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The steric properties of the tetradentate ligand influences the reactivities of the Fe(v)O units in a number of tautomeric Fe(v)(O)(OH) complexes.

Mononuclear MnII oxidation catalysts with aminopyridine-based ligands achieve high turnover-number (TON) enantioselective epoxidation of alkenes with H2O2. Structure reactivity relations indicate a dependence of enantioselectivity and maximum TON on the electronic effect of peripheral ligand substituents. Competing H2O2 disproportionation is reduced by carrying out reactions at low temperatures and with slow addition of H2O2, which improve TONs for alkene oxidation but mask the effect of substituents on turnover frequency (TOF). Here, in situ Raman spectroscopy provides the high time resolution needed to establish that the minimum TOFs are greater than 10 s-1 in the epoxidation of alkenes with the complexes [Mn(OTf)2(RPDP)] [where R = H (HPDP-Mn) and R = OMe (MeOPDP-Mn) and RPDP = N,N′-bis(2″-(4″-R-pyridylmethyl)-2,2′-bipyrrolidine)]. Simultaneous headspace monitoring by Raman spectroscopy reveals that H2O2 disproportionation proceeds concomitant with oxidation of the substrate and that the ratio of reactivity toward substrate oxidation and H2O2 disproportionation is ligand-dependent. Notably, the rates of substrate oxidation and H2O2 disproportionation both decrease over time under continuous addition of H2O2 due to progressive catalyst deactivation, which indicates that the same catalyst is responsible for both reactions. Electrochemistry, UV/vis absorption, and resonance Raman spectroscopy and spectroelectrochemistry establish that the MnII complexes undergo an increase in oxidation state within seconds of addition of H2O2 to form a dynamic mixture of MnIII and MnIV species, with the composition depending on temperature and the presence of alkene. However, it is the formation of these complexes (resting states), rather than ligand degradation, that is responsible for catalyst deactivation, especially at low temperatures, and hence, the intrinsic reactivity of the catalyst is greater than observed TOFs. These data show that interpretation of effects of ligand substituents on reaction efficiency (and conversion) with respect to the oxidant and maximum TONs needs to consider reversible deactivation of the catalyst and especially the relative importance of various reaction pathways.

The mechanism and the reactive species involved in the oxidation of alkenes, and alcohols with H2O2, catalysed by an in situ prepared mixture of a MnII salt, pyridine-2-carboxylic acid and a ketone is elucidated using substrate competition experiments, kinetic isotope effect (KIE) measurements, and atom tracking with 18O labelling. The data indicate that a single reactive species engages in the oxidation of both alkenes and alcohols. The primary KIE in the oxidation of benzyl alcohols is ca. 3.5 and shows the reactive species to be selective despite a zero order dependence on substrate concentration, and the high turnover frequencies (up to 30 s−1) observed. Selective 18O labelling identifies the origin of the oxygen atoms transferred to the substrate during oxidation, and is consistent with a highly reactive, e. g., [MnV(O)(OH)] or [MnV(O)2], species rather than an alkylperoxy or hydroperoxy species.

A manganese catalyst equipped with 18-benzo-6-crown ether receptors has been employed in the catalytic oxidation of tetradecane-1,14-diamine. Binding of the protonated amines results in selective (up to 92%) oxidation of the C6/C7 methylenic sites.

Two oxoiron(IV) isomers (R2a and R2b) of general formula [FeIV(O)(RPyNMe3)(CH3CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4IO4. The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R2a and R2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R2a reacts one order of magnitude faster than R2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.

The complex α-[Fe(mcp)(OTf)2] (mcp = N,N′-dimethyl-N,N′-bis(pyridin-2-ylmethyl)-cyclohexane-1,2-diamine and OTf = trifluoromethanesulfonate anion) was reported in 2011 by some of us as an active water oxidation (WO) catalyst in the presence of sacrificial oxidants. However, because chemical oxidants are likely to take part in the reaction mechanism, mechanistic electrochemical studies are critical in establishing to what extent previous studies with sacrificial reagents have actually been meaningful. In this study, the complex α-[Fe(mcp)(OTf)2] and its analogues were investigated electrochemically under both acidic and neutral conditions. All the systems under investigation proved to be electrochemically active toward the WO reaction, with no major differences in activity despite the structural changes. Our findings show that WO-catalyzed by mcp–iron complexes proceeds via homogeneous species, whereas the analogous manganese complex forms a heterogeneous deposit on the electrode surface. Mechanistic studies show that the reaction proceeds with a different rate-determining step (rds) than what was previously proposed in the presence of chemical oxidants. Moreover, the different kinetic isotope effect (KIE) values obtained electrochemically at pH 7 (KIE ∼ 10) and at pH 1 (KIE = 1) show that the reaction conditions have a remarkable effect on the rds and on the mechanism. We suggest a proton-coupled electron transfer (PCET) as the rds under neutral conditions, whereas at pH 1 the rds is most likely an electron transfer (ET) NWO Echo grant 717.014.008. PGC2018-101737-B-I00 and 2017 SGR 00264 grants

C-F bonds are one of the most inert functionalities. Nevertheless, some [Cu_2O_2]^2+ species are able to defluorinate-hydroxylate ortho-fluorophenolates in a chemoselective manner over other ortho-halophenolates. Albeit it is known that such reactivity is promoted by an electrophilic attack of a [Cu_2O_2]^2+ core over the arene ring, the crucial details of the mechanism that explain the chemo- and regioselectivity of the reaction remain unknown, and it has not being determined either if Cu^II_2(η_2:η_2-O_2) or Cu^III_2(μ-O)_2 species are responsible for the initial attack on the arene. Herein, we present a combined theoretical and experimental mechanistic study to unravel the origin of the chemoselectivity of the ortho-defluorination-hydroxylation of 2-halophenolates by the [Cu_2(O)_2(DBED)_2]2+ complex (DBED = N,N′-di-tert-butylethylenediamine). Our results show that the equilibria between (side-on)peroxo (P) and bis(μ-oxo) (O) isomers plays a key role in the mechanism, with the latter being the reactive species. Furthermore, on the basis of quantum-mechanical calculations, we were able to rationalize the chemoselective preference of the [Cu_2(O)_2(DBED)_2]^2+ catalyst for the C-F activation over C-Cl and C-H activations. This work was supported with funds from the Spanish government MICINN (PGC2018-098212-B-C22 to JML, PGC2018-101737-BI00 to M.C., CTQ2016-77989-P to A.C.), and the Generalitat de Catalunya (2017SGR39 to J.M.L, 2017 SGR 00264 and ICREA Academia to M.C. and A.C.). We thank the Spanish government for the predoctoral grant to P.B.-S. (FPU17/02058)

BACKGROUND AND OBJECTIVES The importance of hydrogen sulfide is increasingly recognized in the pathophysiology of obesity and type 2 diabetes in animal models. Very few studies have evaluated circulating sulfides in humans, with discrepant results. Here, we aimed to investigate serum sulfide levels according to obesity. SUBJECTS AND METHODS Serum sulfide levels were analyzed, using a selective fluorescent probe, in two independent cohorts [cross-sectionally in discovery (n = 139) and validation (n = 71) cohorts, and longitudinally in 82 participants from discovery cohort]. In the validation cohort, blood gene expression of enzymes contributing to H2S generation and consumption were also measured. RESULTS In the discovery cohort, serum sulfide concentration was significantly increased in subjects with morbid obesity at baseline and follow-up, and positively correlated with BMI and fat mass, but negatively with total cholesterol, haemoglobin, serum ferritin, iron and bilirubin after adjusting by age, gender and fat mass. Fat mass (β = 0.51, t = 3.67, p

The dynamic adaptability of tetragonal prismatic nanocapsule 18+ in the selective separation of fullerenes and endohedral metallofullerenes (EMFs) remains unexplored. Therefore, the essential molecular details of the fullerene recognition and binding process into the coordination capsule and the origins of fullerene selectivity remain elusive. In this work, the key steps of fullerene recognition and binding processes have been deciphered by designing a protocol which combines 1H-1H exchange spectroscopy (2D-EXSY) NMR experiments, long time-scale Molecular Dynamics (MD) and accelerated Molecular Dynamics (aMD) simulations, which are combined to completely reconstruct the spontaneous binding and unbinding pathways from nanosecond to second time-range. On one hand, binding (k'on) and unbinding (koff) rate constants were extracted from 1H-1H exchange spectroscopy (EXSY) NMR experiments for both C60 and C70. On the other hand, MD and aMD allowed monitoring the molecular basis of the encapsulation and guest competition processes at a very early stage under nonequilibrium conditions. The receptor capsule displays dynamical adaptability features similar to those observed in the process of biomolecular recognition in proteins. In addition, the encapsulation of bis-aza[60]fullerene (C59N)2 within a supramolecular coordination capsule has been studied for the first time, showcasing the pros and cons of the dumbbell-shaped guest in the dynamics of the encapsulation process and in the stability of the final bound adduct. The powerful combination of NMR, MD, and aMD methodologies allows to obtain a precise picture of the subtle events directing the encapsulation and is thus a predictive tool for understanding host-guest encapsulation and interactions in numerous supramolecular systems.

Predictability is a key requirement to encompass late-stage C-H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp3 )-H oxidation, as it requires distinguishing a specific C-H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C-H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host-guest adduct by NMR analysis. These analyses indicate which remote C-H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late-stage C(sp3 )-H oxidation of amino-steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.

The C(sp

Reactions that enable selective functionalization of strong aliphatic C-H bonds open new synthetic paths to rapidly increase molecular complexity and expand chemical space. Particularly valuable are reactions where site-selectivity can be directed toward a specific C-H bond by catalyst control. Herein we describe the catalytic site- and stereoselective γ-lactonization of unactivated primary C-H bonds in carboxylic acid substrates. The system relies on a chiral Mn catalyst that activates aqueous hydrogen peroxide to promote intramolecular lactonization under mild conditions, via carboxylate binding to the metal center. The system exhibits high site-selectivity and enables the oxidation of unactivated primary γ-C-H bonds even in the presence of intrinsically weaker and a priori more reactive secondary and tertiary ones at α- and β-carbons. With substrates bearing nonequivalent γ-C-H bonds, the factors governing site-selectivity have been uncovered. Most remarkably, by manipulating the absolute chirality of the catalyst, γ-lactonization at methyl groups in gem-dimethyl structural units of rigid cyclic and bicyclic carboxylic acids can be achieved with unprecedented levels of diastereoselectivity. Such control has been successfully exploited in the late-stage lactonization of natural products such as camphoric, camphanic, ketopinic, and isoketopinic acids. DFT analysis points toward a rebound type mechanism initiated by intramolecular 1,7-HAT from a primary γ-C-H bond of the bound substrate to a highly reactive MnIV-oxyl intermediate, to deliver a carbon radical that rapidly lactonizes through carboxylate transfer. Intramolecular kinetic deuterium isotope effect and 18O labeling experiments provide strong support to this mechanistic picture This work was supported by the Spanish Ministry of Science, Innovation, and Universities (PGC2018-101737-B-I00 to M.C., PGC2018-098212-B-C22 to J.M.L., IJC2020-046115-I to A.C.; and PhD grants FPU16/04231 to L.V., FPU17/02058 to P.B.-S., and PRE2019-090149 to A.P.), the University of Rome “Tor Vergata” (Project E84I20000250005), the European Research Council, (AdvG 883922 to M.C.), and Generalitat de Catalunya (ICREA Academia Award and 2017-SGR00264 to M.C. and X.R., and 2017SGR39 to J.M.L.)

Precise delivery of a proton plays a key role in O2 activation at iron oxygenases, enabling the crucial O−O cleavage step that generates the oxidizing high-valent metal–oxo species. Such a proton is delivered by acidic residues that may either directly bind the iron center or lie in its second coordination sphere. Herein, a supramolecular strategy for enzyme-like H2O2 activation at a biologically inspired manganese catalyst, with a nearly stoichiometric amount (1–1.5 equiv) of a carboxylic acid is disclosed. Key for this strategy is the incorporation of an α,ω-amino acid in the second coordination sphere of a chiral catalyst via remote ammonium-crown ether recognition. The properly positioned carboxylic acid function enables effective activation of hydrogen peroxide, leading to catalytic asymmetric epoxidation. Modulation of both amino acid and catalyst structure can tune the efficiency and the enantioselectivity of the reaction, and a study on the oxidative degradation pathway of the system is presented We acknowledge STR of UdG for experimental support.This work was supportedby Spanish Ministry of Science,Innovation and Universities (PGC2018-101737-B-I00 to M.C., J.d.C. grant FJCI-2016-30243 to G.O.and PhD grant FPU16/04231to L.V.) and Generalitat de Catalunya (ICREA Academia Awardto M.C.and 2014SGR 862) Open Access funding provided thanks to the CRUE-CSIC agreement with Wiley

Site-selective and product chemoselective aliphatic C–H bond oxidation of 1,2-diols and of polyhydroxylated substrates using iron and manganese catalysts and hydrogen peroxide as terminal oxidant i...

An iron complex bearing the facially capping tridentate 1,4,7-triazacyclononane ligand mimics structural and functional features of alpha-ketoglutarate (α-KG) dependent enzymes, and engages in enzyme-like catalytic O2 activation coupled to α-ketoacid decarboxylation, oxygenating sulfides. This system constitutes a rare case of non-enzymatic catalytic O2 activation, cycling between FeII and FeIV(O).

We report and analyze chemoselectivity in the gas phase reactions of cycloalkenes (cyclohexene, cycloheptene, cis-cyclooctene, 1,4-cyclohexadiene) with a non-heme iron(IV)-oxo complex [(PyTACN)Fe(O)(Cl)]+, which models the active species in iron-dependent halogenases. Unlike in the halogenases, we did not observe any chlorination of the substrate. However, we observed two other reaction pathways: allylic hydrogen atom transfer (HAT) and alkene epoxidation. The HAT is clearly preferred in the case of 1,4-cyclohexadiene, both pathways have comparable reaction rates in reaction with cyclohexene, and epoxidation is strongly favored in reactions with cycloheptene and cis-cyclooctene. This preference for epoxidation differs from the reactivity of iron(IV)-oxo complexes in the condensed phase, where HAT usually prevails. To understand the observed selectivity, we analyze effects of the substrate, spin state, and solvation. Our DFT and CASPT2 calculations suggest that all the reactions occur on the quintet potential energy surface. The DFT-calculated energies of the transition states for the epoxidation and hydroxylation pathways explain the observed chemoselectivity. The SMD implicit solvation model predicts the relative increase of the epoxidation barriers with solvent polarity, which explains the clear preference of HAT in the condensed phase. Electronic supplementary material The online version of this article (10.1007/s13361-019-02251-1) contains supplementary material, which is available to authorized users.

International audience; Oxoiron(IV) complexes bearing tetradentate ligands have been extensively studied as models for the active oxidants in non-heme iron-dependent enzymes. These species are commonly generated by oxidation of their ferrous precursors. The mechanisms of these reactions have seldom been investigated. In this work, the reaction kinetics of complexes [Fe-II(CH3CN)(2)L](SbF6)(2) ([1](SbF6)(2) and [2](SbF6)(2)) and [Fe-II(CF3SO3)(2)L] ([1](OTf)(2) and [2](OTf)(2) (1, L=(Me,H)Pytacn; 2, L=(nP,H)Pytacn; (R,R ')Pytacn=1-[(6-R '-2-pyridyl)methyl]-4,7- di-R-1,4,7-triazacyclononane) with Bu4NIO4 to form the corresponding [Fe-IV(O)(CH3CN)L](2+) (3, L=(Me,H)Pytacn; 4, L=(nP,H)Pytacn) species was studied in acetonitrile/acetone at low temperatures. The reactions occur in a single kinetic step with activation parameters independent of the nature of the anion and similar to those obtained for the substitution reaction with Cl- as entering ligand, which indicates that formation of [Fe-IV(O)(CH3CN)L](2+) is kinetically controlled by substitution in the starting complex to form [Fe-II(IO4)(CH3CN)L](+) intermediates that are converted rapidly to oxo complexes 3 and 4. The kinetics of the reaction is strongly dependent on the spin state of the starting complex. A detailed analysis of the magnetic susceptibility and kinetic data for the triflate complexes reveals that the experimental values of the activation parameters for both complexes are the result of partial compensation of the contributions from the thermodynamic parameters for the spin-crossover equilibrium and the activation parameters for substitution. The observation of these opposite and compensating effects by modifying the steric hindrance at the ligand illustrates so far unconsidered factors governing the mechanism of oxygen atom transfer leading to high-valent iron oxo species.

The complex α-[Fe(mcp)(OTf)2] (mcp = N,N′-dimethyl-N,N′-bis(pyridin-2-ylmethyl)-cyclohexane-1,2-diamine and OTf = trifluoromethanesulfonate anion) was reported in 2011 by some of us as an active water oxidation (WO) catalyst in the presence of sacrificial oxidants. However, because chemical oxidants are likely to take part in the reaction mechanism, mechanistic electrochemical studies are critical in establishing to what extent previous studies with sacrificial reagents have actually been meaningful. In this study, the complex α-[Fe(mcp)(OTf)2] and its analogues were investigated electrochemically under both acidic and neutral conditions. All the systems under investigation proved to be electrochemically active toward the WO reaction, with no major differences in activity despite the structural changes. Our findings show that WO-catalyzed by mcp–iron complexes proceeds via homogeneous species, whereas the analogous manganese complex forms a heterogeneous deposit on the electrode surface. Mechanistic studies show that the reaction proceeds with a different rate-determining step (rds) than what was previously proposed in the presence of chemical oxidants. Moreover, the different kinetic isotope effect (KIE) values obtained electrochemically at pH 7 (KIE ∼ 10) and at pH 1 (KIE = 1) show that the reaction conditions have a remarkable effect on the rds and on the mechanism. We suggest a proton-coupled electron transfer (PCET) as the rds under neutral conditions, whereas at pH 1 the rds is most likely an electron transfer (ET).

Oxoiron(IV) complexes bearing tetradentate ligands have been extensively studied as models for the active oxidants in non-heme iron-dependent enzymes. These species are commonly generated by oxidation of their ferrous precursors. The mechanisms of these reactions have seldom been investigated. In this work, the reaction kinetics of complexes [Fe

An iron complex bearing the facially capping tridentate 1,4,7-triazacyclononane ligand mimics structural and functional features of alpha-ketoglutarate (α-KG) dependent enzymes, and engages in enzyme-like catalytic O2 activation coupled to α-ketoacid decarboxylation, oxygenating sulfides. This system constitutes a rare case of non-enzymatic catalytic O2 activation, cycling between FeII and FeIV(O).

The dynamic adaptability of tetragonal prismatic nanocapsule

α-Amino acids represent a valuable class of natural products employed as building blocks in biological and chemical synthesis. Because of the limited number of natural amino acids available, and of their widespread application in proteomics, diagnosis, drug delivery and catalysis, there is an increasing demand for the development of procedures for the preparation of modified analogues. Herein, we show that the use of bioinspired manganese catalysts and H 2 O 2 under mild conditions, provides access to modified α-amino acids via γ-C-H bond lactonization. The system can efficiently target 1o, 2o and 3o γ-C-H bonds of α-substituted and achiral α,α-disubstituted α-amino acids with outstanding site-selectivity, good to excellent diastereoselectivity and (where applicable) enantioselectivity. This methodology may be considered alternative to well-established organometallic procedures.

FeV(O)(OH) species have long been proposed to play a key role in a wide range of biomimetic and enzymatic oxidations, including as intermediates in arene dihydroxylation catalyzed by Rieske oxygenases. However, the inability to accumulate these intermediates in solution has thus far prevented their spectroscopic and chemical characterization. Thus, we use gas-phase ion spectroscopy and reactivity analysis to characterize the highly reactive [FeV(O)(OH)(5tips3tpa)]2+ (32+) complex. The results show that 32+ hydroxylates C–H bonds via a rebound mechanism involving two different ligands at the Fe center and dihydroxylates olefins and arenes. Hence, this study provides a direct evidence of FeV(O)(OH) species in non-heme iron catalysis. Furthermore, the reactivity of 32+ accounts for the unique behavior of Rieske oxygenases. The use of gas-phase ion characterization allows us to address issues related to highly reactive intermediates that other methods are unable to solve in the context of catalysis and enzymology., FeV(O)(OH) species have long been thought to play a role in a range of enzymatic oxidations, but their characterization has remained elusive. Here, using gas-phase ion spectroscopy, the authors characterize an FeV(O)(OH) species and find that its reactivity mimics that of Rieske oxygenases.

A novel naphthalene-based 5·(BArF) 8 capsule allows for the size-selective inclusion of C 60 from fullerene mixtures. Its size selectivity towards C 60 has been rationalized by its dynamic adaptability in solution that has been investigated by molecular dynamics. Additionally, 5·(BArF) 8 encapsulates C 60 -derivatives such as C 60 -PCBM and N-methylpyrrolidine-C 60 . The latter can be separated from C 60 since 5·(BArF) 8 displays distinct affinity for them., This work was supported by MINECO-Spain (CTQ2016-77989-P to X. R., CTQ2015-70795-P to M. C., MAT2015-65354-C2-1-R to D. M. and I. I., 2017 SGR 264 to X. R., and 2014SGR80 to D. M.), the CERCA Programme/Generalitat de Catalunya, ICREA-Academia (X. R. and M. C.), the Ramon Areces Foundation (M. G.-B.) and the Severo Ochoa Center of Excellence Program (ICN2, Grant SEV-2017-0706).

The synthesis and solution characterization of the mononuclear copper(I) complex [Cu I (PyNMe 3 )(CH 3 CN)] + ( 1 ) is described. This compound presents a C s symmetric architecture as ascertained by NMR spectroscopy and corroborated by DFT calculations. The reactivity of 1 towards O 2 in a CH 3 CN:THF 1:19 mixture at −100 °C was monitored by UV–vis spectroscopy, which evidenced the formation of a new species ( 2 ) with a highly intense absorption at 353 nm (e > 17200 M −1 cm −1 ) that was not stable even at this low temperature (t 1/2 = 6 min at −100 °C). This spectroscopic signature is characteristic of μ-η 2 :η 2 -peroxodicopper(II) complexes, which typically exhibit one single intense absorption between 340 and 380 nm. Despite the fact that such species are involved in the catalytic cycle of tyrosinase, a copper-based enzyme that ortho -hydroxylates phenols, attempts to hydroxylate phenolates by 2 turned out to be unsuccessful. Most probably, the rigid macrocyclic tetradentate architecture of the PyNMe 3 ligand hinders simultaneous peroxide and phenolate coordination in the same copper center, a necessary step prior to the ortho -hydroxylation of this substrate.

Aliphatic C–H bond functionalization is at the frontline of research because it can provide straightforward access to simplified and cost-effective synthetic procedures. A number of these methodologies are based on hydrogen atom transfer (HAT), which, as a consequence of the inert character of C–H bonds, often represents the most challenging step of the overall process. Because the majority of organic molecules contain multiple nonequivalent C–H bonds that display similar chemical properties, differentiating between these bonds with high levels of selectivity represents one of the most challenging issues. Clarification of the factors that govern the relative reactivity of C–H bonds toward HAT reagents is thus of primary importance in order to develop selective functionalization procedures.In this Account we describe, through the combination of kinetic studies employing a genuine HAT reagent such as the cumyloxyl radical, along with oxidations performed with H2O2 and iron or manganese catalysts, our contri...

Herein, we disclose the application of green solvents in a biologically inspired oxidation reaction. In a mixture of propylene carbonate and ethyl acetate, iron catalyzed syn-dihydroxylation of olefins with aqueous hydrogen peroxide proceeds in short reaction times with excellent yields and chemoselectivity. The current report showcases the suitability of this sustainable media to this class of important reactions.

The reaction of [(PyNMe3)FeII(CF3SO3)2], 1, with excess peracetic acid at −40 °C generates a highly reactive intermediate, 2b(PAA), that has the fastest rate to date for oxidizing cyclohexane by a nonheme iron species. It exhibits an intense 490 nm chromophore associated with an S = 1/2 EPR signal having g-values at 2.07, 2.01, and 1.94. This species was shown to be in a fast equilibrium with a second S = 1/2 species, 2a(PAA), assigned to a low-spin acylperoxoiron(III) center. Unfortunately, contaminants accompanying the 2(PAA) samples prevented determination of the iron oxidation state by Mossbauer spectroscopy. Use of MeO-PyNMe3 (an electron-enriched version of PyNMe3) and cyclohexyl peroxycarboxylic acid as oxidant affords intermediate 3b(CPCA) with a Mossbauer isomer shift δ = −0.08 mm/s that indicates an iron(V) oxidation state. Analysis of the Mossbauer and EPR spectra, combined with DFT studies, demonstrates that the electronic ground state of 3b(CPCA) is best described as a quantum mechanical mixt...

A novel hydroperoxoiron(III) species [Fe III (OOH)(MeCN)(PyNMe 3 )] 2+ (3) has been generated by reaction of its ferrous precursor [Fe II (CF 3 SO 3 ) 2 (PyNMe 3 )] (1) with hydrogen peroxide at low temperatures. This species has been characterized by several spectroscopic techniques and cryospray mass spectrometry. Similar to most of the previously described low-spin hydroperoxoiron(III) compounds, 3 behaves as a sluggish oxidant and it is not kinetically competent for breaking weak C−H bonds. However, triflic acid addition to 3 causes its transformation into a much more reactive compound towards organic substrates that is capable of oxidizing unactivated C−H bonds with high stereospecificity. Stopped-flow kinetic analyses and theoretical studies provide a rationale for the observed chemistry, a triflic-acid-assisted heterolytic cleavage of the O−O bond to form a putative strongly oxidizing oxoiron(V) species. This mechanism is reminiscent to that observed in heme systems, where protonation of the hydroperoxo intermediate leads to the formation of the high-valent [(Porph . )Fe IV (O)] (Compound I) Financial support for this work was provided by the European Commission (2011-CIG-303522 to A.C., 675020-MSCA-ITN-2015-ETN to M.C.), the Spanish Ministry of Science (CTQ2015-70795-P to M.C., CTQ2016-77989-P to A.C., CTQ2014-52525-P to J.M.L., CTQ2015-65707-C2-2-P to M.G.B., and CSD2010-00065 to M.C and M.G.B.) and Generalitat de Catalunya (ICREA Academia Award to M.C. and 2014 SGR 862). The Spanish Ministry of Science is also acknowledged for a Ram n y Cajal contract to A.C. (RYC-2011–08683). The work conducted at the University of Minnesota has been supported by the US National Science Foundation (grant CHE1665391 to L.Q.). XAS data was collected at the SOLEIL synchrotron SAMBA beamline (proposal 20150413)

A kinetic study on the hydrogen atom transfer (HAT) reactions from the aliphatic C–H bonds of a series of 1-Z-pentyl, 1-Z-propyl, and Z-cyclohexyl derivatives and of a series of N-alkylamides and N-alkylphthalimides to the electrophilic cumyloxyl radical (CumO•) has been carried out. With 1-pentyl and 1-propyl derivatives, α-CH2 activation toward CumO• is observed for Z = Ph, OH, NH2, and NHAc, as evidenced by an increase in kH as compared to the unsubstituted alkane substrate. A decrease in kH has been instead measured for Z = OAc, NPhth, CO2Me, Cl, Br, and CN, indicative of α-CH2 deactivation with HAT that predominantly occurs from the most remote methylenic site. With cyclohexyl derivatives, α-CH activation is only observed for Z = OH and NH2, indicative of torsional effects as an important contributor in governing the functionalization selectivity of monosubstituted cyclohexanes. In the reactions of N-alkylamides and N-alkylphthalimides with CumO•, the reactivity and selectivity patterns parallel thos...

Site-selective C-H functionalization of aliphatic alkyl chains is a longstanding challenge in oxidation catalysis, given the comparable relative reactivity of the different methylenes. A supramolecular, bioinspired approach is described to address this challenge. A Mn complex able to catalyze C(sp3 )-H hydroxylation with H2 O2 is equipped with 18-benzocrown-6 ether receptors that bind ammonium substrates via hydrogen bonding. Reversible pre-association of protonated primary aliphatic amines with the crown ether selectively exposes remote positions (C8 and C9) to the oxidizing unit, resulting in a site-selective oxidation. Remarkably, such control of selectivity retains its efficiency for a whole series of linear amines, overriding the intrinsic reactivity of C-H bonds, no matter the chain length.

We report the generation of iron(V) nitride complexes, which are targets of biomimetic chemistry. Temperature-dependent ion spectroscopy shows that this reaction is governed by the spin state population of their iron(III) azide precursors and can be tuned by temperature. The complex [(MePy2TACN)Fe(N3)]2+ exists as a mixture of sextet and doublet spin states at 300 K, whereas only the doublet state is populated at 3 K. Photofragmentation of the sextet state complex leads to the reduction of the iron centre. The doublet state complex photodissociates to the desired iron(V) nitride complex. To generalize these findings, we show results for complexes with cyclam-based ligands.

Site selective C–H oxidation of N-alkylamides and phthalimides with aqueous hydrogen peroxide catalyzed by manganese complexes is described. These catalysts are shown to exhibit substantially improved performance in product yields and substrate scope in comparison with their iron counterparts. The nature of the amide and imide group and of the N-alkyl moiety are shown to be effective tools in order to finely tune site selectivity between proximal (adjacent to the nitrogen) and remote C–H bonds on the basis of steric, electronic, and stereoelectronic effects. Moreover, formation of the α-hydroxyalkyl product in good yield and with excellent product chemoselectivity was observed in the reactions of the pivalamide and acetamide derivatives bearing an α-CH2 group, pointing again toward an important role played by stereoelectronic effects and supporting the hypothesis that these oxidations proceed via hydrogen atom transfer (HAT) to a high-valent manganese–oxo species. Good product yields and mass balances are...

Iron complexes with chiral tetradentate ligands based on the pdp scaffold (pdp = N,N′-bis(2-pyridylmethyl)-2,2′-bipyrrolidine) are efficient and versatile catalysts for the highly enantioselective epoxidation of a wide range of olefins. The nature of the species responsible for oxygen atom transfer to the olefin in these reactions is under debate. In order to investigate this question, the enantioselectivity of the epoxidation reaction has been used as a mechanistic probe. The enantioselectivities obtained under different reaction conditions for two iron catalysts (S,S)-[Fe(CF3SO3)2(Me2Npdp)] ((S,S)Me2N1Fe) and (S,S)-[Fe(CF3SO3)2(dMMpdp)] ((S,S)dMM1Fe) have been analyzed. Reactions were performed with a series of peracids, and enantioselectivities of these reactions were compared with those obtained by combining peroxides and carboxylic acids. This analysis provides conclusive experimental evidence that the same oxidant is responsible for the asymmetric epoxidation reaction in both scenarios. The study al...

C–H bond activation mediated by oxo-iron (IV) species represents the key step of many heme and nonheme O2-activating enzymes. Of crucial interest is the effect of spin state of the FeIV(O) unit. Here we report the C–H activation kinetics and corresponding theoretical investigations of an exclusive tetracarbene ligated oxo-iron(IV) complex, [LNHCFeIV(O)(MeCN)]2+ (1). Kinetic traces using substrates with bond dissociation energies (BDEs) up to 80 kcal mol–1 show pseudo-first-order behavior and large but temperature-dependent kinetic isotope effects (KIE 32 at −40 °C). When compared with a topologically related oxo-iron(IV) complex bearing an equatorial N-donor ligand, [LTMCFeIV(O) (MeCN)]2+ (A), the tetracarbene complex 1 is significantly more reactive with second order rate constants k′2 that are 2–3 orders of magnitude higher. UV–vis experiments in tandem with cryospray mass spectrometry evidence that the reaction occurs via formation of a hydroxo-iron(III) complex (4) after the initial H atom transfer (H...

A nonheme iron catalyst catalyzed stereoselective oxidation of alkanes with H2O2 with remarkable efficiency and exhibiting an unprecedented high incorporation of water into the oxidized products. The present results challenge the canonical description of oxygenases, the standard oxo-hydroxo tautomerism that applies to heme systems and serves as a precedent for alternative pathways for the oxidation of hydrocarbons at nonheme iron oxygenases Financial support from MCYT of Spain (CTQ2006–05367 to MC) and from US-DOE (DE-FG02-03ER15455 to LQ) is gratefully acknowledged

Recognizing Nature’s unique ability to perform challenging oxygenation reactions with exquisite selectivity parameters at iron dependent oxygenases, chemists have long sought to understand and mimi...

Summary Isomer-pure poly-functionalized fullerenes are required to boost the development of fullerene chemistry in all fields. On a general basis, multi-adduct mixtures with uncontrolled regioselectivity are obtained, and the use of chromatographic purification is prohibitively costly and time consuming, especially in the production of solar cells. Single-isomer poly-functionalized fullerenes are only accessible via stoichiometric, multistep paths entailing protecting-unprotecting sequences. Herein, a nanocapsule is used as a supramolecular tetragonal prismatic mask to exert full control on the reactivity and the equatorial regioselectivity of Bingel-Hirsch cyclopropanation reactions of a confined C60 guest. Thus, equatorial bis-, tris-, and tetrakis-C60 homo-adducts are exclusively obtained in a stepwise manner. Furthermore, isomer-pure equatorial hetero-tetrakis-adducts or hetero-Th-hexakis-adducts are synthesized at will in one-pot synthesis for the first time. This work provides a synthetically valuable path to produce a plethora of new pure-isomer poly-functionalized C60-based compounds as candidates for testing in solar cell devices and biomedical applications. Video Abstract Download : Download video (34MB)