Are peroxyformic acid and dioxirane electrophilic or nucleophilic oxidants?

The electronic character of peroxyformic acid and dioxirane has been clarified by the analysis of donor-acceptor interactions in 16 transition states (TS) for the epoxidation of olefins. Is has been shown that the olefins are attacked by peroxyformic acid (PFA) in an electrophilic way. A relation of the electronic character to reactivity has been found: the more electrophilic the attack on the C=C bond is, the faster the reaction. In contrast, dioxirane (DO) has been identified as both an electrophilic and nucleophilic oxidant, depending on the substituents at the C=C double bond. The substrates with electron-withdrawing groups are attacked by DO in a nucleophilic way. These reactions have comparably low activation barriers. For instance, the acrylonitrile epoxidation with dioxirane is significantly faster than the corresponding reaction with PFA and proceeds via a transition state with a smaller extent of reaction and a larger extent of asymmetry.     

Selective hydroxylation of methane by dioxiranes under mild conditions

The direct conversion of methane to methanol at low temperatures was achieved selectively using dioxiranes 1a,b either in the isolated form or generated in situ from aqueous potassium caroate and the parent ketone at a pH close to neutrality. Results suggest that the more powerful dioxirane TFDO (1b) should be the oxidant of choice.     

Oxygen Transfer from Inorganic and Organic Peroxides to Organic Substrates: A Common Mechanism?

In this progress report an attempt is made to rationalize, from a mechanistic point of view, the different ways in which oxygen is transferred from inorganic and organic peroxides to nucleophilic substrates, particularly olefins. Oxygen transfer from transition-metal peroxides, which is relevant to catalytic oxidations using O₂, H₂O₂ or ROOH, occurs via a cyclic or “pseudocyclic” peroxymetalation in which a dioxametallacycle is formed. Owing to the wide discrepancy between peroxymetalation and the conventional oxidation mechanism, i.e. nucleophilic attack of the substrate at the electrophilic “active oxygen”, we propose an alternative mechanism involving dioxiranes as the reactive species. The generation of dioxiranes appears to be a common denominator in the reactions of most organic peroxides e.g. peroxy acids, the reaction of electrophilic ketones with H₂O₂, or ozonizations. Oxygen transfer from dioxirane reagents probably involves the formation of a charge-transfer π-complex between the substrate and the carbon atom of the dioxirane, and the subsequent formation of a cyclic peroxidic intermediate.     

-Fluoro decalones as chiral epoxidation catalysts: fluorine effect

Three rigid monofluorinated trans-decalones 4a, 5e, and 6e (90% ee) have been synthesized from commercially available (−)-(R)-methyl naphthalenone (90% ee). Their structures have been fully characterized (NMR, X-ray): ketones 4a and 5e are Me,F-disubstituted to the carbonyl with the fluorine axial and equatorial, respectively, while ketone 6e is F-monosubstituted to the carbonyl with the fluorine equatorial. The use of these ketones as chiral catalysts for the epoxidation of trans-olefins (such as stilbene, β-methylstyrene and p-methoxy cinnamate) through the formation of dioxiranes shows (i) that dioxiranes with an equatorial fluorine to the dioxirane ring are less reactive and provide lower ee’s than dioxiranes with an axial fluorine and having the same chirality and (ii) that an axial methyl to the dioxirane ring is significantly less efficient than a fluorine. The results corroborate Armstrong and Houk’s theoretical model and our first hypothesis to rationalize the inverted enantioselectivities observed using -fluorinated cyclohexanones having the same chirality, i.e.: rapid ring inversion (Curtin–Hammett principle) allows the dioxirane conformation to have the fluorine axial (even if less populated than the other) to contribute significantly to the epoxidation reaction.     

Effect of geminal substitution on the strain energy of dioxiranes. Origin of the low ring strain of dimethyldioxirane

The strain energies (SE) for dioxirane (DO) dimethyldioxirane (DMDO) and related dioxiranes have been examined by several methods using high-level computational schemes (G2, G2(MP2), CBS-Q). A series of calculated O-O, C-O, and O-H bond dissociation energies (G2) point to special problems associated with classical homodesmotic reactions involving peroxides. The relative SEs of DO, DMDO, methyl(trifluoromethyl)dioxirane (TFDO), and difluorodioxirane (DFDO) have been estimated by combination of the dioxirane with cyclopropane to form the corresponding 1,3-dioxacyclohexane. The relative SE predicted for DMDO (2) is 7 kcal/mol lower than that of DO, while the SE of 1,1-difluorodioxirane (4) is 8 kcal/mol higher. The most reactive dioxirane, methyl (trifluoromethyl)dioxirane (3), has an estimated SE just 1 kcal/mol greater than that of DO but 8 kcal/mol greater than that of DMDO. Six independent methods support the proposed SE for DO of 18 kcal/mol. The SE of the parent dioxirane (DO) has been estimated relative to six-membered ring reference compounds by dimerization of dioxirane and or its combination with cyclopropane. The relative SE of cyclic hydrocarbons, ethers and peroxides have been predicted by the insertion/extrusion of -CH(2)- and -O- fragments into their respective lower and next higher homologues. The moderated SE of DMDO (approximately equal to 11 kcal/mol) has also been estimated on the basis of group equivalent reactions. The unusual thermodynamic stability of DMDO is largely a consequence of combined geminal dimethyl and dioxa substitution effects and its associated strong C-H bonds and C-CH(3) bonds. The data clearly demonstrate that the reference compounds used to estimate the SE for highly substituted small ring cyclic compounds should reflect their molecular architecture having the same substitutents on carbon.     

Relative reactivity of peracids versus dioxiranes (DMDO and TFDO) in the epoxidation of alkenes. A combined experimental and theoretical analysis

Comparative analysis of the calculated gas-phase activation barriers (DeltaE++) for the epoxidation of ethylene with dimethyldioxirane (DMDO) and peroxyformic acid (PFA) [15.2 and 16.4 kcal/mol at QCISD(T)// QCISD/6-31+G(d,p)] and E-2-butene [14.3 and 13.2 kcal/mol at QCISD(T)/6-31G(d)//B3LYP/6-311+G(3df,2p)] suggests similar oxygen atom donor capacities for both oxidants. Competition experiments in CH(2)Cl(2) solvent reveal that DMDO reacts with cyclohexene much faster than peracetic acid/acetic acid under scrupulously dried conditions. The rate of DMDO epoxidation is catalyzed by acetic acid with a reduction in the classical activation barrier of 8 kcal/mol. In many cases, the observed increase in the rate for DMDO epoxidation in solution may be attributed to well-established solvent and hydrogen-bonding effects. This predicted epoxidative reactivity for DMDO is not consistent with what has generally been presumed for a highly strained cyclic peroxide. The strain energy (SE) of DMDO has been reassessed and its moderated value (about 11 kcal/mol) is now more consistent with its inherent gas-phase reactivity toward alkenes in the epoxidation reaction. The unusual thermodynamic stability of DMDO is largely a consequence of the combined geminal dimethyl- and dioxa-substitution effects and unusually strong C-H and C-CH(3) bonds. Methyl(trifluoromethyl)dioxirane (TFDO) exhibits much lower calculated activation barriers than DMDO in the epoxidation reaction (the average DeltaDeltaE++ values are about 7.5 kcal/mol). The rate increase relative to DMDO of approximately 10(5), while consistent with the higher strain energy for TFDO (SE approximately 19 kcal/mol) is attributed largely to the inductive effect of the CF(3) group. We have also examined the effect of alkene strain on the rate of epoxidation with PFA. The epoxidation barriers are only slightly higher for the strained alkenes cyclopropene (DeltaE++ = 14.5 kcal/mol) and cyclobutene (DeltaE++ = 13.7 kcal/mol) than for cyclopentene (DeltaE++ = 12.1 kcal/mol), reflecting the fact there is little relief of strain in the transition state. Alkenes strained by twist or pi-bond torsion do exhibit much lower activation barriers.     

α-Fluoro decalones as chiral epoxidation catalysts: fluorine effect

Three rigid monofluorinated trans-decalones 4a, 5e, and 6e (90% ee) have been synthesized from commercially available (−)-(R)-methyl naphthalenone (90% ee). Their structures have been fully characterized (NMR, X-ray): ketones 4a and 5e are Me,F-disubstituted α to the carbonyl with the fluorine axial and equatorial, respectively, while ketone 6e is F-monosubstituted α to the carbonyl with the fluorine equatorial. The use of these ketones as chiral catalysts for the epoxidation of trans-olefins (such as stilbene, β-methylstyrene and p-methoxy cinnamate) through the formation of dioxiranes shows (i) that dioxiranes with an equatorial fluorine α to the dioxirane ring are less reactive and provide lower ee’s than dioxiranes with an axial fluorine and having the same chirality and (ii) that an axial methyl α to the dioxirane ring is significantly less efficient than a fluorine. The results corroborate Armstrong and Houk’s theoretical model and our first hypothesis to rationalize the inverted enantioselectivities observed using α-fluorinated cyclohexanones having the same chirality, i.e.: rapid ring inversion (Curtin–Hammett principle) allows the dioxirane conformation to have the fluorine axial (even if less populated than the other) to contribute significantly to the epoxidation reaction.     

二氧杂环丙烷参与的烯烃环氧化反应

酮是催化烯烃环氧化反应的一类重要催化剂, 酮与氧化剂KHSO₅ (Oxone)可原位产生二氧杂环丙烷中间体, 然后二氧杂环丙烷中间体将氧原子传递给烯烃使之成为环氧化物, 而自身又生成原来的酮. 酮的催化效能大小与酮产生二氧杂环丙烷的能力、二氧杂环丙烷将氧原子传给烯烃的能力以及反应条件下酮的稳定性有关. 本工作对各种脂肪酮、脂环酮、杂环酮对烯烃环氧化催化能力的大小及其影响因素进行了评述.     

Mechanism of the oxidation of sulfides by dioxiranes. 1. Intermediacy of a 10-S-4 hypervalent sulfur adduct

Earlier studies established that dimethyldioxirane (1a) reacts with sulfides 2 in two consecutive concerted electrophilic oxygen-transfer steps to give first sulfoxides 3 and then sulfones 4. The same sequential electrophilic oxidation model was assumed for the reaction of sulfides 2 with the strongly electrophilic methyl(trifluoromethyl)dioxirane (1b). In this paper we report on a systematic and general study on the mechanism of the reaction of simple sulfides 2 with DMDO (1a) and TFDO (1b) which provides clear evidence for the involvement of hypervalent sulfur species in the oxidation process. In the oxidation of sulfides 2a-c, diphenyl sulfide (2d), para-substituted aryl methyl sulfides 2e-i, and phenothiazine 2k with 1b, the major product was the corresponding sulfone 4, even when a 10-fold excess of sulfide relative to 1b was used. The sulfone:sulfoxide 4:3 ratio depends among other factors on the dioxirane 1a or 1b used, the sulfide substitution pattern, the polar, protic, or aprotic character of the solvent, and the temperature. The influence of these factors and also deuterium and (18)O tracer experiments performed allow a general mechanism to be depicted for these oxidations in which the key step is the reversible cyclization of a zwitterionic intermediate, 6, to form a hypervalent sulfur species, 7. The classical sequential mechanism which establishes that sulfides are oxidized first to sulfides and then to sulfones can be enclosed in our general picture of the process and represents just those particular cases in which the zwitterionic intermediate 6 decomposes prior to undergoing ring closure to afford the hypervalent sulfurane intermediate 7.     

Epoxidation by sodium chlorite with aldehyde-promoted chlorine dioxide formation

An improved method is described for selective room temperature epoxidation of alkenes by sodium chlorite in a solvent mixture of ethanol, acetonitrile, and water buffered at pH 7. In addition, the use of aldehydes as promoters in chlorite oxidations is described for the first time. The amount of sodium chlorite, the solvent mixture, and the addition of formaldehyde as a practical promoter were optimized. Styrene was used as a test substrate in the optimization studies and the generality of the method was assessed by using a variety of nucleophilic and electrophilic substrates. Yields up to 89% were obtained with styrene and other nucleophilic alkenes are readily converted into epoxides.     

Predicting efficient C(60) epoxidation and viable multiple oxide formation by theoretical study

The epoxidation of C(60) by various oxidizing agents such as dimethyldioxirane (DMD), methyl(trifluoromethyl)dioxirane (MTMD), and bis(trifluoromethyl)dioxirane (BTMD) has been probed computationally by the AM1 method. The computations have revealed that for the reaction forming C(60)O through a concerted "spiro" transition state, the currently used DMD involves its HOMO lone-pair and the LUMO (pi) of fullerene in an inverse electron demand fashion. This is distinct from the DMD reaction with ethylene. On the other hand, the addition of CF(3) groups lowers the LUMO (peroxide sigma) of MTMD and BTMD by virtue of negative hyperconjugation; the oxidants can then attack the fullerene nucleophilically at an increased rate to the maximum extent. These estimations have thus established that the strong electrophilic oxidizing agents remarkably enhance the fullerene epoxidation. DMD further produces C(60)O(2) and C(60)O(3) via multiple epoxidations, as C(60)O might best be produced quantitatively by MTMD and BTMD. The regiochemistry of the multiple oxidation products in which the subsequent oxidations take place at the adjacent sites is consistent with the increased nucleophilicity of the nearest double bonds attached to the prevailing epoxide function.     

Poly(ethylene glycol)-supported α,α,α-trifluoroacetophenone in dioxirane mediated alkene epoxidation reactions

Poly(ethylene glycol) (PEG) was used for the immobilization of α,α,α-trifluoroacetophenone and the utility of this supported ketone has been examined in dioxirane mediated epoxidation of alkenes. The PEG-ketone reagent was found to be an effective homogeneous catalyst for the epoxidation of a variety of alkenes in the presence of Oxone^® and was readily recovered from the reaction mixtures and reused.     

Aldehyde-catalyzed epoxidation of unactivated alkenes with aqueous hydrogen peroxide

The organocatalytic epoxidation of unactivated alkenes using aqueous hydrogen peroxide provides various indispensable products and intermediates in a sustainable manner. While formyl functionalities typically undergo irreversible oxidations when activating an oxidant, an atropisomeric two-axis aldehyde capable of catalytic turnover was identified for high-yielding epoxidations of cyclic and acyclic alkenes. The relative configuration of the stereogenic axes of the catalyst and the resulting proximity of the aldehyde and backbone residues resulted in high catalytic efficiencies. Mechanistic studies support a non-radical alkene oxidation by an aldehyde-derived dioxirane intermediate generated from hydrogen peroxide through the Payne and Criegee intermediates.

An atropisomeric two-axis aldehyde is capable of catalysing the organocatalytic epoxidation of unactivated alkenes using hydrogen peroxide as the oxidant.     

Enantioselective epoxidation of alkenes catalyzed by 2-fluoro-N-carbethoxytropinone and related tropinone derivatives

Several alpha-substituted N-carbethoxytropinones have been evaluated as catalysts for asymmetric epoxidation of alkenes with Oxone, via a dioxirane intermediate. alpha-Fluoro-N-carbethoxytropinone (2) has been studied in detail and is an efficient catalyst which does not suffer from Baeyer-Villiger decomposition and can be used in relatively low loadings. This ketone was prepared in enantiomerically pure form using chiral base desymmetrization of N-carbethoxytropinone. Asymmetric epoxidation catalyzed by 2 affords epoxides with up to 83% ee. Among other derivatives tested, the alpha-acetoxy derivative 7 affords the highest enantioselectivities.     

Molecule-induced homolysis of N-hydroxyphthalimide (NHPI) by peracids and dioxirane. A new, simple, selective aerobic radical epoxidation of alkenes

Evidences are reported concerning the molecule-induced homolysis of NHPI by peracids and dioxirane; their combination can be utilized for the aerobic free-radical epoxidation of alkenes with selectivity quite different from the well-known epoxidation by peracids.     

Regioselectivity and diasteroselectivity in Pt(II)-mediated "green" catalytic epoxidation of terminal alkenes with hydrogen peroxide: mechanistic insight into a peculiar substrate selectivity

Recently developed electron-poor Pt(II) catalyst 1 with the "green" oxidant 35% hydrogen peroxide displays high activity and complete substrate selectivity in the epoxidation of terminal alkenes because of stringent steric and electronic requirements. In the presence of isolated dienes bearing terminal and internal double bonds, epoxidation is completely regioselective toward the production of terminal epoxides. Insight into the mechanism is gained by means of a reaction progress kinetic analysis approach that underlines the peculiar role of 1 in activating both the alkene and H2O2 in the rate-determining step providing a rare example of nucleophilic oxidation of alkenes by H2O2.     

Theory of chemical bonds in metalloenzymes XII: Electronic and spin structures of metallo–oxo and isoelectronic species and spin crossover phenomena in oxygenation reactions

The broken-symmetry (BS) and multideterminant approaches to atomic oxygen (O), molecular oxygen (O₂) and iron–oxo (Fe(IV)O) core in P450 have elucidated electronic structures of the ground triplet and excited singlet states, which indicate isoelectronic characteristics of the species. The dissociation processes of the O–O and Fe–O double bonds are also examined to clarify the radical character, namely O-atom property responsible for radical mechanism of hydroxylations of alkanes and epoxidation of alkenes. This isolobal analogy has indeed enabled us to propose possible reaction mechanisms of oxygenation reactions by the Fe(IV)O species on the basis of available theoretical and experimental results for O and O₂. Similarly, an isolobal analogy of the σ^* bond among Fe(IV)O, dioxirane, peracids, etc. indicates the common electrophilic property for the oxygenation reactions. The small energy gaps between the high- and low-spin states of the transition structures and intermediates generated in the oxygenation reactions are found to be origins for spin crossover phenomena along the reaction pathways of these reactions.     

Direct Oxidation of Csp3−H bonds using in Situ Generated Trifluoromethylated Dioxirane in Flow

A fast, scalable, and safer C_sp³−H oxidation of activated and un-activated aliphatic chains can be enabled by methyl(trifluoromethyl)dioxirane (TFDO). The continuous flow platform allows the in situ generation of TFDO gas and its rapid reactivity toward tertiary and benzylic Csp³−H bonds. The process exhibits a broad scope and good functional group compatibility (28 examples, 8–99 %). The scalability of this methodology is demonstrated on 2.5 g scale oxidation of adamantane.     

Mechanism of [gamma-H2SiV2W10O40](4-)-catalyzed epoxidation of alkenes with hydrogen peroxide

The mechanism of [gamma-H2SiV2W10O40]4--catalyzed epoxidation of alkenes with hydrogen peroxide in acetonitrile/tert-butyl alcohol was investigated. The negative Hammett rho+ (-0.88) for the competitive oxidation of p-substituted styrenes and the low XSO (XSO = (nucleophilic oxidation)/(total oxidation)) value of <0.01 for the [gamma-H2SiV2W10O40]4--catalyzed oxidation of thianthrene-5-oxide reveal that the strong electrophilic oxidant species is formed on [gamma-H2SiV2W10O40]4- (I). The preferable formation of trans-epoxide for the epoxidation of 3-substituted cyclohexenes shows the steric constraints of the active oxidant on I. The 51V NMR, 183W NMR, and CSI-MS spectroscopy show that the reaction of I with hydrogen peroxide leads to the reversible formation of a hydroperoxo species [gamma-HSiV2W10O39OOH]4- (II). The successive dehydration of II forms III, which possibly has an active oxygen species of a mu-eta2:eta2-peroxo group. The kinetic and spectroscopic studies show that the present epoxidation proceeds via III. The energy diagram of the epoxidation with density functional theory (DFT) supports the idea.     

Selective synthesis of hydroxy analogues of valinomycin using dioxiranes

A synthesis of representative monohydroxy derivatives of valinomycin (VLM) was achieved under mild conditions by direct hydroxylation at the side chains of the macrocyclic substrate using dioxiranes. Results demonstrate that the powerful methyl(trifluoromethyl)dioxirane 1b should be the reagent of choice to carry out these key transformations. Thus, a mixture of compounds derived from the direct dioxirane attack at the β-(CH(3))(2)C-H alkyl chain of one Hyi residue (compound 3a) or of one Val moiety (compounds 3b and 3c) could be obtained. Following convenient mixture separation, each of the new oxyfunctionalized macrocycles became completely characterized.