Sulfoxidation Of Thioethers Research Articles

Highly Selective Thioether Oxidation with H2O2 Catalyzed by Zr‐Substituted Keggin Phosphotungstate: Mechanistic Insights

AbstractThe Zr‐monosubstituted phosphotungstate (Bu4N)8[{PW11O39Zr(μ‐OH)(H2O)}2] (1) is a highly active and selective catalyst for thioether sulfoxidation with aqueous H2O2 in acetonitrile or acetonitrile/ethanol. The reaction proceeds unprecedentedly fast and completes within seconds at room temperature. Various sulfides produce corresponding sulfoxides with selectivity of 98–99 % and oxidant utilization efficiency of 92–99 %. The reaction mechanism was investigated using test substrates, kinetic, isotopic labeling, and spectroscopic tools. The oxidation of thianthrene‐5‐oxide and competitive sulfide‐sulfoxide oxidation point to an electrophilic oxidation mechanism, but a V‐shaped Hammett plot found for oxidation of p‐substituted thioanisoles may suggest a biphilic nature of active species. Kinetic studies revealed that the rate‐limiting step of the reaction is the interaction of a peroxo zirconium intermediate with organic substrates. ATR‐FT‐IR and 31P NMR spectroscopic studies coupled with stoichiometric experiments indicated that peroxo species capable of transferring an oxygen atom to thioethers are dimeric side‐on mono‐ and diperoxo complexes, [Zr2(μ‐η2 : η2‐O2){PW11O39}2(H2O)x]]8− (I) and [{Zr(μ‐η2‐O2)}2(PW11O39)2(H2O)y]10− (II), and monomeric Zr‐hydroperoxo [Zr(η2‐OOH)PW11O39]4− (III) and peroxo [Zr(η2‐O2)PW11O39]5− (IV) species, which dominate at high excess of H2O2. While I and III are endowed with electrophilic oxygen, which can be transferred to electron‐rich sulfides, more negatively charged II and IV preferably react with thioethers comprising electron‐withdrawing substituents.

Activation of H2O2 over Zr(IV). Insights from Model Studies on Zr-Monosubstituted Lindqvist Tungstates

Zr-monosubstituted Lindqvist-type polyoxometalates (Zr-POMs), (Bu4N)2[W5O18Zr(H2O)3] (1) and (Bu4N)6[{W5O18Zr(μ-OH)}2] (2), have been employed as molecular models to unravel the mechanism of hydrogen peroxide activation over Zr(IV) sites. Compounds 1 and 2 are hydrolytically stable and catalyze the epoxidation of C═C bonds in unfunctionalized alkenes and α,β-unsaturated ketones, as well as sulfoxidation of thioethers. Monomer 1 is more active than dimer 2. Acid additives greatly accelerate the oxygenation reactions and increase oxidant utilization efficiency up to >99%. Product distributions are indicative of a heterolytic oxygen transfer mechanism that involves electrophilic oxidizing species formed upon the interaction of Zr-POM and H2O2. The interaction of 1 and 2 with H2O2 and the resulting peroxo derivatives have been investigated by UV–vis, FTIR, Raman spectroscopy, HR-ESI-MS, and combined HPLC-ICP-atomic emission spectroscopy techniques. The interaction between an 17O-enriched dimer, (Bu4N)6[{W5O18Zr(μ-OCH3)}2] (2′), and H2O2 was also analyzed by 17O NMR spectroscopy. Combining these experimental studies with DFT calculations suggested the existence of dimeric peroxo species [(μ-η2:η2-O2){ZrW5O18}2]6– as well as monomeric Zr-hydroperoxo [W5O18Zr(η2-OOH)]3– and Zr-peroxo [HW5O18Zr(η2-O2)]3– species. Reactivity studies revealed that the dimeric peroxo is inert toward alkenes but is able to transfer oxygen atoms to thioethers, while the monomeric peroxo intermediate is capable of epoxidizing C═C bonds. DFT analysis of the reaction mechanism identifies the monomeric Zr-hydroperoxo intermediate as the real epoxidizing species and the corresponding α-oxygen transfer to the substrate as the rate-determining step. The calculations also showed that protonation of Zr-POM significantly reduces the free-energy barrier of the key oxygen-transfer step because of the greater electrophilicity of the catalyst and that dimeric species hampers the approach of alkene substrates due to steric repulsions reducing its reactivity. The improved performance of the Zr(IV) catalyst relative to Ti(IV) and Nb(V) catalysts is respectively due to a flexible coordination environment and a low tendency to form energy deep-well and low-reactive Zr-peroxo intermediates.

A heme•DNAzyme activated by hydrogen peroxide catalytically oxidizes thioethers by direct oxygen atom transfer rather than by a Compound I-like intermediate.

Hemin [Fe(III)-protoporphyrin IX] is known to bind tightly to single-stranded DNA and RNA molecules that fold into G-quadruplexes (GQ). Such complexes are strongly activated for oxidative catalysis. These heme•DNAzymes and ribozymes have found broad utility in bioanalytical and medicinal chemistry and have also been shown to occur within living cells. However, how a GQ is able to activate hemin is poorly understood. Herein, we report fast kinetic measurements (using stopped-flow UV–vis spectrophotometry) to identify the H2O2-generated activated heme species within a heme•DNAzyme that is active for the oxidation of a thioether substrate, dibenzothiophene (DBT). Singular value decomposition and global fitting analysis was used to analyze the kinetic data, with the results being consistent with the heme•DNAzyme's DBT oxidation being catalyzed by the initial Fe(III)heme–H2O2 complex. Such a complex has been predicted computationally to be a powerful oxidant for thioether substrates. In the heme•DNAzyme, the DNA GQ enhances both the kinetics of formation of the active intermediate as well as the oxidation step of DBT by the active intermediate. We show, using both stopped flow spectrophotometry and EPR measurements, that a classic Compound I is not observable during the catalytic cycle for thioether sulfoxidation.

Synthesis, structure and catalytic study of a new sandwiched-type vanadoselenite

A novel sandwiched-type vanadoselenite with the formula of K6H8[(SeV10O28(SeO3)3)2(Ni(H2O)4)]·24H2O (1) has been synthesized in aqueous medium and well characterized. Single crystal X-ray diffraction indicates that the sandwiched polyanion [(SeV10O28(SeO3)3)2(Ni(H2O)4)]14− consisted of two trivicant Keggin building units [SeV10O28(SeO3)3]8− and one interconnected Ni2+ ion. Experimental results demonstrated that it could serve as a heterogeneous catalyst for sulfoxidation of thioethers and performed effectively catalytic activity. Under the optimized reaction condition, methyl phenyl sulfoxide could be oxidized to methyl phenyl sulfones within 1 h by using 1 mmol of the substrate, 3 mmol of TBHP and 2 μmol of the catalyst 1 at 25 °C in methanol. Moreover, catalyst 1 can also be easily recycled and reused four times without obvious decrease of catalytic activity.

Carbon Nanotubes Modified by Venturello Complex as Highly Efficient Catalysts for Alkene and Thioethers Oxidation With Hydrogen Peroxide.

In this work, we elaborated heterogeneous catalysts on the basis of the Venturello complex [PO4{WO(O2)2}4]3− (PW4) and nitrogen-free or nitrogen-doped carbon nanotubes (CNTs or N-CNTs) for epoxidation of alkenes and sulfoxidation of thioethers with aqueous hydrogen peroxide. Catalysts PW4/CNTs and PW4/N-CNTs (1.8 at. % N) containing 5–15 wt. % of PW4 and differing in acidity have been prepared and characterized by elemental analysis, N2 adsorption, IR spectroscopy, HR-TEM, and HAADF-STEM. Studies by STEM in HAADF mode revealed a quasi-molecular dispersion of PW4 on the surface of CNTs. The addition of acid during the immobilization is not obligatory to ensure site isolation and strong binding of PW4 on the surface of CNTs, but it allows one to increase the PW4 loading and affects both catalytic activity and product selectivity. Catalytic performance of the supported PW4 catalysts was evaluated in H2O2-based oxidation of two model substrates, cyclooctene and methyl phenyl sulfide, under mild conditions (25–50°C). The best results in terms of activity and selectivity were obtained using PW4 immobilized on N-free CNTs in acetonitrile or dimethyl carbonate as solvents. Catalysts PW4/CNTs can be applied for selective oxidation of a wide range of alkenes and thioethers provided a balance between activity and selectivity of the catalyst is tuned by a careful control of the amount of acid added during the immobilization of PW4. Selectivity, conversion, and turnover frequencies achieved in epoxidations over PW4/CNTs catalysts are close to those reported in the literature for homogeneous systems based on PW4. IR spectroscopy confirmed the retention of the Venturello structure after use in the catalytic reactions. The elaborated catalysts are stable to metal leaching, show a truly heterogeneous nature of the catalysis, can be easily recovered by filtration, regenerated by washing and evacuation, and then reused several times without loss of the catalytic performance.

Rate and Selectivity Control in Thioether and Alkene Oxidation with H2O2 over Phosphonate‐Modified Niobium(V)–Silica Catalysts

AbstractSupported metal oxide catalysts are versatile materials for liquid‐phase oxidations, including alkene epoxidation and thioether sulfoxidation with H2O2. Periodic trends in H2O2 activation was recently demonstrated for alkene epoxidation, highlighting Nb‐SiO2 as a more active and selective catalyst than Ti‐SiO2. Three representative catalysts are studied consisting of NbV, TiIV, and ZrIV on silica, each made through a molecular precursor approach that yields highly dispersed oxide sites, for thioanisole oxidation by H2O2. Initial rates trend Nb>Ti≫Zr, as for epoxidation, and Nb outperforms Ti for a number of other thioethers. In contrast, selectivity to sulfoxide vs. sulfone trends Ti>Nb≫Zr at all conversions. Modifying the Nb‐SiO2 catalyst with phenylphosphonic acid does not completely remove sulfoxidation reactivity, as it did for photooxidation and epoxidation, and results in an unusual material active for sulfoxidation but neither epoxidation nor overoxidation to the sulfone.

Supramolecular Activation of Hydrogen Peroxide in the Selective Sulfoxidation of Thioethers by a Self‐Assembled Hexameric Capsule

AbstractAn efficient metal‐free organocatalytic activation of hydrogen peroxide (H2O2) towards thioethers leading to the corresponding sulfoxides in high yields at room temperature within hours was promoted by the hexameric capsule formed by the self‐assembly of resorcin[4]arene units. The capsule plays a dual role of activating the oxidant through hydrogen bonding and favouring the oxidation reaction inside the cavity. Inactivation of the supramolecular organocatalyst was observed by using competitive ammonium guests, mimicking the inactivation of enzymes by competitive inhibitors.magnified image

Polyoxomolybdate-Calix[4]arene Hybrid: A Catalyst for Sulfoxidation Reactions with Hydrogen Peroxide.

An easily accessible polyoxomolybdate-calix[4]arene hybrid 1 has been synthesized and applied as a heterogeneous catalyst in the sulfoxidation of thioethers to sulfoxides and to sulfones under strictly stoichiometric amounts of 30% H2O2 in CH3CN as the solvent. This study represents the first promising example of successful employment of calixarenes-polyoxometalate (POM) hybrid materials in the area of catalytic oxidations.

Selective Sulfoxidation of Thioethers and Thioaryl Boranes with Nitrate, Promoted by a Molybdenum–Copper Catalytic System

The catalytic reduction of nitrate by molybdo-enzymes plays a central role in the global biological cycle of nitrogen. However, the use of nitrates as oxidants in synthetic organic chemistry is very limited and typically requires very strong acidic and other extreme reaction conditions. We have developed a highly chemoselective and efficient catalytic process for the sulfoxidation of thioethers and arylthioethers containing boronic acid or boronic ester functional groups, using nitrate salts as oxidants. This homogeneous catalytic reaction was carried out in acetonitrile, where the MoO(2)Cl(2)(OPPh(3))(2) complex 1 or a mixture of complex 1 with Cu(NO(3))(2) were used as catalysts. We examined the reaction mechanism using (1)H, (15)N, and (31)P NMR techniques and (18)O-labeled sodium nitrate (NaN(18)O(3)) and show that the thioethers are oxidized by nitrate, generating nitrite. Our work adds to the existing chemical transformations available for organoboron compounds, providing straightforward accessibility to a variety of new substrates that could be suitable for Suzuki cross-coupling chemistry.

Haloperoxidase Activity of Oxovanadium(V) Thiobisphenolates

By employing the 2,2'-thiobis(2,4-di-tert-butylphenolate) ligand ((S)L(2-)) a novel oxovanadium(V) complex, (PPh(4))(2)[(S)LV(O)(μ(2)-O)(2)V(O)(S)L] (1), was synthesised that exhibits haloperoxidase activity: on addition of H(2)O(2) a sequence of successive peroxide formation and intramolecular thioether oxidation events (sulfoxide and sulfone) led to a mixture of five products, which were all identified unambiguously, partly through an independent synthesis and characterisation. It was shown that internal thioether oxidation proceeds through peroxide formation, but the sulfoxidation of external thioether functions requires further activation of the peroxide function by protons or alkyl cations. Consistently, the employment of tBuOOH instead of H(2)O(2) led to a very active system for the catalytic sulfoxidation of thioethers.

The Valence Bond Way: Reactivity Patterns of Cytochrome P450 Enzymes and Synthetic Analogs

The preceding decade has witnessed an immense surge of activity in the bioinorganic chemistry of transition metal enzymes and synthetic analogs that model their operation. The wide range of research covers both experimental and theoretical investigations of structure and reactivity patterns. Theory, and especially density functional theory (DFT), has become a very useful tool, an important partner of experiment in resolving structural and mechanistic issues. This flare of activity has generated a great deal of knowledge on intermediates, transition states, barriers, rate constants, rate-equilibrium relationships, stereoselectivity, and so forth. This abundance of acquired knowledge has created the need for establishing order, namely, the outlining of broad generalizations, as well as the creation of a more-intuitive interface between experimental and theoretical data. The valence bond (VB) diagram model, originally developed for organic reactions, is such a theoretical framework that has the potential to guide the requisite generalizations in the field of bioinorganic chemical reactivity. In this Account, we briefly describe the principles of construction of VB diagrams for bioinorganic reactions, detailing applications in the booming research area of heme enzyme (specifically cytochrome P450) reactivity, and particularly two archetypal reactions of these enzymes, alkane hydroxylation and thioether sulfoxidation. For congruence with the lingua franca of bioinorganic chemistry, the VB model is formulated to create bridges to (i) the molecular orbital (MO) description, (ii) the oxidation state formulation of transition metal complexes, and (iii) widely used concepts such as the Bell-Evans-Polanyi (BEP) principle. The VB diagram model reveals the origins of the barrier, describes the formation of transition states and reaction intermediates, and allows the prediction of barrier heights and structure-reactivity relationships. Thus, from the VB diagram model, we can rationalize the mechanistic selection during alkane hydroxylation compared with thioether sulfoxidation, as well as the different behaviors of the spin states during the reactions with the active species of P450, the high-valent iron oxo species called compound I (Cpd I). Furthermore, the VB model leads to expressions that enable us to estimate barrier heights from easily accessible reactant properties, such as bond energies, ionization potential, and electron affinities. We further show that the model is not limited to these archetypal processes: its applicability is wider and more general. Accordingly, we outline the potential applications of these principles to other reactions of P450 (such as olefin epoxidation and arene hydroxylation) and to similar reactions of nonheme enzymes and synthetic models. The VB diagram model leads to a unified understanding of complex bioinorganic transformations, creates order in the data, and provides an important framework for making useful predictions.

Valence bond modelling and density functional theory calculations of reactivity and mechanism of cytochrome P450 enzymes: thioether sulfoxidation

This paper introduces valence bond (VB) modelling of the mechanism and reactivity patterns of thioether sulfoxidation by cytochrome P450 enzymes (P450), as observed experimentally and as found computationally using DFT calculations on P450 sulfoxidation of para-(MeO, Me, H, NO2) substituted thioanisoles. Thus, this study addresses the fundamental factors that cause the following two mechanistic puzzles: (a) Why do sulfoxidation reactions by P450 prefer direct oxygen atom transfer, while at the same time, the observed reaction rates exhibit correlations with electron transfer properties, e.g. the redox potentials of the thioethers? (b) Why do these reactions exhibit spin-selective chemistry and proceed on the low spin doublet state, unlike alkane hydroxylation that proceeds via two-state reactivity on both doublet and quartet states? The first puzzle is reminiscent of the classical electron transfer–polar dichotomy in physical organic chemistry, while the second one is unique to the oxidative chemistry by metal–oxo reagents. The VB modelling shows that the doublet state sulfoxidation involves bond formation coupled electron transfer (BFCET), while the quartet state process involves, in addition, a coupled d-orbital excitation, thereby generating a higher barrier. Combined with the previous VB modelling of alkane hydroxylation by P450, the VB diagram model emerges as a conceptual tool that enables understanding of mechanistic puzzles and is capable of estimating barriers in a complex reaction system.

Vanadium-catalyzed, microwave-assisted oxidations with H2O2 in ionic liquids

The application of vanadium(V) catalysts in selective oxidation with peroxides offers an efficient procedure that is compatible with different functional groups and leads to good yields and selectivities. However, the search for more efficient and sustainable procedures that employ H2O2 as oxidant remains an important topic. In the last few years, striking results have been obtained by applying microwave (MW) activation in metal-catalyzed reactions carried out in ionic liquids (ILs). In the present study, results achieved with vanadium-based catalysts in oxidations of various substrates with H2O2 are presented; in particular, epoxidation of alkenes and sulfoxidation of thioethers have been investigated. Notably, in the latter oxidation, a significant improvement in the rate of reaction and an increase in selectivity have been observed in the case of hydrophobic ILs in combination with MW activation.

Characteristics of Mononuclear Ruthenium–Oxo Complexes Adjusted by Axial Ligand for the Catalysis of Oxygen-Transfer Reactions

Ruthenium(II) complexes, [Ru(babp)(dmso)L], consisting of tetradentate square-planar ligand (babp = 6,6′-bis(benzoylamino)-2,2′-bipyridinato) and two monodentate axial ones, DMSO and L (L = dmso or...

The role of crystalline structure of molybdenum oxide catalysts onto the activity and stability in sulfoxidation of thioethers

Sulfoxidation of 2-thiomethyl-4,6-dimethyl-pyrimidine and methyl-dodecyl-sulfure was carried out in liquid phase using H2O2 in dioxane (6 or 18 wt%) and several molybdenum and mixed antimony-molybdenum oxides such as: Mo8O23, MoO3-basal, MoO3-iSO, Sb2MoO6 and a mixture of Sb2Mo10O31, and Sb4Mo10O31 (SbxMo10O31) phases as catalysts. Both catalytic performances and catalysts stability (structural modifications and leaching) depended on characteristics of the structure. The less active catalysts exhibited a higher leaching. The most stable and thus active catalysts were those for which the leaching is compensated by structural changes going in the direction of the exacerbation of their crystallinity. In the investigated series the most effective were the Mo8O23 and Sb2MoO6. (c) 2007 Elsevier B.V. All rights reserved.

Asymmetric Sulfoxidation with Hydrogen Peroxide in Water

Water as a solvent provides perhaps the most ideal conditions pertaining to toxicity, environmental protection and cost. This paper describes the first sulfoxidation of thioethers with water as the solvent and uses the cost- and atom- economical hydrogen peroxide as the oxidant. A low platinum:BINAP catalyst loading (1 mol%) provides yields above 90%.

Asymmetric Sulfoxidation of Thioethers with Hydrogen Peroxide in Water Mediated by Platinum Chiral Catalyst

AbstractEasy stereoselective oxidation of prochiral aryl alkyl sulfides 2 to the corresponding sulfoxides can be achieved in water‐surfactant medium with inexpensive hydrogen peroxide mediated by the chiral platinum diphosphine complex {[(R)‐BINAP]Pt(μ‐OH)}2(BF4)2 (1). Remarkable key features of general interest are (i) easy isolation of the products from catalyst by simple diethyl ether/water‐surfactant two phase separation, (ii) catalyst loading as low as 1% mol, (iii) good yields, sulfoxide 3 to sulfone 4 ratio up to 200 : 1 and enantioselectivities up to 88%, (iv) mild experimental conditions.

In vitro sulfoxidation of thioether compounds by human cytochrome P450 and flavin-containing monooxygenase isoforms with particular reference to the CYP2C subfamily.

Cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes are major catalysts involved in the metabolism of xenobiotics. The sulfoxidation of the thioether pesticides, phorate, disulfoton, sulprofos, and methiocarb, was investigated. Using pooled human liver microsomes (HLMs), thioether compounds displayed similar affinities; however, phorate and disulfoton displayed higher intrinsic clearance rates than either sulprofos or methiocarb. The sulfoxidation of thioethers by HLMs was found to be predominantly P450-driven (85-90%) compared with FMO (10-15%). Among 16 cDNA-expressed human P450 isoforms and 3 human FMO isoforms examined, the following isoforms and their polymorphisms had the highest rates for sulfoxidation, as follows: phorate, CYP1A2, 3A4, 2B6, 2C9*1, 2C18, 2C19, 2D6*1, and FMO1; disulfoton, CYP1A2, 3A4, 2B6, 2C9*1, 2C9*2, 2C18, 2C19, 2D6*1, and FMO1; sulprofos, CYP1A1, 1A2, 3A4, 2C9*1, 2C9*2, 2C9*3, 2C18, 2C19, 2D6*1, and FMO1; methiocarb, CYP1A1, 1A2, 3A4, 2B6, 2C9*1, 2C19, 2D6*1, and FMO1. Among these isoforms, members of the CYP2C subfamily often had the highest affinities and clearance rates. Moreover, sulfaphenazole, a CYP2C9 competitive inhibitor, inhibited disulfoton sulfoxidation by CYP2C9 (IC50 0.84 microM) as well as in HLMs. Ticlopidine, a CYP2C19 mechanism-based inhibitor, inhibited disulfoton sulfoxidation by CYP2C19 (IC50 after coincubation, 43.5 microM; IC50 after preincubation, 4.3 microM) and also in HLMs. Our results indicate that current models of the substrate binding site of the CYP2C subfamily would not effectively predict thioether pesticide metabolism. Thus, the substrate specificity of CYP2Cs is more extensive than is currently believed, and some reevaluation of structure-activity relationships may be required.

A New Application of Layered Double Hydroxides as Solid Bases for the Sulfoxidation Reaction Activation.

The layered double hydroxides (LDHs) are able to promote the sulfoxidation of thioethers and thiophene derivatives with hydrogen peroxide in the presence of acetonitrile. The last serves both as reagent and solvent. The active species in the oxidation reaction is the peroxyimidic acid arising from the addition of hydrogen peroxide to acetonitrile promoted by LDH as base catalyst. The reactivity of sulfur compounds in the sulfoxidation reaction with H 2 O 2 is correlated to the nucleophilicity of the sulfur atom, so that diarylsulfides are more easily oxidized than dibenzothiophene. A competition between the sulfoxidation reaction and the direct decomposition of hydrogen peroxide has been observed.

Methyloxorhenium(V) complexes with two bidentate ligands: syntheses and reactivity studies.

Four new methyloxorhenium(V) complexes were synthesized: MeReO(PA)(2) (1), MeReO(HQ)(2) (2), MeReO(MQ)(2) (3), and MeReO(diphenylphosphinobenzoate)(2) (4) (in which PAH = 2-picolinic acid, HQH = 8-hydroxyquinoline, and MQH = 8-mercaptoquinoline). Although only one geometric structure has been identified crystallographically for 1, 2, and 3, two isomers of 3 and 4 in solution were detected by NMR spectroscopy. These compounds catalyze the sulfoxidation of thioethers by pyridine N-oxides and sulfoxides. The rate law for the reaction between pyridine N-oxides and thioethers, catalyzed by 1, shows a first-order dependence on the concentrations of pyridine N-oxide and 1. The second-order rate constants of a series of para-substituted pyridine N-oxides fall in the range of 0.27-7.5 L mol(-)(1) s(-)(1). Correlation of these rate constants by the Hammett LFER method gave a large negative reaction constant, rho = -5.2. The next and rapid step does not influence the kinetics, but it could be explored with competition experiments carried out with a pair of methyl aryl sulfides, MeSC(6)H(4)-p-Y. The value of each rate was expressed relative to the reference compound that has Y = H. A Hammett analysis of k(Y)/k(H) gave rho = -1.9. Oxygen-18 labeled 1 was used in a single turnover experiment for 4-picoline N-oxide and dimethyl sulfide. No (18)O-labeled DMSO was found. We suggest that the reaction proceeds by way of two intermediates that were not observed during the reaction. The first intermediate contains an opened PA-chelate ring; this allows the pyridine N-oxide to access the primary coordination sphere of rhenium. The second intermediate is a cis-dioxorhenium(VII) species, which the thioether then attacks. Oxygen-18 experiments were used to show that the two oxygens of this intermediate are not equivalent; only the new oxygen is attacked by, and transferred to, SR(2). Water inhibits the reaction because it hydrolyzes the rhenium(VII) intermediate.