaction conditions (Figure 1). The corresponding Heck product was achieved with high E/Z selectivity in an orthogonal fashion, even in the presence of C-Bpin or C-SiMe3 bonds. Reactive halides such as aryl iodides were tolerated. This enabled orthogonal couplings at the C-Ge site under the newly developed reaction conditions or, alternatively, selective couplings at the C-I site using established methods. Ultimately, an arene building block with three distinct functional handles was successfully employed, allowing for sequential functionalization at each of the three sites in a streamlined downstream process. Orthogonal functionalization in 2D space (i.e. at C(sp²) centers) is generally easier to achieve because certain functional groups show different reactivity in this environment. In contrast, the same functional groups in 3D space (i.e. at C(sp³) centers) show less variation in reactivity, making orthogonal functionalization more challenging. Therefore, in the second chapter the -GeEt3 motif was introduced as a suitable orthogonal partner in 3D space under photoredox conditions (Figure 2). To demonstrate this, a 3D building block was synthesized featuring three distinct functional handles (C-Cl, C-Bpin, and C-GeEt3) on a single carbon atom, enabling sequential orthogonal functionalization of each position for the first time. Initial C-C and C-heteroatom couplings were performed at the C–Cl site, followed by oxidation, homologation, amidation and arylation at the C-Bpin site. On the C-Ge site, C-C coupling was achieved through Giese addition, as well as nickel-catalyzed arylation for completion of the sequence. Additionally, the limited functionalization strategies of alkyl germanes were expanded to include four new decorations using sulfonyl trapping reagents, enabling the formation of C-SPh, C-heteroaryl, C-Cl, and C-N3 bonds. Furthermore, asymmetric arylations were successfully achieved for the first time using a chiral nickel catalyst under photoredox conditions. In the final chapter, challenges associated with the previously limited options for C-heteroatom bond formation of alkyl germanes were addressed (Figure 3). A novel strategy was developed, involving a radical polar crossover from a nucleophilic alkyl radical to an electrophilic carbocation via subsequent oxidation under electrochemical conditions. This transformation allows the carbocation to be trapped by various nucleophiles, including heteroatom-based ones. This method proceeds under simple conditions using different tertiary, secondary, benzylic and α-heteroatom germanes. The electrochemical functionalization strategy enables C-O, C-N, C-S, C-P, C-F and C-C couplings with substrates such as natural products and protected amino acids, while retaining their stereochemical integrity. Moreover, it was demonstrated that the previously developed 3D platform could be employed for C-heteroatom bond formation, thereby completing the sequence and ultimately expanding decoration options through a general approach to access C-heteroatom bonds.
%F PUB:(DE-HGF)11
%9 Dissertation / PhD Thesis
%R 10.18154/RWTH-2025-05202
%U https://publications.rwth-aachen.de/record/1012834