Non-heme-iron-mediated selective halogenation of unactivated carbon-hydrogen bonds

Oxidation of the iron(II) precursor [(L 1 )Fe II Cl 2 ] with soluble iodosylbenzene s PhIO, where L 1 is a tetradentate bispidine, leads to the extremely reactive ferryl oxidant [(L 1 )(Cl)Fe IV =O] + with a cis disposition of the chlorido and oxido coligands as observed in nonheme halogenase enzymes. Experimental data indicate that, with cyclohexane as substrate, there is selective formation of chlorocyclohexane, where the halogenation is initiated by C-H abstraction and the result of a rebound of the ensuing radical to an iron-bound Cl - . The time-resolved formation of the halogenation product indicates that this primarily results from s PhIO oxidation of an initially formed oxido-bridged diiron(III) resting state. The high yield of up to over 70% (stoichiometric reaction) as well as the differing reactivities of free Fe 2+ and Fe 3+ in comparison with [(L 1 )Fe II Cl 2 ] indicate a high complex stability of the bispidine-iron complexes. A DFT analysis shows that, due to a large driving force and small triplet-quintet gap, in comparison to other small molecule halogenase models [(L 1 )(Cl)Fe IV =O] + is the most reactive, that the Fe III / radical rebound intermediate has a relatively long lifetime, supported by experimentally observed cage escape, and that this intermediate has, as observed experimentally, a lower energy barrier to the halogenation than the hydroxylation product, and this is shown to primarily be due to steric effects.