Intramolecular Iron-Mediated C–H Bond Heterolysis with an Assist of Pendant Base in a [FeFe]-Hydrogenase Model

Although many metalloenzymes containing iron play a prominent role in biological C–H activation processes, to date iron-mediated C­(sp³)–H heterolysis has not been reported for synthetic models of Fe/S-metalloenzymes. In contrast, ample precedent has established that nature’s design for reversible hydrogen activation by the diiron hydrogenase ([FeFe]-H₂ase) active site involves multiple irons, sulfur bridges, a redox switch, and a pendant amine base, in an intricate arrangement to perform H–H heterolytic cleavage. In response to whether this strategy might be extended to C–H activation, we report that a [FeFe]-H₂ase model demonstrates iron-mediated intramolecular C–H heterolytic cleavage via an agostic C–H interaction, with proton removal by a nearby pendant amine, affording Fe^II–[Fe′^II–CH–S] three-membered-ring products, which can be reduced back to <b>1</b> by Cp₂Co in the presence of HBF₄. The function of the pendant base as a proton shuttle was confirmed by the crystal structures of the N-protonated intermediate and the final deprotonated product in comparison with that of a similar but pendant-amine-free complex that does not show evidence of C–H activation. The mechanism of the process was backed up by DFT calculations