Mechanochemical sp$^{3}$ C−H functionalizations in ball mills

  • Mechanochemische sp$^{3}$ C−H Funktionalisierungen in Kugelmühlen

Weißbach, Ulla; Bolm, Carsten (Thesis advisor); Albrecht, Markus (Thesis advisor)

Aachen : RWTH Aachen University (2021, 2022)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2021

Abstract

In this thesis, the mechanochemical activation of sp$^{3}$ C−H bonds in the ball mill was investigated. Four different functionalizations are discussed. In the first part, the arylation of quinoline substrates was studied. Thus, aryl iodide, phenylhydrazine and boronic acids or derivatives thereof were explored as arylating agents. Also, a cross-dehydrogenative coupling, also known as double C−H activation, using unactivated arenes was investigated. The second part of this thesis concentrated on the selective amidation of sp$^{3}$ C−H bonds. Here, various metals catalysts were screened, revealing a rhodium-catalyzed approach using dioxazolones as the most viable option for the conversion of model compound 8-methylquinoline. The respective products were obtained after simple purification by column chromatography. Aside from different quinolines and dioxazolones, the scope also includes a substrate bearing an O-methyloxime directing group. In the third part, a selective sp$^{3}$ C−H acylation was envisioned. A palladium-catalyzed protocol employing the hypervalent iodine reagent PhI(OAc)$_{2}$ in combination with the use of acetic acid as a LAG (liquid-assisted grinding) additive afforded the desired products in good yield. The scope of the reaction included not only different substituted quinolines but also 2-acetylthiazole as substrates. Furthermore, a scale-up of the transformation by the factor 5 was realized. Here, the selectivity could be retained, and the yield was only minorly reduced. The last part of this thesis aimed at the selective sp$^{3}$ C−H halogenation of model compound 8-methylquinoline. In this regard, three different approaches were tested. Unfortunately, neither succinimides, nor a copper halogenate or a trihaloisocyanuric acid proved to be viable halogenating agents under the applied reaction conditions.

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