[70197-13-6]  · CH3O3Re  · (MW 250)

(catalyst in the hydrogen peroxide oxidation of numerous compounds, including the well-studied epoxidation of alkenes.5 Catalyzes 1,3-allylic transpositions,6 the metathesis of alkenes7,8 and aldehyde olefination9,10)

Physical Data: thermally stable white solid, mp 111 °C. Hydrolyzed rapidly in basic aqueous solutions but much slower in acidic solutions. Deactivated under photolysis conditions.

Solubility: highly soluble in virtually any solvent from pentane to water.

Form Supplied in: commercially available from Aldrich and Fluka.

Epoxidation of Alkenes5

In 1991, Hermann demonstrated that alkenes are efficiently converted to the corresponding epoxide using methyltrioxorhenium (MTO) as the catalyst and hydrogen peroxide as the co-oxidant.11 A range of alkenes undergo epoxidation at ambient temperatures with a catalyst loading of 0.1 to 1 mol% (1).

However, serious limitations of the original procedure included ring opening or oxidative cleavage of the newly formed epoxide, a consequence of the acidic nature of the rhenium catalyst (2).

The addition of tertiary amines, usually pyridine, has been found to be successful in both suppressing such side reactions and substantially increasing the rate of epoxidation.12 The reaction is remarkably general for efficient epoxidation of a number of alkenes (3-6).

It must be stressed that the amount of amine added to the MTO-catalyzed epoxidation reaction is critical. The addition of tertiary amines was found to significantly inhibit catalyst activity at low concentrations. Studies have shown that the lifetime of the catalyst is intrinsically linked to the amount of pyridine present and concentrations of 3 mol% or more of pyridine in nitromethane or dichloromethane are required for high conversions of alkenes. An example that highlights this not well-understood phenomena is the epoxidation of monoterpenes (7).13 A relatively high mol% of pyridine had to be employed in order to produce high yields. Even higher mol% of pyridine significantly decreased the yield. The tertiary amine additives are thought to play a crucial role in preventing decomposition of the epoxide products, prolonging the lifetime of the catalyst in solution and increasing the rate of epoxidation. An extensive amount of work on the equilibria and kinetics of amine additives in MTO-catalyzed epoxidation reactions has been undertaken.14

Other tertiary amines have been utilized in the MTO-catalyzed epoxidation reactions. Pyrazole was also found to be an effective additive for a variety of alkenes.15 The use of an equimolar amount of 3-cyanopyridine and pyridine as an additive for the epoxidation of terminal alkenes has been found to be high yielding with little-to-no destruction of the resulting epoxide detected.16,17 This system is effective for the epoxidation of a range of alkenes, in particular alkenes of relatively low reactivity (8-10). Electron deficient alkenes did not perform well under such epoxidation conditions.

A comparative study of the effectiveness of various amine additives has been undertaken (11-13).18

Although pyridine is less expensive than pyrazole, the latter seems to be more general. However, the choice of amine additive remains unclear when applying this methodology to new substrates and, although somewhat predictable, may be a matter of experimental trial and error.

Treatment of homo-allylic alcohols with catalytic MTO and hydrogen peroxide results in epoxidation followed by hydroxyl lactonization to yield substituted tetrahydrofurans in high yield (14).19 Alcohols, acids and esters all undergo such domino epoxidation/cyclization reactions.20

The epoxidation process has several distinct advantages over existing methodology. The epoxidation is carried out under neutral (non-acidic) conditions and does not suffer from unwanted side reactions. All the reagents used in the MTO-catalyzed epoxidation are easily handled and commercially available. In comparison, meta-chloroperbenzoic acid (m-CPBA) is only available as a mixture with the acid and cannot be purified safely due to its explosive nature. DMDO needs to be prepared and titrated directly prior to use.

Typical Procedure for the Epoxidation of Alkenes17

The alkene (10 mmol) was dissolved in dichloromethane (3 mL, 2 M concentration in alkene) to which the amine (1.2 mmol) and MTO (0.05 mmol) was added. Then 30% hydrogen peroxide (20 mmol) was added and the reaction vigorously stirred whereupon the solution turns yellow, indicative of the formation of the active catalyst. After 1h a catalytic amount of manganese oxide was added (to destroy any remaining peroxides in solution). When evolution of oxygen had stopped, the layers were separated, the aqueous layer extracted with dichloromethane (3 × 25 mL) and the combined organic extracts dried (Na2SO4) and concentrated under reduced pressure.

Other systems have been developed in the formation of acid-sensitive epoxides. Adam has developed an MTO-catalyzed epoxidation process using a urea/hydrogen peroxide (UHP) adduct.21 Although this methodology allows for the isolation of some acid-sensitive epoxides, other alkenes, such as a-methylstyrene, gave significant amounts of the corresponding 1,2-diols and yields in many cases were only modest.

Sodium percarbonate (the so-called ‘solid form’ of hydrogen peroxide) has been utilized in the MTO-catalyzed epoxidation.22 Although the use of sodium percarbonate offers no improvement in performance, it uses a safer and more easily handled co-oxidant that may prove to have application on an industrial scale. Trifluoroethanol has been used as the solvent in the MTO-catalyzed reaction of alkenes and has shown enhanced rates of epoxidation for a variety of alkenes at low catalyst loading (0.1 mol%).23 Unfortunately the lack of solubility of non-polar alkenes in such a fluorinated solvent remains a problem. Epoxidation of alkenes in an ionic liquid has been reported and the use of no organic solvents has possible industrial applications in a more eco-friendly process.24 A limitation of this process is once again the low solubility of certain alkenes in an ionic liquid. For example, 1-decene showed poor solubility in such a system which manifested itself in a modest yield of 46%. MTO has been supported on a silica tether allowing for epoxidation of alkenes under environmentally benign conditions.25 Although such a system has much promise the silica supported MTO has lower reactivity in comparison to its homogeneous partner.

Regio- and Diastereoselectivity

Unlike many other transition metal-catalyzed epoxidation reactions, little-to-no diastereoselectivity is usually detected in the MTO-catalyzed epoxidation of allylic alcohols.21,26 An extensive comparative study has been undertaken showing that metal alcoholate binding does not apply in MTO-catalyzed epoxidation reactions.27 This observation tends to suggest that a rhenium peroxo complex is the active oxidant. Computational experiments have demonstrated that the rhenium bis(peroxo) complex (probably the hydrated form) is the active species in the MTO-catalyzed epoxidation of propenol.28

Oxidation of Alkynes

The MTO/hydrogen peroxide oxidation of alkynes has been studied.29 Internal alkynes yield predominantly diketones (15), whilst terminal alkynes yield the corresponding acid or esters, depending on the solvent employed (16).

Baeyer-Villiger Oxidation

Oxidation of cyclic and acyclic ketones to the corresponding lactones and esters has been achieved. For example, cyclobutanone is converted to the corresponding lactone under the usual MTO/hydrogen peroxide conditions in almost quantitative yield in less than 1 h.30 The scope of this reaction has been explored.31 g-Butyrolactones were obtained in high yield and regioselectively by an MTO-catalyzed hydrogen peroxide Baeyer-Villiger oxidation (17).

Noteworthy is the chemoselectivity of the process - the oxidation can even be done in the presence of alkene moieties.

Aromatic Oxidation

The oxidation of aromatic groups to quinones is another facet of the MTO-catalyzed oxidation reactions with hydrogen peroxide and is of particular importance in the production of vitamin K3 (18).32 A highly acidic solution with a high concentration of hydrogen peroxide is essential. The reaction is both remarkably high yielding and selective.

An efficient synthesis of ortho- and para-benzoquinones of cardanol derivatives has been described using a similar oxidative process (19).33 Regioselectivity depends upon the nature and substitution pattern of the aromatic ring.

It has been shown that furan derivatives can be oxidized to the corresponding enediones using MTO and urea/hydrogen peroxide (20).34 Yields were high in all cases.

Oxidation of Sulfides

The MTO/hydrogen peroxide system effectively oxidizes sulfides to the corresponding sulfoxides (21).35,36

Further oxidation to the sulfone was found to be very slow in comparison to sulfide oxidation, and could be achieved on addition of a further equivalent of hydrogen peroxide. Thioketones have been oxidized in a similar fashion to yield ketones with expulsion of sulfur dioxide.37 Symmetrical disulfides have been oxidized to the corresponding thiosulfinates, thiosulfonates, and sulfonic acids.38

Oxidation of Silyl Compounds

MTO-catalyzed oxidization of silyl enol ethers with hydrogen peroxide yields a-hydroxyketones in high yield.39 The reactions were conducted with pyridine as the amine additive in acetic acid (22).

It is thought that the acid lowers the basicity of the solution increasing catalyst lifetime. The addition of acid alone resulted in total hydrolysis of the silyl-enol ether. Methyl trimethylsilyl ketene acetals undergo oxidation using the anhydrous MTO/UHP system,21 yielding a-hydroxyesters in high yield for a number of substrates (23).40

Oxidation of triorganosilanes to silanols has been achieved by treatment with MTO/UHP.41 High conversions and excellent selectivity over disiloxane products were obtained. Of particular interest is the transformation of an optically active silane to its corresponding silanol with almost complete retention configuration via oxidative insertion.41

Oxidation and Bromination of Alcohols

Although the oxidation of alcohols by hydrogen peroxide alone is negligible, catalytic amounts of bromide ions greatly enhance the rate of MTO-catalyzed oxidation of alcohols with hydrogen peroxide.42 Interestingly, a secondary alcohol has been selectively oxidized in the presence of a primary alcohol (24).42

Under similar conditions, acetylene and phenols were brominated in quantitative yields (25).42 In the case of the dibromination of acetylene derivatives E/Z selectivity was high at high bromide ion concentrations.

Oxidation of Phosphines, Arsenides, and Stannanes

Under standard MTO-catalyzed oxidation conditions with hydrogen peroxide, tertiary phosphines, triphenylarsine, and triphenylstibene were all efficiently oxidized.43 A detailed account of the rates of reactions of these oxidative processes has been reported which supports a mechanism that allows for nucleophilic attack of the substrate at the rhenium peroxide species.43

Oxidation of Nitrogen-Containing Compounds

Various substituted aniline derivatives have been oxidized under MTO/hydrogen peroxide conditions in good yield to the corresponding N-oxide derivatives (26).44

Nitrones are formed upon MTO/hydrogen peroxide oxidation of secondary amines (27).45

In the same manner, pyridine derivatives are oxidized to their respective N-oxides in good yield.46 Noteworthy is that N-oxidation, and not epoxidation, was observed when treating the substrates with MTO/hydrogen peroxide (28); non-conjugated systems under such oxidative systems gave epoxides in preference to N-oxidation (29). No degradation of the MTO catalyst was seen on N-oxidation, an observation that is not paralleled in the MTO-catalyzed epoxidation of alkenes.

N,N-Dimethyl hydrazones, derived from aldehydes, are efficiently oxidized to the corresponding nitriles in high yield (30).47,48 A number of examples have been reported.

Interestingly, hydrazones derived from ketones were found to yield the corresponding ketones (31).49

Oxidative Insertion

MTO has been found to catalyze oxidative insertion of remote C-H bonds in the presence of a large excess of hydrogen peroxide.50 This intriguing observation has been applied to a number of different hydrocarbons. Moreover, the reactions are stereospecific, as exemplified in the case of cis- and trans-decalin (32 and 33).

Dehydration, Amination, and Disproportionation of Alcohols

Ether formation, dehydration and disproportionation reactions catalyzed by MTO has been carried out.51 Yields were found to vary dramatically depending upon the substrate. These reactions have limited synthetic value and at present offer no advantages to existing technologies in each of these areas.

1,3-Allylic Transpositions

MTO is an effective catalyst in the isomerization of allylic alcohols. A variety of allylic alcohols have been tried and yields were generally high (34).6 Side reactions included condensation and dehydration of the product, processes that have been reported by the same group.6


MTO is active in alkene metathesis when activated by a co-catalyst such as S4N4/AlCl3, or supported on silica or alumina.7,8 In the original communication of Hermann et al.,7 the self-metathesis of allylic halides, silanes and unsaturated carboxylates and nitriles was achieved using MTO/Al2O3-SiO2 as the catalytic system (35).

At present, the metathesis reactivity of MTO has not been developed as a synthetically viable reagent in comparison to the well established Schrock and Grubb catalysts available.

Formation of Alkenes from Aldehydes

Treatment of various aldehydes with diazoalkenes and tertiary phosphines in the presence of MTO gave the corresponding coupled product in high yield.9,10 E/Z selectivity was low in most cases (36). An obvious advantage over Tebbe-Grubbs-type coupling reactions is that only a catalytic amount of the organometallic coupling reagent is required.

Cyclopropanation and Aziridination

MTO catalyzes both the reactions of ethyldiazoacetate and organic azides with alkenes and carbonyl compounds, respectively, to yield cyclopropanes in good yield.52 A number of examples of the cyclopropanation of alkenes have been reported under mild conditions (37 and 38). The reaction is remarkably general to differing steric and electronic environments of the alkene.

The analogous reaction with imines or carbonyl compounds results in the corresponding aziridines or epoxides respectively (39).52

MTO-catalyzed aziridination has also been achieved from alkenes utilizing [N-(p-tolylsulfonyl)imino]iodobenzene as the nitrene transfer reagent (40).53 Although yields at present are moderate to poor the reaction holds much promise for effective aziridination of alkenes.

Miscellaneous Reactions

MTO catalyses the formation of alkenes from epi-sulfides with triphenylphosphine (41).54 The reaction is general and high yielding at room temperature.

MTO also catalyzes the trimerization of aldehydes - one of the three oxygen atoms in the product is derived from MTO (42).55

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Andrew Hudson

Wayne State University, Detroit, Michigan, USA

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