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

Oxidation of the iron(II) precursor [(L1 )FeII Cl2 ], where L1 is a tetradentate bispidine, with soluble iodosylbenzene (s PhIO) leads to the extremely reactive ferryl oxidant [(L1 )(Cl)FeIV =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 s 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 Fe2+ and Fe3+ in comparison with [(L1 )FeII Cl2 ] 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, [(L1 )(Cl)FeIV =O]+ is the most reactive small-molecule halogenase model, that the FeIII /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.

Pathways of the Extremely Reactive Iron(IV)-oxido complexes with Tetradentate Bispidine Ligands.

The nonheme iron(IV)-oxido complex trans-N3-[(L1 )FeIV =O(Cl)]+ , where L1 is a derivative of the tetradentate bispidine 2,4-di(pyridine-2-yl)-3,7-diazabicyclo[3.3.1]nonane-1-one, is known to have an S=1 electronic ground state and to be an extremely reactive oxidant for oxygen atom transfer (OAT) and hydrogen atom abstraction (HAA) processes. Here we show that, in spite of this ferryl oxidant having the "wrong" spin ground state, it is the most reactive nonheme iron model system known so far and of a similar order of reactivity as nonheme iron enzymes (C-H abstraction of cyclohexane, -90 °C (propionitrile), t1/2 =3.5 sec). Discussed are spectroscopic and kinetic data, supported by a DFT-based theoretical analysis, which indicate that substrate oxidation is significantly faster than self-decay processes due to an intramolecular demethylation pathway and formation of an oxido-bridged diiron(III) intermediate. It is also shown that the iron(III)-chlorido-hydroxido/cyclohexyl radical intermediate, resulting from C-H abstraction, selectively produces chlorocyclohexane in a rebound process. However, the life-time of the intermediate is so long that other reaction channels (known as cage escape) become important, and much of the C-H abstraction therefore is unproductive. In bulk reactions at ambient temperature and at longer time scales, there is formation of significant amounts of oxidation product - selectively of chlorocyclohexane - and it is shown that this originates from oxidation of the oxido-bridged diiron(III) resting state.

Spin state and reactivity of iron(iv)oxido complexes with tetradentate bispidine ligands.

The iron(iv)oxido complex [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ is shown by experiment and high-level DLPNO-CCSD(T) quantum-chemical calculations to be an extremely short-lived and very reactive intermediate-spin (S = 1) species. At temperatures as low as -90 °C, it decays with a half-life of approx. two minutes, and this is the reason why, so far, it remained undetected and why it is extremely difficult to trap and fully characterize this interesting and extremely efficient oxidant. The large difference in reactivity between [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ and [(bispidine)FeIV[double bond, length as m-dash]O(MeCN)]2+ (at least two orders of magnitude), while both oxido-iron(iv) complexes have very similar structures and an S = 1 electronic ground state, is presumably due to the large difference in the energy gap between the triplet and quintet electronic states. In presence of cyclohexane as substrate, [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ oxidizes cyclohexane with a rate that is approx. 25 times faster than the self-decay of the oxidant, and selectively leads to chlorocyclohexane in moderate yield. The S = 1 electronic ground state of [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ and a relatively low gap to the S = 2 state (approx. 6 kJ mol-1vs. approx. 75 kJ mol-1 for [(bispidine)FeIV[double bond, length as m-dash]O(MeCN)]2+) is also predicted by DLPNO-CCSD(T) quantum-chemical calculations. The method used was benchmarked with a set of six ferryl complexes with experimentally known electronic ground states.