Asymmetric epoxidation of unfunctionalized alkenes catalyzed by sugar moiety-modified chiral salen-Mn(III) complexes

Several chiral Schiff-base ligands with sugar moieties at C-3 (3′) or C-5 (5′) of salicylaldehyde were synthesized from reaction of salicylaldehyde derivatives with diamine. These ligands coordinated with Mn(III) to afford the corresponding chiral salen-Mn(III) complexes characterized by FT-IR, MS, and elementary analysis. These complexes were used as catalysts for the asymmetric epoxidation of unfunctionalized alkenes. Only weak enantioselectivity is induced by the chiral sugar moieties at C-3 (3′) or C-5 (5′) in the case of absence of chirality in the diimine bridge moiety. It was also shown that the sugars at C-5 (5′) having the same rotation direction of polarized light as the diimine bridge in the catalyst could enhance the chiral induction in the asymmetric epoxidation, but the sugars with the opposite rotation direction would reduce the chiral induction.     

Enantioselective epoxidation of non-functionalized alkenes using carbohydrate based salen-Mn(III) complexes

Three new salen ligands with carbohydrate moieties were prepared from a salicylaldehyde derivative obtained by reaction of 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose with 3-tert-butyl-5-(chloro-methyl)-2-hydroxybenzaldehyde. These ligands were coordinated with Mn(III) to give three chiral salen-Mn(III) complexes. The complexes were characterized and employed in the asymmetric epoxidation of unfunctionalized alkenes. Catalytic results showed that although there are no chiral groups on the diimine bridge, these complexes had some enantioselectivity, which indicates the carbohydrate moiety has an asymmetric inducing effect in the epoxidation reaction.     

Partially and fully beta-brominated Mn-porphyrins in P450 biomimetic systems: effects of the degree of bromination on electrochemical and catalytic properties

Beta-hexabromo-5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinatomanganese(III) chloride (Mn(III)(Br6TCMPP)Cl) was prepared by selective Br2-hexabromation of its parent non-brominated manganese complex (Mn(III)(TCMPP)Cl), whereas the octabrominated analogue beta-octabromo-5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinatomanganese(III) chloride (Mn(III)(Br8TCMPP)Cl) was synthesized via metallation of the corresponding free-base. Beta-octabromo-5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrin was obtained by demetallation of its brominated Cu(II) derivative, which, in its turn, was prepared by either a Br2 or an N-bromosuccinimide protocol. Relative to Mn(III)(TCMPP)Cl (E(1/2) = -0.16 V vs. normal hydrogen electrode, CH2Cl2), the Mn(III)/Mn(II) reduction potential of Mn(III)(Br8TCMPP)Cl and Mn(III)(Br6TCMPP)Cl showed anodic shifts of 0.43 and 0.33 V, respectively, which corresponded to a linear shift of 0.05 V per bromine added. These manganese complexes were evaluated as cytochrome P450 mimics in catalytic iodosylbenzene (PhIO)-oxidations of cyclohexane and cyclohexene. In aerobic PhIO-oxidation of cyclohexene, epoxidation and allylic autoxidation reactions were inversely related, competitive processes; the most efficient P450-mimics were the least effective autoxidation catalysts. Mn(III)(Br6TCMPP)Cl was more efficient as epoxidation or hydroxylation catalyst than both its fully and non-beta-brominated counterparts were. There was no linear relationship between the catalytic efficiency and both the number of bromine substituents and the Mn(III)/Mn(II) potential; these observations were compared to Lyons system literature data and discussed. Analogously to enzymatic optimum pH effects, an optimum redox potential effect is suggested as relevant in designing and understanding cytochrome P450 biomimetic catalysts.     

Parallel mechanistic studies on the counterion effect of manganese salen and porphyrin complexes on olefin epoxidation by iodosylarenes

Counterions of manganese(III) porphyrin complexes influence diastereoselectivity in cis-stilbene epoxidation and product distribution in cyclohexene epoxidation markedly. In the epoxidation of cis-stilbene by iodosylbenzene carried out in a solvent mixture of CH(3)CN and CH(2)Cl(2), trans-stilbene oxide is the major product in the reaction of manganese complexes bearing a ligating anion (i.e., Cl(-)), whereas cis-stilbene oxide is the dominant product in the reactions of manganese complexes bearing a poorly-ligating anion (i.e., CF(3)SO(4)(-)). In cyclohexene epoxidation, the yields of allylic oxidation products such as cyclohexenol and cyclohexenone are higher when the counterion of the manganese catalysts is Cl(-) than when the counterion is CF(3)SO(4)(-). The product selectivities are also dependent on the nature of iodosylarenes and the axial and porphyrin ligands of the manganese porphyrin catalysts. The observation that product selectivities are different depending on the iodosylarenes may indicate the involvement of multiple oxidants in oxygen atom transfer reactions. These results are compared with those observed in manganese salen-catalyzed epoxidation of olefins by iodosylarenes.     

Polyamino acids as synthetic enzymes: mechanism, applications and relevance to prebiotic catalysis

Polyamino acids, such as polyleucine, behave as synthetic enzymes in the asymmetric epoxidation of chalcone and other electron-deficient alkenes (the Julià-Colonna reaction). The influences of reaction conditions, of the molecular structure of the catalysts and of the scaling-up of the process on the enantioselectivity of the reaction have been determined. The kinetics and mechanism have been investigated using a soluble PEG-polyleucine conjugate, which behaves in a similar way to an enzyme, showing saturation kinetics for both chalcone and HOO-. Enantioselective catalysis is achieved with peptides with as few as five residues and scalemic catalysts show high chiral amplification. Here, we discuss the relevance of these-enzyme like catalysts to prebiotic processes, such as the role of small peptides in the formation of optically active cyanohydrins.     

Oligopeptides as catalysts for asymmetric epoxidation

Oligopeptides are versatile catalysts for the enantioselective epoxidation of electron deficient alkenes, (e.g. alpha,beta-unsaturated ketones) with alkaline hydrogen peroxide. This review describes optimisation of the catalyst, substrate range, synthetic applications of the products and rationalisation of the stereoselectivity by an active site model.     

Salen complexes with bulky substituents as useful tools for biomimetic phenol oxidation research.

The catalytic properties of bulky water-soluble Co-, Cu-, Fe- and Mn-salen complexes in the oxidation of phenolic lignin model compounds have been studied in aqueous water--dioxane solutions (pH 3--10). Mn catalysts were found to oxidize coniferyl alcohol in a same reaction time as horseradish peroxidase (HRP) enzyme and Mn and Co catalysts showed different regioselectivity suggesting a different substrate to catalyst interaction in the oxidative coupling. When the oxidation of material more relevant to plant polyphenolics was studied, the results indicated that the complexes catalyze one- and two-electron oxidations depending on the bulk of the substrate.     

Ligand distortion modes leading to increased chirality content of Katsuki-Jacobsen catalysts

The "chirality content" of Katsuki-Jacobsen epoxidation catalysts are computed with the Avnir continuous chirality measure (CCM). An assessment of Mn(salen) molecules from the Cambridge Structural Database shows there exist some variation in CCM and the chirality content for several triplet state complexes of these catalysts purported in the literature to be the active species show even larger CCM values. Several deformation modes were analyzed to examine how chirality content changes as catalyst distortion is induced. The deformations studied include in-plane deformations, cup-shaped puckering, ligand twisting motions, and step-like deformations. Some distortions lead to increases of chirality while others lead to a decrease in chirality content. The most influential distortion modes that can be used for ligand design are twisting and step induction.     

New dimanganese(III) complexes of pentadentate (N2O3) Schiff base ligands with the [Mn2(mu-OAc)(mu-OR)2]3+ core: synthesis, characterization and mechanistic studies of H2O2 disproportionation

Two new diMn(III) complexes [Mn(2)(III)L(1)(mu-AcO)(mu-MeO)(methanol)(2)]Br (1) and [Mn(2)(III)L(2)(mu-AcO)(mu-MeO)(methanol)(ClO(4))] (2) (L(1)H(3)=1,5-bis(2-hydroxybenzophenylideneamino)pentan-3-ol; L(2)H(3)=1,5-bis(2-hydroxynaphtylideneamino)pentan-3-ol) were synthesized and structurally characterized. Structural studies evidence that these complexes have a bis(mu-alkoxo)(mu-carboxylato) triply bridged diMn(III) core in the solid state and in solution, with two substitution-labile sites--one on each Mn ion--in cis-position. The two complexes show catalytic activity toward disproportionation of H(2)O(2), with saturation kinetics on [H(2)O(2)], in methanol and dimethyl formamide at 25 degrees C. Spectroscopic monitoring of the H(2)O(2) disproportionation reaction suggests that (i) complexes 1 and 2 dismutate H(2)O(2) by a mechanism involving redox cycling between Mn(2)(III) and Mn(2)(IV), (ii) the complexes retain the dinuclearity during catalysis, (iii) the active form of the catalyst contains bound acetate, and (iv) protons favors the formation of inactive Mn(II) species. Comparison to other dimanganese complexes of the same family shows that the rate of catalase reaction is not critically dependent on the redox potential of the catalyst, that substitution of phenolate by naphtolate in the Schiff base ligand favors formation of the catalyst-substrate adduct, and that, in the non-protic solvent, the bulkier substituent at the imine proton position hampers the binding to the substrate.     

PaaSiCats: novel polyamino acid catalysts

The abilities of five polyamino acids (Paa's) to catalyse the asymmetric epoxidation of enones 1-7 under three sets of reaction conditions were compared: polyneo-pentylglycine and polyleucine showed distinct advantages in most circumstances. All five polymers were adsorbed onto silica and from this further study, immobilised polyneo-pentylglycine (PLNSi) and polyleucine (PLLSi) were shown to be the catalysts of choice for the asymmetric epoxidation of less-reactive alpha,beta-unsaturated ketones.     

In situ generated polypyrazolylborate-copper complexes as cyclopropanation catalysts

Polypyrazolylborate-copper complexes with electron withdrawing or donating groups on the pyrazoles were examined as catalysts for the cyclopropanation of alkenes with ethyl diazoacetate. The electron-deficient complexes were much more effective catalysts and afforded rapid consumption of the ethyl diazoacetate and generally favored cyclopropanation over the completing dimerization of the ethyl diazoacetate. Given the ease with which the starting materials can be prepared and the simplicity of in situ catalyst generation, these scorpionates afford a convenient new family of cyclopropanation catalysts.     

Synthesis and Characterization of New Lutidinium Ionic Liquid-Supported Vanadylsalicylaldoxime Complex for Catalytic Application in Epoxidation Reaction

A new chelating task-specific ionic liquid (TSIL), lutidinium-based salicylaldoxime ( LSOH ), and its square pyramidal vanadyl(II) complex (VO(LSO)₂) have been successfully synthesized and structurally characterized using elemental (CHN), spectral, and thermal analyses. The catalytic activity of the lutidinium-salicylaldoxime complex (VO(LSO)₂) in the alkene epoxidation reactions was studied under various reaction conditions, such as solvent effect, alkene/oxidant molar ratio, pH, reaction temperature, reaction time, and the catalyst dose. The results demonstrated that the CHCl₃ solvent, 1 : 3 of the cyclohexene/H₂O₂ ratio, pH 8, temperature of 340 K, and catalyst dose of 0.012 mmol are assigned as the optimum conditions for achieving maximum catalytic activity for VO(LSO)₂. Moreover, the VO(LSO)₂ complex has the potential for application in the effective and selective epoxidation of alkenes. Notably, under optimal VO(LSO)₂ conditions, cyclic alkenes convert more efficiently to their corresponding epoxides than linear alkenes.     

Efficient biomimetic catalytic epoxidation of polyene polymers by manganese porphyrins

Two polyene polymers, cis-polybutadiene and cis-polyisoprene, were transformed into polyepoxides under mild conditions. The epoxidation of these two polyene polymers is stereospecific, giving cis-epoxides as products. All factors controlling the reaction rate, such as the nature of the catalyst, the oxygen donor and the presence of bases as axial ligands, were studied. The optimum results were obtained when iodosylbenzene was used as the oxygen donor, Mn(TpFPP)Cl as the catalyst and imidazole as the axial ligand. Under these optimum conditions the turnover number was found to be 71. These results render this system promising for the epoxidation of polyene polymers in a more general way.     

Evaluating hydrogen bond interactions in enzymes containing Mn(III)-histidine complexation using manganese-imidazole complexes

It is often difficult to control hydrogen bond interactions in small molecule compounds that model metalloenzyme active sites. The imidazole-containing ligands 4,5-dicarboxyimidazole (H(3)DCBI) and 4,5-dicarboxy- N-methylimidazole (H(2)MeDCBI) allow examination of the effects of internal hydrogen bonding between carboxylate and imidazole nitrogen atoms. A new series of mononuclear manganese imidazole complexes have been prepared using these ligands: Mn(III)(salpn)(H(2)DCBI)(DMF) (1), Mn(III)(salpn)(HMeDCBI) (2), Mn(III)(dtsalpn)(HMeDCBI) (3), [Mn(IV)(dtsalpn)(HMeDCBI)]PF(6) (4), Mn(III)(salpn)(H(2)DCBI) (5), Mn(III)(dtsalpn)(H(2)DCBI) (6), and Mn(IV)(dtsalpn)(H(2)DCBI)PF(6) (8). Complexes 1, 2, 3, 5, and 6 have been prepared by direct reaction of salpn [salpn=(salicylideneaminato)-1,3-diaminopropane)] or dtsalpn [dtsalpn=(3,5-di- t-butylsalicylideneaminato)-1,3-diaminopropane)] and H(3)DCBI and H(2)MeDCBI with Mn(III) acetate, while complexes 4 and 8 were made by bulk electrolysis of complex 3 or 6 in dichloromethane. Complexes 1, 2, and 6 were characterized by X-ray diffraction. The impact of hydrogen bonding interactions of the complexes has been demonstrated by X-ray diffraction, cyclic voltammetry, and EPR spectroscopy. In all complexes the central metal ion is present in a six-coordinate geometry. Magnetic susceptibility measurements confirm the spin and oxidation states of the complexes. The cyclic voltammograms of 3 and 6 in dichloromethane reveal single, reversible redox waves with E(1/2)=600 mV and 690 mV, respectively. The X-band EPR spectrum of 4 shows a broad signal around g=4.4, and the corresponding complex 8 possesses a broad signal at slightly lower field ( g=5.5) than 4. These studies demonstrate that even small changes in the effective charge of the imidazole ligand can have a profound impact on the structure, spectroscopy, and magnetism of manganese(IV) complexes. We use these observations to present a model that may explain the origin of the g=4.1 signal in the S(2) state of photosystem II.     

Catalytic oxidation of alkenes by manganese(III) porphyrin-encapsulated Al, V, Si-mesoporous molecular sieves

Cationic manganese-porphyrin, [meso-tetrakis(4-trimethylammoniophenyl)porphyrinato]manganese(III) pentachloride (MnTAPP), has been prepared and encapsulated into mesoporous molecular sieves Al-MCM-41 and V-MCM-41, containing different amounts of Al and V, respectively. The catalytic activities of these heterogeneous materials were tested in the liquid phase oxidation of cyclohexene and styrene in acetonitrile with iodosylbenzene (PhIO) as oxygen source. Both types of catalysts were active in the oxidation reaction. MnTAPP encapsulated in Al-MCM-41 produces allylic oxidation products alone and no epoxide with styrene was found. However, it produces both epoxide and allylic oxidation products with cyclohexene. At the same time, MnTAPP encapsulated in V-MCM-41 produces epoxide as major product and little allylic oxidation product with styrene, while both epoxide and allylic oxidation products were obtained with cyclohexene. It is suggested that the regioselective effect is due to relatively more acidic Al-MCM-41 than V-MCM-41 which could make the CC bond unreactive towards epoxidation and produces allylic oxidation product. With increasing Al or V content in the support, the porphyrin loading was found to increase, which in turn increases the catalytic activity of the heterogeneous systems. The heterogeneous catalysts were reused for three times. The selectivity of these heterogeneous catalysts does not change appreciably even after three times of reusing, but their catalytic activity decreases marginally. This may be attributed to catalyst leaching and/or decomposition of MnTAPP complex under the reaction conditions.     

Molecular basis of chromium insulin interactions

The physiological role of chromium (III) in diabetes mellitus has been an area of inconclusive research for many years. It is of great interest to explore the interactions made by chromium (III) to get a better insight into their role in glucose metabolism. To understand the molecular basis of chromium action we have carried out spectroscopic and crystallographic investigations on the binding of Cr(III)-Salen with insulin, as Cr(III)-Salen is reported to result in the enhancement of insulin activity. The Cr(III)-insulin complex formation has been characterised at two pHs, viz., 3.5 and 9.0 using UV-Vis and fluorescence studies. The crystallographic analysis of Cr(III)-Salen soaked cubic insulin crystals, using anomalous difference Fourier method, revealed B21 Glu to be the binding site for chromium (III).     

SBA immobilized phosphomolybdic acid: Efficient hybrid mesostructured heterogeneous catalysts

SBA-15 and SBA-3 mesoporous silicas are synthesised by P123 and CTAB surfactants via hydrothermal and liquid phase deposition procedures, respectively. An inorganic-organic hybrid mesoporous material is then synthesised by functionalization of SBA-15 with aminopropyl functional groups via grafting method. After characterization, effect of immobilizing support and functional groups on intercalation of phosphomolybdic acid (H₃PMo₁₂O₄₀) is taken into consideration. The immobilization pattern is discussed and supported H₃PMo₁₂O₄₀ catalysts are characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), EDX, inductively coupled plasma (ICP), FT-IR, and UV-vis analysis. The newly synthesised hybrid catalysts are investigated for epoxidation of cyclooctene in presence of hydrogen peroxide as oxidant. The reaction mechanism is discussed. Furthermore, effects of different immobilizing supports and functionalization on catalyst activity, stability, and reusability are taken into consideration. Similar catalytic reactions are carried out with pristine supports and neat H₃PMo₁₂O₄₀ (homogeneous). Results reveal that the mesostructured phosphomolybdic acid based catalysts are shown to be efficient and selective heterogeneous catalysts for oxidation of alkenes.     

Antitumor activity of Mn(III) complexes in combination with phototherapy and antioxidant therapy

Manganese (Mn) is an essential trace element and trivalent Mn complexes have been used as oxidation catalysts and enzyme mimetics. We studied the cytotoxicity of Mn(III) derivatives of citrate, pyrophosphate and salicylene diamine (respectively, MnCit, MnPPi and EUK8) toward HeLa cells stressed by ultraviolet irradiation and the effect of the co-administration of ascorbate and para-amino salicylate (PAS) on cell viability. Metal complexes enhanced the lethality of irradiated cells, and this effect was even more pronounced when ascorbate was co-administered with Mn(III) species. The active role of Mn(III) compounds in the antitumor activity was demonstrated by the treatment of the cells with the chelator PAS, which restored the viability of both non-irradiated and UV-irradiated cells. The association of the Mn(III) metallodrugs with radiation and an antioxidant proved to be a very effective approach to chemotherapy.     

The development of new methods for the recycling of chiral catalysts

This article discusses different methods for the recycling of chiral catalysts, including heterogenization of the soluble catalyst on an insoluble inorganic or organic support, membrane filtration of homogeneously soluble catalysts, precipitation, and two-phase systems. In principle, all the methods presented enable the repeated use of a chiral catalyst without loss of activity and/or enantioselectivity. Examples will be given from laboratory and industrial processes, incuding hydrogenations, ketone reductions, epoxidations, dihydroxylations, diethylzinc additions and Diels-Alder reactions catalyzed by chemocatalysts or biocatalysts. Different approaches for cyanation, hydrogenation and epoxidation are compared. Data from industrial processes include the production of metalochlor, the production of (-)-menthol and the production of L-tert-leucine.     

Optically active β-ketoiminato manganese(III) complexes as efficient catalysts in enantioselective aerobic epoxidation of unfunctionalized olefins

A novel manganese(III) complex having an optically active N, N′-ethylenebis-β-ketoimine ligand was prepared and characterized crystallographically. The manganese(III) complexes behave as effective catalysts in enantioselective epoxidation of unfunctionalized olefins by combined use of molecular oxygen, an oxidant, and pivalaldehyde, a reductant. Dihydronaphthalene derivatives were converted into the corresponding optically active epoxides with good to high enantioselectivities.