Mechanism Of Epoxidation Research Articles

Quantitative Deuterium Isotopic Profiling at Natural Abundance Indicates Mechanistic Differences for Δ12-Epoxidase and Δ12-Desaturase in Vernonia galamensis

Quantitative (2)H NMR spectroscopy can determine the natural abundance ((2)H/(1)H) ratio at each site of a molecule. In natural products, variation in these values is related to the reaction mechanisms in the pertinent biosynthetic pathway. For the first time, this novel approach has been exploited to probe for mechanistic differences in the introduction of different functionalities into a long-chain fatty acid. Vernolic acid, a major component of the seed oil of Vernonia galamensis, contains both an epoxide and a desaturation. The site-specific isotopic distribution ((2)H/(1)H)(i) has been determined for both vernolic acid and linoleic acid isolated from the same V. galamensis oil. It is found that the ((2)H/(1)H) ratio of vernolic acid shows a pattern along the entire length of the chain, consistent with linoleic acid being its immediate precursor. Notably, the C13 relates to the C13 of linoleic acid but not to the C13 of oleic acid. Furthermore, the C12 and C13 positions in vernolic acid are less depleted, consistent with a change in hybridization state from sp(2) to sp(3). However, the C11 position shows a marked relative enrichment in the vernolic acid, implying that it plays a role in the epoxidase but not the desaturase mechanism. Thus, although it can be concluded that the catalytic mechanisms for the epoxidase and desaturase activities are similar, marked differences in the residual ((2)H/(1)H) patterns indicate that the reaction mechanisms are not identical.

Multistate Reactivity in Styrene Epoxidation by Compound I of Cytochrome P450: Mechanisms of Products and Side Products Formation

Density functional theoretical calculations are used to elucidate the epoxidation mechanism of styrene with a cytochrome P450 model Compound I, and the formation of side products. The reaction features multistate reactivity (MSR) with different spin states (doublet and quartet) and different electromeric situations having carbon radicals and cations, as well as iron(III) and iron(IV) oxidation states. The mechanisms involve state-specific product formation, as follows: a) The low-spin pathways lead to epoxide formation in effectively concerted mechanisms. b) The high-spin pathways have finite barriers for ring-closure and may have a sufficiently long lifetime to undergo rearrangement and lead to side products. c) The high-spin radical intermediate, (4)2(rad)-IV, has a ring closure barrier as small as the C--C rotation barrier. This intermediate will therefore lose stereochemistry and lead to a mixture of cis and trans epoxides. The barriers for the production of aldehyde and suicidal complexes are too high for this intermediate. d) The high-spin radical intermediate, (4)2(rad)-III, has a substantial ring closure barrier and may survive long enough time to lead to suicidal, phenacetaldehyde and 2-hydroxostyrene side products. e) The phenacetaldehyde and 2-hydroxostyrene products both originate from crossover from the (4)2(rad)-III radical intermediate to the cationic state, (4)2(cat,z(2) ). The process involves an N-protonated porphyrin intermediate that re-shuttles the proton back to the substrate to form either phenacetaldehyde or 2-hydroxostyrene products. This resembles the internally mediated NIH-shift observed during benzene hydroxylation.

Epoxidation of α,β-unsaturated acids catalyzed by tungstate (VI) or molybdate (VI) in aqueous solvents: a specific direct oxygen transfer mechanism

The epoxidation mechanism of α,β-unsaturated acids catalyzed by Na 2WO 4 or Na 2MoO 4 in aqueous solvents has been studied by means of kinetic experiments, MS, 31P NMR and 13C NMR. The results show Na 2WO 4 or Na 2MoO 4 and H 2O 2 can rapidly form the diperoxocomplex irreversibly in aqueous solvent. 31P NMR and kinetics study reveal that –P O in cis-1-propenylphosphonic acid (CPPA) can fast coordinate to the metal center (Mo or W) of the diperoxocomplex irreversibly to form a stable complex. The subsequent direct oxygen transfer from peroxo bond to double bond is a monomolecular process, thus the epoxidation is zero-order on CPPA. However, 13C NMR shows the –C O in α,β-unsaturated carboxylic acids cannot coordinate to metal center of the diperoxocomplex. Therefore, the oxygen transfer is a bimolecular process and the epoxidation is a first-order reaction on the acids. In the mechanism, the nucleophilic attack of double bond towards the peroxo bond is regarded as through a spiro-transition structure.

Asymmetric epoxidation of cis-1-propenylphosphonic acid (CPPA) catalyzed by chiral tungsten(VI) and molybdenum(VI) complexes

In the presence of 5.0 mol% chiral tungsten(VI) and molybdenum(VI) complexes, the catalytic asymmetric epoxidation of cis-1-propenylphosphonic acid (CPPA) with 30% aqueous H 2O 2 affording (1 R,2 S)-(−)-(1, 2)-epoxypropyl phosphonic acid (fosfomycin) was first described. The enantioselectivities of the tungsten and molybdenum catalysts depend strongly on the ligands, reaction temperature and solvent. In CH 2Cl 2 at 0 °C for 72 h, complex MoO 2[(+)-campy] 2 catalyzed the asymmetric epoxidation in a 100% conversion of CPPA with the highest 80% ee. The mechanism of the present epoxidation could be described as direct oxygen transfer occurred on the interface of the biphasic H 2O–nonprotic system.

New Paradigms for the Peroxy Acid Epoxidation of CC Double Bonds: The Role of the Peroxy Acid s-Trans Conformer and of the 1,2-H Transfer in the Epoxidation of Cyclic Allylic Alcohols

RB3LYP calculations, on reaction of performic acid with cyclic allylic alcohols, demonstrate that the less stable s-trans conformer of peroxy acids can be involved in epoxidations of C=C bonds. Transition structures (TSs) arising from s-trans performic acid retain some of the well-established characteristics of the TSs of the s-cis isomer such as the perpendicular orientation of the O-H peroxy acid bond relative to the C=C bond and a one-step oxirane ring formation. These TSs are very asynchronous but collapse directly (without formation of any intermediate) to the final epoxide-peroxy acid complex via a 1,2-H shift. Thus, our findings challenge the traditional mechanism of peroxy acid epoxidation of C=C bonds by demonstrating that the involvement of the s-trans isomer opens an alternative one-step reaction channel characterized by a 1,2-H transfer. This novel reaction pathway can even overcome, in the case of the reaction of cyclic allylic alcohols in moderately polar solvents (e.g., in dichloromethane), the classical Bartlett's mechanism that is based on the s-cis peroxy acid form and that features a 1,4-H shift. However, the latter mechanism remains strongly favored for the epoxidation of normal alkenes.

Epoxidation of cyclohexene catalyzed by transition-metal substituted $alpha;-titanium arsenate using tert-butyl hydroperoxide as an oxidant

Epoxidation of cyclohexene, using transition-metal substituted α-titanium arsenate {α-TiMAs, where MCu(II), Co(II), Mn(II), Fe(III), Cr(III) and Ru(III)} as a catalyst and dry tert-butyl hydroperoxide as an oxidant, was studied. In the epoxidation reaction, cyclohexene was oxidized to cyclohexene oxide, cyclohexenol and cyclohexenone. It was found that the reactivity of the epoxidation reaction decreased in the order α-TiRuAs>α-TiMnAs>α-TiFeAs>α-TiCrAs>α-TiCoAs>α-TiCuAs. A maximum selectivity for epoxidation of cyclohexene (89.89%) was observed for α-TiRuAs/dryTBHP system after 4 h of reaction when concentrations of the catalyst and the substrate were 0.20 and 20 mmol, respectively. The competitive epoxidation of cyclic olefins were studied and the reactivity-order in the relative rates of epoxidation of cyclic olefins was found to decrease in the order norbornene>cyclooctene>cyclohexene>cyclopentene. The mechanism for epoxidation of cyclohexene catalyzed by α-TiMAs/dryTBHP system is proposed.

Interaction of Water, Alkyl Hydroperoxide, and Allylic Alcohol with a Single-Site Homogeneous Ti−Si Epoxidation Catalyst: A Spectroscopic and Computational Study

Tetrakis(trimethylsiloxy)titanium (TTMST, Ti(OSiMe3)4) possesses an isolated Ti center and is a highly active homogeneous catalyst in epoxidation of various olefins. The structure of TTMST resembles that of the active sites in some heterogeneous Ti-Si epoxidation catalysts, especially silylated titania-silica mixed oxides. Water cleaves the Ti-O-Si bond and deactivates the catalyst. An alkyl hydroperoxide, TBHP (tert-butyl hydroperoxide), does not cleave the Ti-O-Si bond, but interacts via weak hydrogen-bonding as supported by NMR, DOSY, IR, and computational studies. ATR-IR spectroscopy combined with computational investigations shows that more than one, that is, up to four, TBHP can undergo hydrogen-bonding with TTMST, leading to the activation of the O-O bond of TBHP. The greater the number of TBHP molecules that form hydrogen bonds to TTMST, the more electrophilic the O-O bond becomes, and the more active the complex is for epoxidation. An allylic alcohol, 2-cyclohexen-1-ol, does not interact strongly with TTMST, but the interaction is prominent when it interacts with the TTMST-TBHP complex. On the basis of the experimental and theoretical findings, a hydrogen-bond-assisted epoxidation mechanism of TTMST is suggested.

Olefin epoxidation with inorganic peroxides. Solutions to four long-standing controversies on the mechanism of oxygen transfer.

Four controversies on the mechanism of the olefin epoxidation with Mimoun-type complexes, [MoO(O2)2(OPR3)], Herrmann-type complexes, [ReO(O2)2Me], and related inorganic peroxides have inspired industrial and academic researchers in the last three decades. First, is the oxygen transfer from the peroxo complex to the olefin concerted or stepwise? Second, does the oxidant act as an electrophile or a nucleophile? Third, is the mechanism of the stoichiometric reaction also valid for catalytic protocols? Fourth, how can stereochemical information be transferred between oxidant and substrate? In this Account, we discuss answers to the long-standing questions, focusing on recent contributions from quantum chemical calculations.

Epoxidation of cyclohexene catalyzed by transition-metal substituted α-titanium arsenate using tert-butyl hydroperoxide as an oxidant

Epoxidation of cyclohexene, using transition-metal substituted α-titanium arsenate {α-TiMAs, where MCu(II), Co(II), Mn(II), Fe(III), Cr(III) and Ru(III)} as a catalyst and dry tert-butyl hydroperoxide as an oxidant, was studied. In the epoxidation reaction, cyclohexene was oxidized to cyclohexene oxide, cyclohexenol and cyclohexenone. It was found that the reactivity of the epoxidation reaction decreased in the order α-TiRuAs>α-TiMnAs>α-TiFeAs>α-TiCrAs>α-TiCoAs>α-TiCuAs. A maximum selectivity for epoxidation of cyclohexene (89.89%) was observed for α-TiRuAs/dryTBHP system after 4 h of reaction when concentrations of the catalyst and the substrate were 0.20 and 20 mmol, respectively. The competitive epoxidation of cyclic olefins were studied and the reactivity-order in the relative rates of epoxidation of cyclic olefins was found to decrease in the order norbornene>cyclooctene>cyclohexene>cyclopentene. The mechanism for epoxidation of cyclohexene catalyzed by α-TiMAs/dryTBHP system is proposed.

Formation of hydrogen peroxide from H 2 and O 2 over a neutral gold trimer: a DFT study

Our density-functional theory study of the formation of hydrogen peroxide over a neutral Au 3 cluster details a reaction path with activation barriers less than 10 kcal/mol. The reactions proceed on the edges and one side of the triangular Au 3 cluster which makes this mechanism viable for a cluster in contact with a support surface. The Au 3 cluster remains in a triangular geometry throughout the reaction but the electron population on the Au trimer during the catalytic cycle proper, as calculated with the Natural Bond Orbital method, varies from a charge of +0.304 (cationic) (Au 3O 2H 2) to −0.138 (anionic) (Au 3H 2). Au 3 in the reaction initiation intermediate, Au 3O 2, is also cationic in character with a charge of +0.390. It is interesting to note that the interaction of Au 3 with a model oxidic support, TS-1, was essentially neutral in character, the Au 3 charge population being −0.044. Formation of hydrogen peroxide does not involve breaking the OO bond, but does break the HH bond in a step that is rate limiting under standard conditions. The highest energy barrier in the cycle is 8.6 kcal/mol for desorption of H 2O 2 from Au 3H 2. Adsorption of H 2O 2 on this site is unactivated. This route to formation of hydrogen peroxide combined with existing mechanisms for epoxidation by H 2O 2 over TS-1 gives a fully plausible, energetically favorable, closed cycle for epoxidation of propylene by H 2 and O 2 over Au/TS-1 catalysts. Thus, isolated molecular gold clusters can act as viable sites for this reaction.

Epoxidation of cyclic allylic alcohols on titania–silica aerogels studied by attenuated total reflection infrared and modulation spectroscopy

Epoxidation of cyclohex-2-en-1-ol and cyclooct-2-en-1-ol on titania–silica aerogel catalysts using t-butylhydroperoxide (TBHP) as oxidant was studied by in situ attenuated total reflection (ATR) Fourier transform infrared spectroscopy. Probing of the catalytic liquid–solid interface revealed different adsorption behaviors for the two allylic alcohols on the aerogel. Cyclohexenol was found to adsorb stronger and less reversible on the catalyst surface and Ti sites than cyclooctenol. The spectroscopic measurements under working conditions support the previously proposed hydroxy-assisted mechanism for the formation of cyclohexenol oxide and the silanol-assisted mechanism for cyclooctenol epoxidation. The evidence of the former is traced to the occurrence of a framework vibration upon adsorption of cyclohexenol, whereas the latter is supported by large negative bands of the silanol groups at 3700 and 980 cm −1 in the case of cyclooctenol epoxidation.

EFFICIENT NEW SYNTHESES OF POLYCYCLIC AROMATIC HYDROCARBON ORTHO-QUINONES AND THEIR 2′-DEOXYRIBONUCLEOSIDE ADDUCTS

Three mechanisms have been proposed to explain the carcinogenic activities of polycyclic aromatic hydrocarbons (PAHs). On the basis of the nature of the active metabolites involved, they may be termed: the diol epoxide mechanism, the quinone mechanism, and the radical-cation mechanism. In connection with studies to evaluate the relative importance of these pathways, we required practical methods for the syntheses of the active PAH metabolites involved. We now report efficient new synthesis of the o-quinones of benzo[a]pyrene (BPQ), 7,12-dimethylbenz[a]anthracene (DMBAQ), and benz[a]anthracene (BAQ). These quinones are convenient synthetic precursors of the related o-catechols, trans-dihydrodiols, and diol epoxides, as well as the stable adducts of the o-quinones with 2-deoxyadenosine and 2′-deoxyguanosine.

(Salen)Mn-catalyzed epoxidation of alkenes: a two-zone process with different spin-state channels as suggested by DFT study.

[structure: see text] A novel (two-zone process with different spin-state channels) mechanistic picture for the Jacobsen-Katsuki reaction is presented that provides insight into the still elusive understanding of the epoxidation mechanism. For the first time, we show that the salen moiety of the catalyst can be explicitly involved in the epoxidation process.

Enantioselective Total Syntheses of (+)‐Decursin and Related Natural Compounds Using Catalytic Asymmetric Epoxidation of an Enone.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The remarkable reactivity of high oxidation state ruthenium and osmium polypyridyl complexes.

There is a remarkable redox chemistry of higher oxidation state M(IV)-M(VI) polypyridyl complexes of Ru and Os. They are accessible by proton loss and formation of oxo or nitrido ligands, examples being cis-[RuIV(bpy)2(py)(O)]2+ (RuIV=O2+, bpy=2,2'-bipyridine, and py=pyridine) and trans-[OsVI(tpy)(Cl)2(N)]+ (tpy=2,2':6',2' '-terpyridine). Metal-oxo or metal-nitrido multiple bonding stabilizes the higher oxidation states and greatly influences reactivity. O-atom transfer, hydride transfer, epoxidation, C-H insertion, and proton-coupled electron-transfer mechanisms have been identified in the oxidation of organics by RuIV=O2+. The Ru-O multiple bond inhibits electron transfer and promotes complex mechanisms. Both O atoms can be used for O-atom transfer by trans-[RuVI(tpy)(O)2(S)]2+ (S=CH3CN or H2O). Four-electron, four-proton oxidation of cis,cis-[(bpy)2(H2O)RuIII-O-RuIII(H2O)(bpy)2]4+ occurs to give cis,cis-[(bpy)2(O)RuV-O-RuV(O)(bpy)2]4+ which rapidly evolves O2. Oxidation of NH3 in trans-[OsII(tpy)(Cl)2(NH3)] gives trans-[OsVI(tpy)(Cl)2(N)]+ through a series of one-electron intermediates. It and related nitrido complexes undergo formal N- transfer analogous to O-atom transfer by RuIV=O2+. With secondary amines, the products are the hydrazido complexes, cis- and trans-[OsV(L3)(Cl)2(NNR2)]+ (L3=tpy or tpm and NR2-=morpholide, piperidide, or diethylamide). Reactions with aryl thiols and secondary phosphines give the analogous adducts cis- and trans-[OsIV(tpy)(Cl)2(NS(H)(C6H4Me))]+ and fac-[OsIV(Tp)(Cl)2(NP(H)(Et2))]. In dry CH3CN, all have an extensive multiple oxidation state chemistry based on couples from Os(VI/V) to Os(III/II). In acidic solution, the OsIV adducts are protonated, e.g., trans-[OsIV(tpy)(Cl)2(N(H)N(CH2)4O)]+, and undergo proton-coupled electron transfer to quinone to give OsV, e.g., trans-[OsV(tpy)(Cl)2(NN(CH2)4O)]+ and hydroquinone. These reactions occur with giant H/D kinetic isotope effects of up to 421 based on O-H, N-H, S-H, or P-H bonds. Reaction with azide ion has provided the first example of the terminal N4(2-) ligand in mer-[OsIV(bpy)(Cl)3(NalphaNbetaNgammaNdelta)]-. With CN-, the adduct mer-[OsIV(bpy)(Cl)3(NCN)]- has an extensive, reversible redox chemistry and undergoes NCN(2-) transfer to PPh3 and olefins. Coordination to Os also promotes ligand-based reactivity. The sulfoximido complex trans-[OsIV(tpy)(Cl)2(NS(O)-p-C6H4Me)] undergoes loss of O2 with added acid and O-atom transfer to trans-stilbene and PPh3. There is a reversible two-electron/two-proton, ligand-based acetonitrilo/imino couple in cis-[OsIV(tpy)(NCCH3)(Cl)(p-NSC6H4Me)]+. It undergoes reversible reactions with aldehydes and ketones to give the corresponding alcohols.

Density functional theory study of the ethylene epoxidation over Ti-substituted silicalite (TS-1)

The mechanism of ethylene epoxidation with hydrogen peroxide over Ti-substituted silicalite (TS-1) catalyst was investigated by using both the cluster and embedded cluster approaches at the B3LYP/6-31G(d) level of theory. The complete catalytic cycle was determined. The epoxidation of ethylene consists of three steps. First, the chemisorption of H2O2 at the Ti active site forms the oxygen donating TiOOH species and then the transfer of an oxygen atom from the TiOOH species to the adsorbed ethylene. The final step is the dehydration of the TiOH species to regenerate to active center. The oxygen atom transfer step was found to be the rate-limiting step with the zero-point energy corrected barrier of 17.0 kcal/mol using the embedded cluster model at B3LYP/6-31G(d) level of theory, which is in agreement with the experimental estimate of about 16.7 kcal/mol. Regeneration of the active center by dehydration of the TiOOH species was found to have a rather small barrier and the overall process is exothermic. Our results also show that inclusion of the effects of the zeolite crystal framework is crucial for obtaining quantitative energetic information. For instance, the Madelung potential increases the barrier of the oxygen atom transfer step by 5.0 kcal/mol.

Mechanism of Olefin Epoxidation by Transition Metal Peroxo Compounds

AbstractFor Abstract see ChemInform Abstract in Full Text.

Mechanistic study of an improbable reaction: alkene dehydrogenation by the delta12 acetylenase of Crepis alpina.

The mechanism by which the fatty acid acetylenase of Crepis alpina catalyzes crepenynic acid ((9Z)-octadeca-9-en-12-ynoic acid) production from linoleic acid has been probed through the use of kinetic isotope effect (KIE) measurements. This was accomplished by incubating appropriate mixtures of regiospecifically deuterated isotopomers with a strain of Saccharomyces cerevisiae expressing a functional acetylenase. LC/MS analysis of crepenynic acid obtained in these experiments showed that the oxidation of linoleate occurs in two discrete steps, since the cleavage of the C12-H bond is very sensitive to isotopic substitution (k(H)/k(D) = 14.6 +/- 3.0) while a minimal isotope effect (k(H)/k(D) = 1.25 +/- 0.08) was observed for the C13-H bond breaking step. These data suggest that crepenynic acid is produced via initial H-atom abstraction at C12 of a linoleoyl substrate. The relationship between the mechanism of enzymatic acetylenation and epoxidation is discussed.

Enantioselective total syntheses of (+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enone

The enantioselective total syntheses of (+)-decursin ( 1 ) and related natural dihydropyranocoumarins (−)-prantschimgin ( 3 ), (+)-decursinol ( 4 ), and (+)-marmesin ( 5 ) were achieved for the first time using catalytic asymmetric epoxidation of an enone as the key step. Catalytic asymmetric epoxidation of the enone was effectively promoted by the novel multifunctional asymmetric catalyst generated from La(O- i-Pr) 3, BINOL, and Ph 3AsO in a 1:1:1 ratio to afford epoxide in 94% yield and 96% ee, which was recrystallized to give optically pure epoxide. After conversion to the common key intermediate (−)-peucedanol ( 7 ), all natural dihydropyranocoumarins were synthesized through palladium-catalyzed intramolecular C–O coupling reactions. A possible reaction mechanism of the catalytic asymmetric epoxidation of enones is also described based on X-ray analysis, laser desorption/ionization time-of-flight mass spectrometry, kinetic studies, and asymmetric amplification studies.

Molybdenum complex-catalysed epoxidation of unsaturated fatty acids by organic hydroperoxides

The catalytic activity of the molybdenum catalysts, molybdenum naphthenate, Mo(CO) 6, H 2[Mo 2O 4(ox) 2(H 2O) 2]·4H 2O·Me 2CO, Mo(O) 2(acac) 2, and [Mo(O) 2(SAP)(EtOH)], was investigated in the reaction of oleic acid epoxidation by organic hydroperoxides. A new highly efficient and selective system for the epoxidation of unsaturated aliphatic acids was developed with tert-butyl hydroperoxide ( t-BuOOH) and the [Mo(O) 2(SAP)(EtOH)] complex. The epoxidation reaction of oleic acid shows 86.8% selectivity to 9,10-epoxystearic acid at 67% conversion of t-BuOOH. Routine kinetic measurements were performed to determine the reaction orders with respect to t-BuOOH and the catalyst. They are 1.00±0.05 and 0.51±0.05, respectively. The activation energy and enthalpy, E a=99±4 kJ mol −1 and Δ H=96±4 kJ mol −1, were calculated from the temperature dependences. The results allowed us to propose a reaction mechanism whose outline is consistent with the generally accepted mechanism of the catalytic epoxidation of olefins by organic hydroperoxides.