Salen Manganese Research Articles

ChemInform Abstract: Manganese‐Catalyzed Late‐Stage Aliphatic C—H Azidation.

We report a manganese-catalyzed aliphatic C–H azidation reaction that can efficiently convert secondary, tertiary, and benzylic C–H bonds to the corresponding azides. The method utilizes aqueous sodium azide solution as the azide source and can be performed under air. Besides its operational simplicity, the potential of this method for late-stage functionalization has been demonstrated by successful azidation of various bioactive molecules with yields up to 74%, including the important drugs pregabalin, memantine, and the antimalarial artemisinin. Azidation of celestolide with a chiral manganese salen catalyst afforded the azide product in 70% ee, representing a Mn-catalyzed enantioselective aliphatic C–H azidation reaction. Considering the versatile roles of organic azides in modern chemistry and the ubiquity of aliphatic C–H bonds in organic molecules, we envision that this Mn-azidation method will find wide application in organic synthesis, drug discovery, and chemical biology.

Reverse Catalase Reaction: Dioxygen Activation via Two-Electron Transfer from Hydroxide to Dioxygen Mediated By a Manganese(III) Salen Complex.

Although atmospheric dioxygen is regarded as the most ideal oxidant, O2 activation for use in oxygenation reactions intrinsically requires a costly sacrificial reductant. The present study investigated the use of aqueous alkaline solution for O2 activation. A manganese(III) salen complex, Mn(III)(salen)(Cl), in toluene reacts with aqueous KOH solution under aerobic conditions, which yields a di-μ-oxo dimanganese(IV) salen complex, [Mn(IV)(salen)]2(μ-O)2. The (18)O isotope experiments show that (18)O2 is indeed activated to give [Mn(IV)(salen)]2(μ-(18)O)2 via a peroxide intermediate. Interestingly, the (18)OH(-) ion in H2(18)O was also incorporated to yield [Mn(IV)(salen)]2(μ-(18)O)2, which implies that a peroxide species is also generated from (18)OH(-). The addition of benzyl alcohol as a stoichiometric reductant selectively inhibits the (18)O incorporation from (18)OH(-), indicating that the reaction of Mn(III)(salen)(Cl) with OH(-) supplies the electrons for O2 reduction. The conversion of both O2 and OH(-) to a peroxide species is exactly the reverse of a catalase-like reaction, which has a great potential as the most efficient O2 activation. Mechanistic investigations revealed that the reaction of Mn(III)(salen)(Cl) with OH(-) generates a transient species with strong reducing ability, which effects the reduction of O2 by means of a manganese(II) intermediate.

Manganese Catalyzed C-H Halogenation.

The remarkable aliphatic C-H hydroxylations catalyzed by the heme-containing enzyme, cytochrome P450, have attracted sustained attention for more than four decades. The effectiveness of P450 enzymes as highly selective biocatalysts for a wide range of oxygenation reactions of complex substrates has driven chemists to develop synthetic metalloporphyrin model compounds that mimic P450 reactivity. Among various known metalloporphyrins, manganese derivatives have received considerable attention since they have been shown to be versatile and powerful mediators for alkane hydroxylation and olefin epoxidation. Mechanistic studies have shown that the key intermediates of the manganese porphyrin-catalyzed oxygenation reactions include oxo- and dioxomanganese(V) species that transfer an oxygen atom to the substrate through a hydrogen abstraction/oxygen recombination pathway known as the oxygen rebound mechanism. Application of manganese porphyrins has been largely restricted to catalysis of oxygenation reactions until recently, however, due to ultrafast oxygen transfer rates. In this Account, we discuss recently developed carbon-halogen bond formation, including fluorination reactions catalyzed by manganese porphyrins and related salen species. We found that biphasic sodium hypochlorite/manganese porphyrin systems can efficiently and selectively convert even unactivated aliphatic C-H bonds to C-Cl bonds. An understanding of this novel reactivity derived from results obtained for the oxidation of the mechanistically diagnostic substrate and radical clock, norcarane. Significantly, the oxygen rebound rate in Mn-mediated hydroxylation is highly correlated with the nature of the trans-axial ligands bound to the manganese center (L-Mn(V)═O). Based on the ability of fluoride ion to decelerate the oxygen rebound step, we envisaged that a relatively long-lived substrate radical could be trapped by a Mn-F fluorine source, effecting carbon-fluorine bond formation. Indeed, this idea led to the discovery of the first Mn-catalyzed direct aliphatic C-H fluorination reactions utilizing simple, nucleophilic fluoride salts. Mechanistic studies and DFT calculations have revealed a trans-difluoromanganese(IV) species as the key fluorine transfer intermediate. In addition to catalyzing normal (19)F-fluorination reactions, manganese salen complexes were found to enable the incorporation of radioactive (18)F fluorine via C-H activation. This advance represented the first direct Csp(3)-H bond (18)F labeling with no-carrier-added [(18)F]fluoride and facilitated the late-stage labeling of drug molecules for PET imaging. Given the high reactivity and enzymatic-like selectively of metalloporphyrins, we envision that this new Heteroatom-Rebound Catalysis (HRC) strategy will find widespread application in the C-H functionalization arena and serve as an effective tool for forming new carbon-heteroatom bonds at otherwise inaccessible sites in target molecules.

Manganese-catalyzed late-stage aliphatic C-H azidation.

We report a manganese-catalyzed aliphatic C-H azidation reaction that can efficiently convert secondary, tertiary, and benzylic C-H bonds to the corresponding azides. The method utilizes aqueous sodium azide solution as the azide source and can be performed under air. Besides its operational simplicity, the potential of this method for late-stage functionalization has been demonstrated by successful azidation of various bioactive molecules with yields up to 74%, including the important drugs pregabalin, memantine, and the antimalarial artemisinin. Azidation of celestolide with a chiral manganese salen catalyst afforded the azide product in 70% ee, representing a Mn-catalyzed enantioselective aliphatic C-H azidation reaction. Considering the versatile roles of organic azides in modern chemistry and the ubiquity of aliphatic C-H bonds in organic molecules, we envision that this Mn-azidation method will find wide application in organic synthesis, drug discovery, and chemical biology.

Electrocatalytic oxidation of methanol on glassy carbon electrode modified with nickel–manganese salen complexes encapsulated in mesoporous zeolite A

Nickel and manganese salen complexes were simultaneously encapsulated in the supercages of the mesoporous zeolite A by using the flexible ligand method. The electrochemical behavior and electrocatalytic activity toward the electrooxidation of methanol on glassy carbon electrode coated with NiMnsalenA (NiMnsalenA/GCE) in 0.1M NaOH solution were studied by cyclic voltammetry (CV), chronoamperometry (CA) and AC electrochemical impedance spectroscopy (EIS). The results showed that the addition of small amounts of Mn species can give rise to much higher electrocatalytic activity than the pure NisalenA toward the oxidation of methanol, mainly due to a synergetic effect that may originate from the interaction of Ni(salen) and Mn(salen) and/or the formation of dinuclear salen complexes via the lattice oxygen of the zeolitic host. Kinetic parameters such as the electron transfer coefficient α, the rate constant ks of the electrode reaction and the charge transfer coefficient of the catalytic reaction, αn were determined to be 0.40, 1.898s−1 and 0.43, respectively, and the detection limit was found to be 97.66μM. The mechanism of electrocatalytic oxidation of methanol on NiMnsalenA/GCE was investigated and proposed to be done by reaction with Ni3+(salen)O(OH) and also direct electro-oxidation reaction. The impedance behaviors showed different patterns at different applied potentials, indicating the changes of the rate-determining step, from the methanol electrooxidation leading to the formation of intermediates on the surface of electrode gradually to the oxidation and removal of adsorbed intermediates. The influence of methanol concentration on the impedance behaviors was also studied and the results demonstrated that the semidiameters of the Nyquist diagrams decreased with the increase of methanol concentration, signifying the acceleration of the reaction rate of methanol electrooxidation.

SINTESIS 7-FORMILINDOL SEBAGAI BAHAN DASAR PEMBENTUK KATALIS EPOKSIDASI BARU (SYNTHESIS OF 7-FORMYLINDOLE AS PRECURSOR OF NEW EPOXIDATION CATALYSTS)

Manganese (III) salen complexes have been reported as epoxidation catalysts. It is caused a major breakthrough in the enantioselective epoxidation of alkenes into epoxide compounds. This catalyst was synthesized from salicylaldehyde derivatives. Based on the structure, salicylaldehyde is an isosteric nature of 7-folmylindole, consequently opened the door to an array of fascinating and versatile ligand systems, and offer tremendous scope for molecular designe, because of the greatly enhanced capacity for substitution of indoles compared with phenols. Initial target of the project to synthesize of 7-formylindole. There are numerous strategies and methodes to achieve the target molecules. Further study of reaction mechanism of a useful target compound could be explanated and developed as a new class of catalyst. Key word: Epoxidation catalyst, indole, organometal catalyst.

Peroxide detected in imidazolium-based ionic liquids and approaches for reducing its presence in aqueous and non-aqueous environments

Peroxide species appearing in imidazolium-based ionic liquids could be removed by salen–manganese complexes or the enzyme catalase.

Manganese (III) Salen Supported Onto Hydrous Zirconia: Synthesis, Characterization, and Solvent Free Aerobic Oxidation of Styrene

Solid catalysts comprising manganese salen and hydrous zirconia were synthesized and characterized, and catalytic activity was evaluated by carrying out solvent-free liquid phase aerobic oxidation of styrene. As solid catalysts show high conversion of styrene with good selectivity toward benzaldehyde and styrene epoxide. The recovery of the catalyst was readily accomplished by simple filtration. The recycled catalyst can be used up to four cycles without any loss in conversion as well as selectivity.

A comparative study of the asymmetric epoxidation of aromatic olefins using the first generation manganese salen epoxidation catalysts and their light fluorous variants: an interesting discovery on the use of benzotrifluoride as a cosolvent

The asymmetric epoxidation of aromatic olefins using optically active first generation manganese salen catalysts and light fluorous variants was examined. Although a slight decrease in the enantioselectivity of the product was observed when light fluorous catalysts were employed, the activities of these catalysts were higher than those of the non-fluorous catalysts. Additionally the influence on enantioselectivity of the oxidation was examined when fluorous cosolvents were used. The enantioselectivity of the oxidation increased with the addition of benzotrifluoride (BTF) regardless of whether a fluorous or non-fluorous salen catalyst was used.

Manganese(III) Salen Complex Immobilized on Fe3O4 Magnetic Nanoparticles: The Efficient, Green and Reusable Nanocatalyst

AbstractA new Fe3O4 magnetic nanoparticles supported manganese salen complex was successfully prepared by attaching manganese acetates to a novel N,N′‐bis(salicylidine)ethylenediamine ligand functionalized Fe3O4. The as‐prepared catalyst was characterized by TGA, XRD, FTIR, VSM, and TEM. It was found to be an efficient catalyst for the synthesis of benzopyranopyrimidines in aqueous medium. High catalytic activity and ease of recovery from the reaction mixture using external magnet, and several reuse times without significant losses in performance are additional eco‐friendly attributes of this catalytic system.

Asymmetric Epoxidation of Olefins with Homogeneous Chiral (Salen) Manganese (III) Complex

Optically active epoxides are known as versatile chiral building blocks in organic synthesis, and many efforts have been directed toward developing asymmetric epoxidation (AE) reaction of olefins. The first major breakthrough in AE using synthetic catalysts was realized by Katsuki and Sharpless in 1980, they achieved enantiomeric excesses (ee’s) greater than 90% in the titanium tartrate-based epoxidation of a variety of allylic alcohols. However, the substrates must bear specific functional groups to achieve the precoordination required for high enantioselectivity. In 1990 Jacobsen et al. and Katsuki et al. announced their independently developed systems for the catalytic AE of unfunctionalized olefins using chiral manganese (III) salen complexes. Since that time, the area of chiral manganese (III)- catalyzed AE has expanded greatly. In this review we will focus on the ligand development and the application of homogeneous chiral (salen) manganese (III)-promoted AE of olefins in recent years. Keywords: Asymmetric epoxidation, Chiral, Manganese, Salen, homogeneous, Ligand, Olefin.

Oxidative aliphatic C-H fluorination with manganese catalysts and fluoride ion

Fluorination is a reaction that is useful in improving the chemical stability and changing the binding affinity of biologically active compounds. The protocol described here can be used to replace aliphatic, C(sp(3))-H hydrogen in small molecules with fluorine. Notably, isolated methylene groups and unactivated benzylic sites are accessible. The method uses readily available manganese porphyrin and manganese salen catalysts and various fluoride ion reagents, including silver fluoride (AgF), tetrabutylammonium fluoride and triethylamine trihydrofluoride (TREAT·HF), as the source of fluorine. Typically, the reactions afford 50-70% yield of mono-fluorinated products in one step. Two representative examples, the fragrance component celestolide and the nonsteroidal anti-inflammatory drug ibuprofen, are described; they produced useful isolated quantities (250-300 mg, ~50% yield) of fluorinated material over periods of 1-8 h. The procedures are performed in a typical fume hood using ordinary laboratory glassware. No special precautions to rigorously exclude water are required.

Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice

The 1918 influenza pandemic caused over 40 million deaths worldwide, with 675,000 deaths in the United States alone. Studies in several experimental animal models showed that 1918 influenza virus infection resulted in severe lung pathology associated with dysregulated immune and cell death responses. To determine if reactive oxygen species produced by host inflammatory responses play a central role in promoting severity of lung pathology, we treated 1918 influenza virus-infected mice with the catalytic catalase/superoxide dismutase mimetic, salen–manganese complex EUK-207 beginning 3 days postinfection. Postexposure treatment of mice infected with a lethal dose of the 1918 influenza virus with EUK-207 resulted in significantly increased survival and reduced lung pathology without a reduction in viral titers. In vitro studies also showed that EUK-207 treatment did not affect 1918 influenza viral replication. Immunohistochemical analysis showed a reduction in the detection of the apoptosis marker cleaved caspase-3 and the oxidative stress marker 8-oxo-2′-deoxyguanosine in lungs of EUK-207-treated animals compared to vehicle controls. High-throughput sequencing and RNA expression microarray analysis revealed that treatment resulted in decreased expression of inflammatory response genes and increased lung metabolic and repair responses. These results directly demonstrate that 1918 influenza virus infection leads to an immunopathogenic immune response with excessive inflammatory and cell death responses that can be limited by treatment with the catalytic antioxidant EUK-207.

Epoxidation of alkenes catalyzed by highly ordered mesoporous manganese–salen-based hybrid catalysts

A series of manganese–salen-based hybrid catalysts, Mn(salen)/C3N2–Schiff–SBA-15 and Mn(salen)/C4N2–Schiff–SBA-15, were demonstrated for the first time by a multistep grafting method. As-prepared hybrid catalysts exhibited well-defined mesostructure including highly ordered 2D hexagonal p6mm pore geometry, large BET surface area (268–293m2g−1), uniform pore size (5.2–6.4nm) as well as high pore volume (0.35–0.41cm3g−1); meanwhile, the structure of the starting manganese–salen complexes and other functionalities (Schiff ligand and C3N2 or C4N2 unit) remained intact in the hybrid catalysts. These hybrid catalysts were subsequently utilized as efficient, selective and reusable catalysts in epoxidation of alkenes including styrene, cyclohexene and 1-phenylcyclohexene by using NaOCl as the oxidant, and the contribution of imidazole or piperazine and Schiff base to the overall catalytic activity of the hybrid catalysts were evaluated and explained.

An Efficient Catalyst Based on Manganese Salen for Hydrosilylation of Carbonyl Compounds

A manganese salen complex is shown to be an effective (pre)catalyst in the hydrosilylation of aldehydes and ketones. The present system features an earth-abundant and inexpensive base metal, low catalyst loading, and functional group tolerance. Mechanistic studies suggest that the reaction likely proceeds through a reduced manganese(III) hydride species that undergoes electrophilic attack by the carbonyl substrates.

Oxygen-Atom Transfer from Iodosylarene Adducts of a Manganese(IV) Salen Complex: Effect of Arenes and Anions on I(III) of the Coordinated Iodosylarene

This paper reports preparation, characterization, and reactivity of iodosylarene adducts of a manganese(IV) salen complex. In order to systematically investigate steric and electronic factors that control reactivity and selectivity, we prepared iodosylarene adducts from iodosylbenzene, iodosylmesitylene, 2,4,6-triethyliodosylbenzene, and pentafluoroiodosylbenzene. We also investigated the effect of anions on I(III) by using chloride, benzoate, and p-toluenesulfonate. Spectroscopic studies using (1)H NMR, electron paramagnetic resonance, infrared spectroscopy, and electrospray ionization mass spectrometry show that these iodosylarene adducts are manganese(IV) complexes bearing two iodosylarenes as external axial ligands. Reactions with thioanisole under the pseudo-first-order conditions show that the electron-withdrawing pentafluorophenyl group and the p-toluenesulfonate anion on I(III) significantly accelerate the oxygen-atom transfer. The high reactivity is correlated with a weakened I-OMn bond, as indicated by IR spectroscopy and mass spectrometry. Stoichiometric reactions with styrenes show that both enantioselectivity and diastereoselectivity are dependent on the arenes and anions on I(III) of the coordinate iodosylarenes. Notably, the pentafluorophenyl group and the p-toluenesulfonate anion suppress the cis-to-trans isomerization in the epoxidation of cis-β-methylstyrene. The present results show that iodosylarene adducts of manganese(IV) salen complexes are indeed active oxygen-atom-transfer reagents and that their reactivity and selectivity are regulated by steric and electronic properties of the arenes and anions on I(III) of the coordinated iodosylarenes.

Effect of substrate and catalyst chirality on the diastereoselective epoxidation of R-(+)-limonene with manganese(III) salen complexes

The asymmetric epoxidation of R-(+)-limonene in the presence of the Jacobsen´s catalyst in its chiral and achiral either homogeneous or heterogeneous (immobilized on Al-MCM-41) forms was studied using in situ generated dimethyldioxirane as oxidizing agent. It was found that the catalytic activity of the chiral and achiral forms of the Jacobsen´s catalyst was very similar either homogeneous or heterogeneous. This result suggests that the preferential formation of cis-(+)-1,2-limonene oxide depends not only on the catalyst chiral center, but also on the substrate chiral center. This represents a clear advantage from the economical point of view since the achiral catalyst is much less expensive than its chiral counterpart.

Oxidation of cycloalkanes with molecular oxygen in the presence of salen metallocomplexes in thermomorphic conditions

The oxidation of cycloalkanes with molecular oxygen, catalyzed by two groups of metallosalen complexes, was studied. The first group consisted of salen complexes with different metals such as Mn, Fe, Co, Ni, Cu, Zn, while the second group was composed of manganese salen complexes with different substituents ( t -butyl electron-donating substituents and/or electron-withdrawing perfluoroalkyl substituents). Mn, Fe and Co salen complexes are the most active catalysts, while Ni, Cu and Zn salen complexes are far less efficient. The introduction of t -butyl electron-donating substituents into Mnsalen complex increases the catalytic activity and catalysts solubility in the reaction mixture. The introduction of perfluoroalkyl electron-withdrawing substituents enhances the catalytic activity and renders the solubility of the catalyst temperature dependent (thermomorphic behaviour), thus allowing one to recover them easily after the reaction by simply cooling the system to room temperature. The synthesis of two new manganese salen complexes with perfluoroalkyl substituents was elaborated. • New strategy for recovering homogeneous catalysts–thermomorphic effect • Fluorous catalysis without fluorous solvent • Synthesis and characterization of two new perfluoroalkyl manganese complexes • Influence of substituents on physico-chemical properties of salen complexes • Influence of substituents in salen complexes on their catalytic activity

Manganese‐Catalyzed Oxidative Benzylic C–H Fluorination by Fluoride Ions

An efficient protocol for the selective fluorination of benzylic C-H bonds is described. The process is catalyzed by manganese salen complexes and uses nucleophilic fluorine sources, such as triethylamine trihydrofluoride and KF. Reaction rates are sufficiently high (30 min) to allow adoption for the incorporation of (18)F fluoride sources for PET imaging applications.

Manganese Salen Complexes with Acid–Base Catalytic Auxiliary: Functional Mimetics of Catalase

Antioxidant therapies have been considered for a wide variety of disorders associated with oxidative stress, and synthetic catalytic scavengers of reactive oxygen species would be clinically superior to stoichiometric ones. Among them, salen-manganese complexes (Mn(Salen)) seem promising, because they exhibit dual functions, i.e. superoxide dismutase- and catalase-mimetic activities. We have been developing enzyme-mimetic Mn(Salen) complexes bearing a functional group that enhances their catalytic activity. Here, we describe the design and synthesis of novel Mn(Salen) complexes with general acid-base catalytic functionality, inspired by the reaction mechanism of catalase. As expected, these Mn(Salen) complexes showed superior catalase-like activity and selectivity, while retaining moderate SOD-like activity. An unsubstituted pyridyl group worked well as a functionality to promote catalase-like activity. The introduced functionality did not alter the redox potential suggesting that the auxiliary-modified complex acted as an acid-base catalyst analogous to catalase. We believe that our approach provides a new design principle for sophisticated catalyst design. Further, the compounds described here appear to be good candidates for use in antioxidant therapy.