Does Hydrogen‐Bonding Donation to Manganese(IV)–Oxo and Iron(IV)–Oxo Oxidants Affect the Oxygen‐Atom Transfer Ability? A Computational Study

Iron(IV)–oxo intermediates are involved in oxidations catalyzed by heme and nonheme iron enzymes, including the cytochromes P450. At the distal site of the heme in P450 Compound I (Fe^IV–oxo bound to porphyrin radical), the oxo group is involved in several hydrogen‐bonding interactions with the protein, but their role in catalysis is currently unknown. In this work, we investigate the effects of hydrogen bonding on the reactivity of high‐valent metal–oxo moiety in a nonheme iron biomimetic model complex with trigonal bipyramidal symmetry that has three hydrogen‐bond donors directed toward a metal(IV)–oxo group. We show these interactions lower the oxidative power of the oxidant in reactions with dehydroanthracene and cyclohexadiene dramatically as they decrease the strength of the O? H bond (BDE_OH) in the resulting metal(III)–hydroxo complex. Furthermore, the distal hydrogen‐bonding effects cause stereochemical repulsions with the approaching substrate and force a sideways attack rather than a more favorable attack from the top. The calculations, therefore, give important new insights into distal hydrogen bonding, and show that in biomimetic, and, by extension, enzymatic systems, the hydrogen bond may be important for proton‐relay mechanisms involved in the formation of the metal–oxo intermediates, but the enzyme pays the price for this by reduced hydrogen atom abstraction ability of the intermediate. Indeed, in nonheme iron enzymes, where no proton relay takes place, there generally is no donating hydrogen bond to the iron(IV)–oxo moiety.     

Generating CuII–Oxyl/CuIII–Oxo Species from CuI–α‐Ketocarboxylate Complexes and O2: In Silico Studies on Ligand Effects and C?H‐Activation Reactivity

Theoretically speaking : The mechanistic details associated with the generation and reaction of [CuO]⁺ species from Cu^I–α‐ketocarboxylate complexes, especially with respect to modifications of the ligand supporting the copper center, were investigated (see scheme). Theoretical models were used to characterize the electronic structures of different [CuO]⁺ species and their reactivity in C? H activation and O‐atom transfer reactions.

     

Dioxygen Reactivity of Biomimetic Iron–Catecholate and Iron–o‐Aminophenolate Complexes of a Tris(2‐pyridylthio)methanido Ligand: Aromatic C?C Bond Cleavage of Catecholate versus o‐Iminobenzosemiquinonate Radical Formation

An iron(III)–catecholate complex [L¹Fe^III(DBC)] ( 2 ) and an iron(II)–o‐aminophenolate complex [L¹Fe^II(HAP)] ( 3 ; where L¹=tris(2‐pyridylthio)methanido anion, DBC=dianionic 3,5‐di‐tert‐butylcatecholate, and HAP=monoanionic 4,6‐di‐tert‐butyl‐2‐aminophenolate) have been synthesised from an iron(II)–acetonitrile complex [L¹Fe^II(CH₃CN)₂](ClO₄) ( 1 ). Complex 2 reacts with dioxygen to oxidatively cleave the aromatic C? C bond of DBC giving rise to selective extradiol cleavage products. Controlled chemical or electrochemical oxidation of 2 , on the other hand, forms an iron(III)–semiquinone radical complex [L¹Fe^III(SQ)](PF₆) ( 2^ox‐PF₆ ; SQ=3,5‐di‐tert‐butylsemiquinonate). The iron(II)–o‐aminophenolate complex ( 3 ) reacts with dioxygen to afford an iron(III)–o‐iminosemiquinonato radical complex [L¹Fe^III(ISQ)](ClO₄) ( 3^ox‐ClO₄ ; ISQ=4,6‐di‐tert‐butyl‐o‐iminobenzosemiquinonato radical) via an iron(III)–o‐amidophenolate intermediate species. Structural characterisations of 1 , 2 , 2^ox and 3^ox reveal the presence of a strong iron? carbon bonding interaction in all the complexes. The bond parameters of 2^ox and 3^ox clearly establish the radical nature of catecholate‐ and o‐aminophenolate‐derived ligand, respectively. The effect of iron? carbon bonding interaction on the dioxygen reactivity of biomimetic iron–catecholate and iron–o‐aminophenolate complexes is discussed.     

Olefin cis‐Dihydroxylation and Aliphatic C?H Bond Oxygenation by a Dioxygen‐Derived Electrophilic Iron–Oxygen Oxidant

Many iron‐containing enzymes involve metal–oxygen oxidants to carry out O₂‐dependent transformation reactions. However, the selective oxidation of C H and CC bonds by biomimetic complexes using O₂ remains a major challenge in bioinspired catalysis. The reactivity of iron–oxygen oxidants generated from an Fe^II–benzilate complex of a facial N₃ ligand were thus investigated. The complex reacted with O₂ to form a nucleophilic oxidant, whereas an electrophilic oxidant, intercepted by external substrates, was generated in the presence of a Lewis acid. Based on the mechanistic studies, a nucleophilic Fe^II–hydroperoxo species is proposed to form from the benzilate complex, which undergoes heterolytic O O bond cleavage in the presence of a Lewis acid to generate an Fe^IV–oxo–hydroxo oxidant. The electrophilic iron–oxygen oxidant selectively oxidizes sulfides to sulfoxides, alkenes to cis‐diols, and it hydroxylates the C H bonds of alkanes, including that of cyclohexane.     

Electronic Tuning of Iron–Oxo‐Mediated C?H Activation: Effect of Electron‐Donating Ligand on Selectivity

We have reported previously that an iron(III) complex supported by an anionic pentadentate monoamido ligand, dpaq^H (dpaq^H=2‐[bis(pyridin‐2‐ylmethyl)]amino‐N‐quinolin‐8‐yl‐acetamido), promotes selective C? H hydroxylation with H₂O₂ with high regioselectivity. Herein, we report on the preparation of Fe^III–dpaq derivatives that have a series of substituent groups at the 5‐position of a quinoline moiety in the parent ligand dpaq^H (dpaq^R, R: OMe, H, Cl, and NO₂), and examine them with respect to their catalytic activity in C? H hydroxylation with H₂O₂. As the substituent group becomes more electron‐withdrawing, both the selectivity and the turnover number increase, but the selectivity of epoxidation shows the opposite trend.     

Iron‐Catalyzed C?H Bond Activation for the ortho‐Arylation of Aryl Pyridines and Imines with Grignard Reagents

Direct arylation of the ortho‐C? H bond of an aryl pyridine or an aryl imine with an aryl Grignard reagent has been achieved by using an iron‐diamine catalyst and a dichloroalkane as an oxidant in a short reaction time (e.g., 5 min) under mild conditions (0 °C). The use of an aromatic co‐solvent, such as chlorobenzene and benzene, and slow addition of the Grignard reagent are essential for the high efficiency of the reaction. The present arylation reaction has distinct merits over the previously developed reaction that used an arylzinc reagent, such as its reaction rate and atom economy. Selective C? H bond activation occurs in the presence of a leaving group, such as a tosyloxy, chloro, and bromo group. Studies on a stoichiometric reaction and kinetic isotope effects shed light on the reaction intermediate and the C? H bond‐activation step.     

Where Is the Limit of Highly Fluorinated High‐Oxidation‐State Osmium Species?

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.     

Diketopyrrolopyrrole?Thiophene‐Based Acceptor–Donor–Acceptor Conjugated Materials for High‐Performance Field‐Effect Transistors

We report the synthesis, morphology, and field‐effect‐transistor (FET) characteristics of new acceptor–donor–acceptor conjugated materials that consist of diketopyrrolopyrrole (DPP) acceptor groups and one of four different thiophene moieties, that is, dithiophene (2T), thieno[3,2‐b]‐thiophene (TT), dithieno[3,2‐b:2′,3′‐d]‐thiophene (DTT), and 5,5′′′‐di‐(2‐ethylhexyl)‐[2,3′;5′,2′′;4′′,2′′′]quaterthiophene (4T). The optical band gaps of the as‐prepared materials are smaller than 1.7 eV, which is attributed to the strong intramolecular charge transfer and the backbone coplanarity of the thiophene moieties. The order of both crystallinity and FET mobility (×10^?2–×10^?4 cm² V^?1 s^?1) is TT2DPP > 4T2DPP > 2T2DPP >DTT2DP, which differ in the structure of the π‐conjugated cores and core symmetry. Well‐ordered intermolecular chain packing was confirmed by the GIXD and AFM results. In particular, the FET hole mobility of TT2DPP was further improved to 0.1 cm² V^?1 s^?1, which was attributed to the well‐interconnected structure through solution‐shearing. These experimental results suggest the potential applications of the new DPP? thiophene? DPP conjugated materials for organic electronic devices.     

Resonance‐Assisted Intramolecular Chalcogen–Chalcogen Interactions?

High-level B3LYP/6-311+G(3df,2p) density functional calculations have been carried out for a series of saturated chalcogenoaldehydes: CH(X)-CH(2)-CH(2)YH (X, Y=O, S, Se, Te). Our results indicate that in CH(X)-CH(2)-CH(2)YH (X=Y=O, S, Se) the X-H...X intramolecular hydrogen bond (IHB) competes in strength with the X...XH chalcogen-chalcogen interaction, while the opposite is found for the corresponding tellurium-containing analogues. For those derivatives in which X does not equal Y, X being the more electronegative atom, the situation is more complicated due to the existence of two non-equivalent X-H and Y-H tautomers. The Y-H tautomer is found to be lower in energy than the X-H tautomer, independently of the nature of X and Y. For X=O, S, Se and Y=S, Se the most stable conformer b is the one exhibiting a Y-H...X IHB. Conversely when Y=Te, the chelated conformer d, stabilized through a X...YH chalcogen-chalcogen interaction is the global minimum of the potential energy surface. Systematically the IHB and the chalcogen-chalcogen interactions observed for saturated compounds are much weaker than those found for their unsaturated analogues. This result implies that the nonbonding interactions involving chalcogen atoms, mainly Se and Te, are not always strongly stabilizing. This conclusion is in agreement with the fact that intermolecular interactions between Se and Te containing systems with bases bearing dative groups are very weak. We have also shown that these interactions are enhanced for unsaturated compounds, through an increase of the charge delocalization within the system, in a mechanism rather similar to the so call Resonance Assisted Hydrogen Bonds (RAHB). The chalcogen-chalcogen interactions will be also large, due to the enhancement of the X-->Y dative bond, if the molecular environment forces the interacting atoms X and Y to be close each other.     

Intramolecular Methylacridan–Methylacridinium Complexes with a Phenanthrene‐4,5‐diyl or Related Skeleton: Geometry–Property Relationships in Isolable C?H Bridged Carbocations

Bridging the gap : Snapshots of 1,6‐H‐shift precursors indicate that a narrower C? H???C⁺ separation (D in the ORTEP diagram) in the title complexes induces faster degenerate rearrangement of 1 ⁺. A contact distance of less than 2.7 Å is necessary to realize the organic three‐center two‐electron bond of [C? H? C]⁺, as indicated by extrapolation of the X‐ray data.

     

Direct Synthesis of 1,4‐Diols from Alkenes by Iron‐Catalyzed Aerobic Hydration and C?H Hydroxylation

Various 1,4‐diols are easily accessible from alkenes through iron‐catalyzed aerobic hydration. The reaction system consists of a user‐friendly iron phthalocyanine complex, sodium borohydride, and molecular oxygen. Furthermore, the effect of additional ligands on the iron complex was examined for a model reaction. The second hydroxy group is installed by direct C(sp³) H oxygenation, which is based on a [1,5] hydrogen shift process of a transient alkoxy radical that is formed by formal hydration of the olefin.     

Iron‐Catalyzed Chemoselective ortho Arylation of Aryl Imines by Directed C?H Bond Activation

No Fe‐ar : Iron catalyzes an imine‐directed C? H bond activation to introduce an ortho‐aryl group to an acetophenone‐derived imine using a diarylzinc reagent (see scheme), whereas palladium catalyzes the conventional substitution reaction . The title reaction features mild and selective C? H bond activation in the presence of aryl bromide, chloride, or sulfonate groups, and 1,2‐dichloroisobutane is essential to achieve such selectivity.

     

Use of LC–HRMS in full scan‐XIC mode for multi‐analyte urine drug testing – a step towards a ‘black‐box’ solution?

The influx of new psychoactive substances (NPS) has created a need for improved methods for drug testing in toxicology laboratories. The aim of this work was to design, validate and apply a multi‐analyte liquid chromatography–high‐resolution mass spectrometry (LC–HRMS) method for screening of 148 target analytes belonging to the NPS class, plant alkaloids and new psychoactive therapeutic drugs. The analytical method used a fivefold dilution of urine with nine deuterated internal standards and injection of 2 μl. The LC system involved a 2.0 μm 100 × 2.0 mm YMC‐UltraHT Hydrosphere‐C₁₈ column and gradient elution with a flow rate of 0.5 ml/min and a total analysis time of 6.0 min. Solvent A consisted of 10 mmol/l ammonium formate and 0.005% formic acid, pH 4.8, and Solvent B was methanol with 10 mmol/l ammonium formate and 0.005% formic acid. The HRMS (Q Exactive, Thermo Scientific) used a heated electrospray interface and was operated in positive mode with 70 000 resolution. The scan range was 100–650 Da, and data for extracted ion chromatograms used ± 10 ppm tolerance. Product ion monitoring was applied for confirmation analysis and for some selected analytes also for screening. Method validation demonstrated limited influence from urine matrix, linear response within the measuring range (typically 0.1–1.0 μg/ml) and acceptable imprecision in quantification (CV <15%). A few analytes were found to be unstable in urine upon storage. The method was successfully applied for routine drug testing of 17 936 unknown samples, of which 2715 (15%) contained 52 of the 148 analytes. It is concluded that the method design based on simple dilution of urine and using LC–HRMS in extracted ion chromatogram mode may offer an analytical system for urine drug testing that fulfils the requirement of a ‘black box’ solution and can replace immunochemical screening applied on autoanalyzers. Copyright © 2017 John Wiley & Sons, Ltd.     

Iron‐Catalyzed Chemoselective ortho Arylation of Aryl Imines by Directed C?H Bond Activation

Naheliegende Alternative : Eine eisenkatalysierte Imin‐gesteuerte C‐H‐Aktivierung mit einem Diarylzinkreagens führt eine Arylgruppe in ortho‐Stellung an einem von Acetophenon abgeleiteten Imin ein (siehe Schema); mit einem Palladiumkatalysator tritt dagegen eine gewöhnliche Substitution auf. Die Titelreaktion ist eine milde C‐H‐Aktivierung, die in Gegenwart von 1,2‐Dichlorisobutan mit Arylbromiden, ‐chloriden oder ‐sulfonaten selektiv verläuft.

     

Hybrid Molecular Systems Containing Tetrathiafulvalene and Iron‐Alkynyl Electrophores: Five‐Component Functional Molecules Obtained from C?H Bond Activation

Treatment of [Cp*(dppe)Fe? C?C‐TTFMe₃] ( 1 ) with Ag[PF₆] (3 equiv) in DMF provides the binuclear complex [Cp*(dppe)Fe?C?C?TTFMe₂?CH? CH?TTFMe₂?C?C=Fe(dppe)Cp*][PF₆]₂ ( 2 [PF₆]₂) isolated as a deep‐blue powder in 69 % yield. EPR monitoring of the reaction and comparison of the experimental and calculated EPR spectra allowed the identification of the radical salt [Cp*(dppe)Fe?C?C?TTFMe₂?CH][PF₆]₂ ([ 1‐CH ][PF₆]) an intermediate of the reaction, which results from the activation of the methyl group attached in vicinal position with respect to the alkynyl–iron on the TTF ligand by the triple oxidation of 1 leading to its deprotonation by the solvent. The dimerization of [ 1‐CH ][PF₆] through carbon–carbon bond formation provides 2 [PF₆]₂. The cyclic voltammetry (CV) experiments show that 2 [PF₆]₂ is subject to two sequential well‐reversible one‐electron reductions yielding the complexes 2 [PF₆] and 2 . The CV also shows that further oxidation of 2 [PF₆]₂ generates 2 [PF₆]_n (n=3–6) at the electrode. Treatment of 2 [PF₆]₂ with KOtBu provides 2 [PF₆] and 2 as stable powders. The salts 2 [PF₆] and 2 [PF₆]₂ were characterized by XRD. The electronic structures of 2 ⁿ⁺ (n=0–2) were computed. The new complexes were also characterized by NMR, IR, Mössbauer, EPR, UV/Vis and NIR spectroscopies. The data show that the three complexes 2 [PF₆]_n are iron(II) derivatives in the ground state. In the solid state, the dication 2 ²⁺ is diamagnetic and has a bis(allenylidene‐iron) structure with one positive charge on each iron building block. In solution, as a result of the thermal motion of the metal–carbon backbone, the triplet excited state becomes thermally accessible and equilibrium takes place between singlet and triplet states. In 2 [PF₆], the charge and the spin are both symmetrically distributed on the carbon bridge and only moderately on the iron and TTFMe₂ electroactive centers.     

Iron‐Mediated Cleavage of C?C Bonds in Vicinal Tricarbonyl Compounds in Water

Three of a kind : Vicinal tricarbonyl compounds undergo C? C cleavage mediated by ferric ions (see scheme). The observed cleavage of ninhydrin and dehydroascorbic acid has relevance for amino acid detection and the metabolism of vitamin C.