Reactivity vs. Selectivity of Biomimetic Catalyst Systems of the Fe(PDP) Family through the Nature and Spin State of the Active Iron-Oxygen Species.

Catalytic approaches to late-stage creation of new C-O bonds, especially via oxygenation of particular C-H groups in complex organic molecules, provide challenging tools for the synthesis of biologically active compounds and candidate drugs. In the last decade, significant efforts were invested in designing bioinspired iron based catalyst systems, capable of conducting selective oxidations of organic compounds. The key role of the oxygen-transferring high-valent iron-oxygen species in selective oxygenation is now well established; the next logical step would be gaining insight into the factors governing the oxidation chemo- and stereoselectivity, in relation to the peculiarities of their electronic structure, which would allow introducing the desired level of predictability into those catalytic transformations. In this Personal Account we analyze recent data on the reactivity of bioinspired formally oxoiron(V) catalytically active sites toward organic substrates having C=C and C(sp3 )-H groups. While the majority of reported oxoiron(V) active species are low-spin (S=1/2) complexes, the presence of strong electron-donating groups (NR1 R2 ) in the ligand backbone favors the high-spin (S=3/2) ground state. Remarkably, the high-spin perferryl species exhibit higher chemo-, regio-, and stereoselectivity in the oxidations than their low-spin counterparts, thus witnessing the significance of these subtle electronic effects for the selectivity of oxidations conducted by bioinspired catalysts of the Fe(PDP) family.

Low-Spin and High-Spin Perferryl Intermediates in Non-Heme Iron Catalyzed Oxidations of Aliphatic C-H Groups.

The selectivity patterns of iron catalysts of the Fe(PDP) family in aliphatic C-H oxidation with H2 O2 have been studied (PDP=N,N'-bis(pyridine-2-ylmethyl)-2,2'-bipyrrolidine). Cyclohexane, adamantane, 1-bromo-3,7-dimethyloctane, 3,7-dimethyloctyl acetate, (-)-acetoxy-p-menthane, and cis-1,2-dimethylcyclohexane were used as substrates. The studied catalyst systems generate low-spin (S=1/2) oxoiron(V) intermediates or high-spin (S=3/2) oxoiron(V) intermediates, depending on the electron-donating ability of remote substituents at the pyridine rings. The low-spin perferryl intermediates demonstrate lower stability and higher reactivity toward aliphatic C-H groups of cyclohexane than their high-spin congeners, according to the measured self-decay and second-order rate constants k1 and k2 . Unexpectedly, there appears to be no uniform correlation between the spin state of the oxoiron(V) intermediates, and the chemo- and regioselectivity of the corresponding catalyst systems in the oxidation of the considered substrates. This contrasts with the asymmetric epoxidations by the same catalyst systems, in which case the epoxidation enantioselectivity increases when passing from the systems featuring the more reactive low-spin perferryl intermediates to those with their less reactive high-spin congeners.

EPR, 1H and 2H NMR, and reactivity studies of the iron-oxygen intermediates in bioinspired catalyst systems.

Complexes [(BPMEN)Fe(II)(CH(3)CN)(2)](ClO(4))(2) (1, BPMEN = N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)-1,2-diaminoethane) and [(TPA)Fe(II)(CH(3)CN)(2)](ClO(4))(2) (2, TPA = tris(2-pyridylmethyl)amine) are among the best nonheme iron-based catalysts for bioinspired oxidation of hydrocarbons. Using EPR and (1)H and (2)H NMR spectroscopy, the iron-oxygen intermediates formed in the catalyst systems 1,2/H(2)O(2); 1,2/H(2)O(2)/CH(3)COOH; 1,2/CH(3)CO(3)H; 1,2/m-CPBA; 1,2/PhIO; 1,2/(t)BuOOH; and 1,2/(t)BuOOH/CH(3)COOH have been studied (m-CPBA is m-chloroperbenzoic acid). The following intermediates have been observed: [(L)Fe(III)(OOR)(S)](2+), [(L)Fe(IV)═O(S)](2+) (L = BPMEN or TPA, R = H or (t)Bu, S = CH(3)CN or H(2)O), and the iron-oxygen species 1c (L = BPMEN) and 2c (L = TPA). It has been shown that 1c and 2c directly react with cyclohexene to yield cyclohexene oxide, whereas [(L)Fe(IV)═O(S)](2+) react with cyclohexene to yield mainly products of allylic oxidation. [(L)Fe(III)(OOR)(S)](2+) are inert in this reaction. The analysis of EPR and reactivity data shows that only those catalyst systems which display EPR spectra of 1c and 2c are able to selectively epoxidize cyclohexene, thus bearing strong evidence in favor of the key role of 1c and 2c in selective epoxidation. 1c and 2c were tentatively assigned to the oxoiron(V) intermediates.

EPR spectroscopic trapping of the active species of nonheme iron-catalyzed oxidation.

The key intermediate of a bioinspired iron catalyst for selective hydrocarbon oxidation based on hydrogen peroxide and an iron complex with a tetradentate aminopyridine ligand was trapped by EPR. On the basis of EPR and reactivity data this intermediate is tentatively proposed to be an oxoiron(V) complex.