Selectivity in C–​H versus C–​F Bond Oxygenation by Homo- and Heterometallic Fe₄, Fe₃Mn, and Mn₄ Clusters

The versatility by which iron-​containing metalloenzymes are able to activate and oxygenate C–​H bonds with molecular oxygen has sparked much interest in the underlying mechanism. It has been shown that high-​valent iron metal centers bearing terminal metal-oxo motifs are commonly invoked in the oxygenation step, and their formation has been studied in many monometallic iron model complexes. Despite the intense research efforts, terminal metal-oxo motifs on multi-​metallic scaffolds are rare. Recently, we presented a new class of tetra-​iron complexes that are site differentiated. In these complexes, three six-​coordinate iron centers form a trimetallic “core” that is connected to a fourth unique coordinatively unsaturated apical iron center. We have also shown that treating – for example – [LFe₃(PhPz)​₃OFe]​[OTf]​₂ (PhPz = Ph pyrazolate) with oxygen-​atom transfer reagents (e.g. Iodosobenzene or TBAIO₄) results in regioselective intramolecular hydroxylation of an arene C–​H bond. These reactivity patterns suggest the involvement of a rare Fe^IV-​oxo motif on well-​defined multi-​metallic scaffold. Here we show that treating a partially fluorinated analog [LFe₃(HFPhPz)​₃OFe]​[OTf]​₂ (HFPhPz = 2-fluorophenyl pyrazolate) with oxygen atom transfer reagents almost exclusively results in the oxygenation of the C–​F bond in the presence of other accessible C–H bonds. Such selectivity is highly unusual. First and foremost, intramolecular C–F bond oxygenation with terminal metal-oxo motifs are rare, and second, P450 enzymes preferentially oxygenate C–H bonds in the presence of other C–F bonds. However, upon exchanging the apical iron metal center for manganese, the selectivity is reversed. With manganese as apical metal center, the arene C–H bond is preferentially oxygenated (Figure 1). The selectivity and reactivity of the different metal clusters will be discussed in light of potential intramolecular electron transfer pathways that are able to alter the reactivity of terminal iron-​oxo species (e.g. M^IV-​O vs. M^III-​O).

Figure 1. Metal dependent selectivity in intramolecular C-X bond oxygenation (X = H or F) by tetranuclear metal complexes