Non-Heme-Iron-Mediated Selective Halogenation of Unactivated Carbon-Hydrogen Bonds

Oxidation of the iron(II) precursor [(L )Fe Cl ], where L is a tetradentate bispidine, with soluble iodosylbenzene ( PhIO) leads to the extremely reactive ferryl oxidant [(L )(Cl)Fe =O] with a cis disposition of the chlorido and oxido coligands, as observed in non-heme halogenase enzymes. Experimental data indicate that, with cyclohexane as substrate, there is selective formation of chlorocyclohexane, the halogenation being 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 PhIO oxidation of an initially formed oxido-bridged diiron(III) resting state. The high yield of up to >70 % (stoichiometric reaction) as well as the differing reactivities of free Fe and Fe in comparison with [(L )Fe Cl ] indicate a high complex stability of the bispidine-iron complexes. DFT analysis shows that, due to a large driving force and small triplet-quintet gap, [(L )(Cl)Fe =O] is the most reactive small-molecule halogenase model, that the Fe /radical rebound intermediate has a relatively long lifetime (as 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; this is shown to primarily be due to steric effects.