Miquel Costas

Biomimetic nonheme iron catalysts for alkane hydroxylation

Abstract The catalytic functionalization of alkanes under mild conditions is a subject of great current interest. Nature has evolved a number of metalloenzymes such as the heme-containing cytochrome P450 and the nonheme methane monooxygenase, which are capable of effecting such transformations. There has thus been significant interest in modeling such enzyme active sites and developing biomimetic alkane hydroxylation catalysts. In this review, the efforts of the last 10 years in the development of nonheme iron catalysts are summarized and discussed. These catalysts typically act in concert with ROOH or H 2 O 2 . With ROOH as oxidant, it is clear from mechanistic studies that alkoxyl radicals are the principal agents that cleave the alkane Cue5f8H bond to generate long-lived alkyl radicals. This conclusion, for the most part, applies also for oxidations involving H 2 O 2 . In a few cases, however, stereospecific alkane hydroxylation is observed. For these instances, there is evidence from H 2 18 O exchange experiments that a high-valent iron-oxo species is involved.

An FeIV=O complex of a tetradentate tripodal nonheme ligand.

The reaction of [FeII(tris(2-pyridylmethyl)amine, TPA)(NCCH3)2]2+ with 1 equiv. peracetic acid in CH3CN at −40°C results in the nearly quantitative formation of a pale green intermediate with λmax at 724 nm (ɛ ≈ 300 M−1⋅cm−1) formulated as [FeIV(O)(TPA)]2+ by a combination of spectroscopic techniques. Its electrospray mass spectrum shows a prominent feature at m/z 461, corresponding to the [FeIV(O)(TPA)(ClO4)]+ ion. The Mössbauer spectra recorded in zero field reveal a doublet with ΔEQ = 0.92(2) mm/s and δ = 0.01(2) mm/s; analysis of spectra obtained in strong magnetic fields yields parameters characteristic of S = 1 FeIVO complexes. The presence of an FeIVO unit is also indicated in its Fe K-edge x-ray absorption spectrum by an intense 1-s → 3-d transition and the requirement for an O/N scatterer at 1.67 Å to fit the extended x-ray absorption fine structure region. The [FeIV(O)(TPA)]2+ intermediate is stable at −40°C for several days but decays quantitatively on warming to [Fe2(μ-O)(μ-OAc)(TPA)2]3+. Addition of thioanisole or cyclooctene at −40°C results in the formation of thioanisole oxide (100% yield) or cyclooctene oxide (30% yield), respectively; thus [FeIV(O)(TPA)]2+ is an effective oxygen-atom transfer agent. It is proposed that the FeIVO species derives from O—O bond heterolysis of an unobserved FeII(TPA)-acyl peroxide complex. The characterization of [FeIV(O)(TPA)]2+ as having a reactive terminal FeIVO unit in a nonheme ligand environment lends credence to the proposed participation of analogous species in the oxygen activation mechanisms of many mononuclear nonheme iron enzymes.

AN FEIVO COMPLEX COMPLEX OF A TETRADENTATE TRIPODAL NONHEME LIGAND

The reaction of [FeII(tris(2-pyridylmethyl)amine, TPA)(NCCH3)2]2+ with 1 equiv. peracetic acid in CH3CN at −40°C results in the nearly quantitative formation of a pale green intermediate with λmax at 724 nm (ɛ ≈ 300 M−1⋅cm−1) formulated as [FeIV(O)(TPA)]2+ by a combination of spectroscopic techniques. Its electrospray mass spectrum shows a prominent feature at m/z 461, corresponding to the [FeIV(O)(TPA)(ClO4)]+ ion. The Mössbauer spectra recorded in zero field reveal a doublet with ΔEQ = 0.92(2) mm/s and δ = 0.01(2) mm/s; analysis of spectra obtained in strong magnetic fields yields parameters characteristic of S = 1 FeIVO complexes. The presence of an FeIVO unit is also indicated in its Fe K-edge x-ray absorption spectrum by an intense 1-s → 3-d transition and the requirement for an O/N scatterer at 1.67 Å to fit the extended x-ray absorption fine structure region. The [FeIV(O)(TPA)]2+ intermediate is stable at −40°C for several days but decays quantitatively on warming to [Fe2(μ-O)(μ-OAc)(TPA)2]3+. Addition of thioanisole or cyclooctene at −40°C results in the formation of thioanisole oxide (100% yield) or cyclooctene oxide (30% yield), respectively; thus [FeIV(O)(TPA)]2+ is an effective oxygen-atom transfer agent. It is proposed that the FeIVO species derives from O—O bond heterolysis of an unobserved FeII(TPA)-acyl peroxide complex. The characterization of [FeIV(O)(TPA)]2+ as having a reactive terminal FeIVO unit in a nonheme ligand environment lends credence to the proposed participation of analogous species in the oxygen activation mechanisms of many mononuclear nonheme iron enzymes.

Spin state tuning of non-heme iron-catalyzed hydrocarbon oxidations: participation of FeIII–OOH and FeVO intermediatesBased on the presentation given at Dalton Discussion No. 4, 10–13th January 2002, Kloster Banz, Germany.

We have found a family of non-heme iron complexes [FeII(L)(CH3CN)2] (L = tetradentate pyridine containing ligand) with cis labile sites that catalyze highly stereoselective hydrocarbon oxidations using H2O2 as oxidant. The hydrocarbon oxidation reactivity patterns of this family of catalysts divide them into two subgroups: Category A catalysts which carry out highly stereoselective alkane hydroxylation, olefin epoxidation, and olefin cis-dihydroxylation via low-spin FeIII–OOH, FeVO intermediates and Category B catalysts which form high-spin FeIII–OOH intermediates and strongly favor olefin cis-dihydroxylation in which both diol oxygen atoms derive from H2O2. 6-Methyl substituents on the ligands play an important role in tuning the spin states of the iron centers to afford a family of non-heme iron complexes nthat catalyze a remarkable array of hydrocarbon oxidation reactions.

4-nitrocatechol as a probe of a Mn(II)-dependent extradiol-cleaving catechol dioxygenase (MndD): comparison with relevant Fe(II) and Mn(II) model complexes.

Abstract. Mn(II)-dependent 3,4-dihydroxyphenylacetate 2,3-dioxygenase (MndD) is an extradiol-cleaving catechol dioxygenase from Arthrobacterglobiformis that has 82% sequence identity to and cleaves the same substrate (3,4-dihydroxyphenylacetic acid) as Fe(II)-dependent 3,4-dihydroxyphenylacetate 2,3-dioxygenase (HPCD) from Brevibacteriumfuscum. We have observed that MndD binds the chromophoric 4-nitrocatechol (4-NCH2) substrate as a dianion and cleaves it extremely slowly, in contrast to the Fe(II)-dependent enzymes which bind 4-NCH2 mostly as a monoanion and cleave 4-NCH2 4–5 orders of magnitude faster. These results suggest that the monoanionic binding state of 4-NC is essential for extradiol cleavage. In order to address the differences in 4-NCH2 binding to these enzymes, we synthesized and characterized the first mononuclear monoanionic and dianionic Mn(II)-(4-NC) model complexes as well as their Fe(II)-(4-NC) analogs. The structures of [(6-Me2-bpmcn)Fe(II)(4-NCH)]+, [(6-Me3-TPA)Mn(II)(DBCH)]+, and [(6-Me2-bpmcn)Mn(II)(4-NCH)]+ reveal that the monoanionic catecholate is bound in an asymmetric fashion (Δrmetal-O(catecholate)=0.25–0.35xa0Å), as found in the crystal structures of the E.S complexes of extradiol-cleaving catechol dioxygenases. Acid-base titrations of [(L)M(II)(4-NCH)]+ complexes in aprotic solvents show that the pKa of the second catecholate proton of 4-NCH bound to the metal center is half a pKa unit higher for the Mn(II) complexes than for the Fe(II) complexes. These results are in line with the Lewis acidities of the two divalent metal ions but are the opposite of the trend observed for 4-NCH2 binding to the Mn(II)- and Fe(II)-catechol dioxygenases. These results suggest that the MndD active site decreases the second pKa of the bound 4-NCH2 relative to the HPCD active site.

Oxoiron(IV) complexes of the tris(2-pyridylmethyl)amine ligand family: effect of pyridine α-substituents

The oxoiron(IV) complexes of two 6-substituted tris(2-pyridylmethyl)amine ligand derivatives have been generated and characterized with respect to their spectroscopic and reactivity properties. The introduction of an α-substituent maintains the low-spin nature of the oxoiron(IV) unit but weakens the ligand field, as evidenced by red shifts in its characteristic near-IR chromophore. While its hydrogen-atom abstraction ability is only slightly affected, the oxo-transfer reactivity of the oxoiron(IV) center is significantly enhanced relative to that of the parent complex. These results demonstrate that the ligand environment plays a key role in modulating the reactivity of this important biological oxidant.

A nonheme iron(II) complex that models the redox cycle of lipoxygenase

Abstract. The air-stable complex [Fe(6-Me3-TPA)(O2CAr)]+ [1; 6-Me3-TPA=tris(6-methyl-2-pyridylmethyl)amine] has been synthesized as a model for the iron(II) site of lipoxygenase. This iron(II) complex reacts with 0.5 equiv ROOH to form a yellow species, which has been formulated as [FeIII(OH)(6-Me3-TPA)(O2CAr)]+ (2) by electrospray mass spectrometry. Addition of more ROOH converts 2 into a purple species, which is characterized by electrospray ionization mass spectrometry and resonance Raman spectroscopy as [FeIII(OOR)(6-Me3-TPA)(O2CAr)]+. The purple species is metastable and decomposes via Fe-O bond homolysis to regenerate the starting iron(II) complex. These metal-centered transformations parallel the changes observed for lipoxygenase in its reaction with its product hydroperoxide.

XAS characterization of end-on and side-on peroxoiron(iii) complexes of the neutral pentadentate N-donor ligand N-methyl-N, N′, N′-tris(2-pyridylmethyl)ethane-1,2-diamine

Peroxo intermediates are implicated in the catalytic cycles of iron enzymes involved in dioxygen metabolism. X-ray absorption spectroscopy has been used to gain insight into the iron coordination environments of the low-spin complex [Fe(III)(Me-TPEN)(eta(1)-OOH)](2+)(1) and the high-spin complex [Fe(III)(Me-TPEN)(eta(2)-O(2))](+)(2)(the neutral pentadentate N-donor ligand Me-TPEN =N-methyl-N,N,N-tris(2-pyridylmethyl)ethane-1,2-diamine) and obtain metrical parameters unavailable from X-ray crystallography. The complexes exhibit relatively large pre-edge peak areas of approximately 15 units, indicative of iron centers with significant distortions from centrosymmetry. These distortions result from the binding of peroxide, either end-on hydroperoxo for 1 (r(Fe-O)= 1.81A) or side-on peroxo for 2 (r(Fe-O)= 1.99 A). The XAS analyses of 1 strongly support a six-coordinate low-spin iron(III) center coordinated to five nitrogen atoms from Me-TPEN and one oxygen atom from an end-on hydroperoxide ligand. However, the XAS analyses of 2 are not conclusive: Me-TPEN can act either as a pentadentate ligand to form a seven-coordinate peroxo complex, which has precedence in the DFT geometry optimization of [Fe(III)(N4Py)(eta(2)-O(2))](+)(the neutral pentadentate N-donor ligand N4Py =N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), or as a tetradentate ligand with a dangling pyridylmethyl arm to form a six-coordinate peroxo complex, which is precedented by the crystal structure of [Fe(2)(III)(Me-TPEN)(2)(Cl)(2)(mu-O)](2+).

High conversion of olefins to cis-diols by non-heme iron catalysts and H2O2

Efficient and highly stereoselective oxidation of olefins to cis-diols as the major product is obtained by using biomimetic non-heme FeII catalysts in combination with H2O2.

Copper(I)-induced activation of dioxygen for the oxidation of organic substrates under mild conditions. An evaluation of ligand effects

Abstract Under the appropriate reaction conditions and stoichiometries the combination of a Cu(I) complex, t-BuOOH and molecular oxygen generates a catalyst that is capable of oxidizing alkanes, alkenes, alcohols and triphenyl phosphine under one atmosphere oxygen pressure and at room temperature. Particularly impressive is the performance of those catalysts over substrates containing allylic methylenes in terms of both reaction efficiencies and selectivities. For instance, for ethylbenzene the system 3 5 mM/t-BuOOH 10 mM; O2 1 atm/PhCH2Me 1 M in ac:py (1:2) as the solvent forms 57.7 mM acetophenone. Cyclohexene under similar reaction conditions yields 85.4 mM 2-cyclohexene-1-one and 3.5 mM 2-cyclohexene-1-ol.