Synthesis and application of supramolecular catalysts in the oxidation of unactivated C(spᵌ)-H bonds

English Abstract
Over recent decades, impressive progress was achieved in the selective functionalization of unactivated aliphatic C(sp3)-H bonds. Considering the inert character and ubiquity of these bonds, they are considered among the most challenging ones to selectively convert. However, at the same time, the selective reaction of C-H bonds, especially in the form of late-stage functionalizations, has great potential and is very attractive from an economic point of view. Synthetic chemists have established different approaches to achieve good activity and selectivity in C-H oxidations, including directed, undirected, and supramolecular strategies. To us, the supramolecular approach, in which binding between the catalyst and the substrate is achieved via multiple weak forces, was of great interest in particular.
In the first part of this thesis, supramolecular catalysts consisting of a glycoluril-based molecular tweezer and well-established M(pdp) or M(mcp) catalysts were prepared. In total, five different versions were synthesized in ten steps each. In all cases, preferential oxidation of decylammonium at the intrinsically deactivated positions close to the ammonium salt was observed (C3/C4). However, slightly different results were obtained depending on the catalyst used. The best results regarding the selectivity for the deactivated positions C3/C4 were achieved with Fe(pdp)Twe. Other than decylammonium, a handful of other linear aliphatic ammonium salts, two ammonium substrates possessing a terpene substitution pattern, and two cyclohexane derivatives were investigated in the oxidation with Fe(pdp)Twe. Finally, we also studied the oxidation behavior of our catalyst in different solvents (MeCN, TFE, HFIP).
In the second part, the non-heme Mn(mcp) catalyst was functionalized with two distinct cyclophane moieties, leading to Mn(mcp)CY3 and Mn(mcp)CY5. The catalysts were both made in a seven-step synthesis. We hypothesized that selective oxidations of aliphatic substrates lacking any functional handle might be possible in TFE and HFIP, due to a solvophobic effect. Unfortunately, we observed the same oxidation pattern with our supramolecular catalysts as with the unfunctionalized Mn(mcp) for all investigated substrates. However, it should be noted that the work on this concept is ongoing and that promising first results have been observed by another group member with different macrocycles.