Catalyzed Epoxidation

Metal-Catalyzed Epoxidation. Hydrogen peroxide is able to convert alkenes to epoxides in the presence of metal catalysts. Several metal oxides (Mo03, W03, Se02, V205) are known to catalyze such epoxidations.2,245,278,279 All these catalysts form stable inorganic peracids, and these peracids are supposedly involved in epoxidation in a process similar to organic peracids. 

Reactions with phase-transfer catalysis again proved to be efficient and synthetically valuable. Even the least reactive simple terminal alkenes are converted under mild conditions, in short reaction time to epoxides in high yields 283 

These reactions, however, have the disadvantage that H202 is usually employed in aqueous solution. It is known that water seriously retards epoxidation, and it may further transform the product epoxides to the corresponding 1,2-diols. This often results in low selectivity, which is the main reason why these reactions do not have the same broad synthetic utility as do epoxidations with alkyl hydroperoxides.245 285 

The use of alkyl hydroperoxides in the metal-catalyzed epoxidation of alkenes is their most important synthetic application. High-valence d° metals such as Mo(VI), W(VI), V(V), and Ti(IV) are the most effective catalysts 24 245,278,279,285,286 Used as soluble complexes or as heterogenized supported catalysts, they can give epoxides in near-quantitative yields. 

Because V(V) is a better oxidant, it exhibits low selectivity in the oxidation of simple nonsubstituted alkenes and is used mainly in the epoxidation of unsaturated alcohols, just as Ti(IV).244 

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In the Sharpless epoxidation of divinylmethanols only one of four possible stereoisomers is selectively formed. In this special case the diastereotopic face selectivity of the Shaipless reagent may result in diastereomeric by-products rather than the enantiomeric one, e.g., for the L -(-(-)-DIPT-catalyzed epoxidation of (E)-a-(l-propenyl)cyclohexaneraethanol to [S(S)-, [R(S)-, [S(R)- and [R(R)-trans]-arate constants is 971 19 6 4 (see above S.L. Schreiber, 1987). This effect may strongly enhance the e.e. in addition to the kinetic resolution effect mentioned above, which finally reduces further the amount of the enantiomer formed. 

Thallium-Catalyzed Epoxidation Process. The use of Tl(III) for olefin oxidation to yield glycols, carbonyls, or epoxides is weU known... 

Transition metal-catalyzed epoxidations, by peracids or peroxides, are complex and diverse in their reaction mechanisms (Section 5.05.4.2.2) (77MI50300). However, most advantageous conversions are possible using metal complexes. The use of t-butyl hydroperoxide with titanium tetraisopropoxide in the presence of tartrates gave asymmetric epoxides of 90-95% optical purity (80JA5974). 

Most recent publications by Hartshorn and his collaborators introduce a note of caution with regard to the mechanistic interpretation of results obtained in BF3-catalyzed epoxide cleavage reactions. They point out the marked dependence of the course of the reaction on the solvent used, either... 

The Jacobsen-Katsuki epoxidation reaction has found wide synthetic utility in both academia and industrial settings. As described previously, the majority of olefin classes, when conjugated, undergo Mn(salen)-catalyzed epoxidation in good enantioselectivity. In this section, more specific synthetic utilities are presented. 

The first asymmetric Mn(salen)-catalyzed epoxidation of silyl enol ethers was carried out by Reddy and Thornton in 1992. Results from the epoxidation of various silyl enol ethers gave the corresponding keto-alcohols in up to 62% ee Subsequently, Adam and Katsuki " independently optimized the protocol for these substrates yielding products in excellent enantioselectivity. 

Acid-catalyzed epoxide opening takes place by protonation of the epoxide to increase its reactivity, followed by nucleophilic addition of water. This nucleophilic addition is analogous to the final step of alkene bromination, in which a cyclic bromonium ion is opened by a nucleophile (Section 7.2). That is,... 

Alkenes are reduced by addition of H2 in the presence of a catalyst such as platinum or palladium to yield alkanes, a process called catalytic hydrogenation. Alkenes are also oxidized by reaction with a peroxyacid to give epoxides, which can be converted into lTans-l,2-diols by acid-catalyzed epoxide hydrolysis. The corresponding cis-l,2-diols can be made directly from alkenes by hydroxylation with 0s04. Alkenes can also be cleaved to produce carbonyl compounds by reaction with ozone, followed by reduction with zinc metal. 

The mechanisms of these acid-catalyzed epoxide openings are more complex than they at first appear. They seem to be neither purely SN1 nor SN2 but instead to be midway between the two extremes and to have characteristics of both. Take the reaction of 1,2-epoxy-l-methylcyclohexane with HBr shown in Figure 18.2, for instance. The reaction yields only a single stereoisomer of 2-bromo-2-methyl-cyclohexanol in which the —Br and —OH groups are trans, an S 2-li.ke result caused by backside displacement of the epoxide oxygen. But the fact that Br attacks the more hindered tertiary side of the epoxide rather than the less hindered secondary side is an SN1 -like result in which the more stable, tertiary carbocation is involved. 

Evidently, the transition state for acid-catalyzed epoxide opening has an Sn2 -like geometry but also has a large amount of S]v-l-like carbocationic character- Since the positive charge in the protonated epoxide is shared by the more highly substituted carbon atom, backside attack of Br- occurs at the more highly substituted site. 

Base-catalyzed epoxide opening is a typical S -2 reaction in which attack of the nucleophile takes place at the less hindered epoxide carbon. For example, 1,2-epoxypropane reacts with ethoxide ion exclusively at the less highly substituted, primary, carbon to give l-ethoxy-2-propanol. 

When the epoxide is to be used, a basic curing agent such as a tertiary amine, R3N, is added to cause the individual prepolymer chains to link together. This "cross-linking" of chains is simply a base-catalyzed epoxide... 

Oxidants Available for Selective Transition Metal-catalyzed Epoxidation... 

There are several available terminal oxidants for the transition metal-catalyzed epoxidation of olefins (Table 6.1). Typical oxidants compatible with most metal-based epoxidation systems are various alkyl hydroperoxides, hypochlorite, or iodo-sylbenzene. A problem associated with these oxidants is their low active oxygen content (Table 6.1), while there are further drawbacks with these oxidants from the point of view of the nature of the waste produced. Thus, from an environmental and economical perspective, molecular oxygen should be the preferred oxidant, because of its high active oxygen content and since no waste (or only water) is formed as a byproduct. One of the major limitations of the use of molecular oxygen as terminal oxidant for the formation of epoxides, however, is the poor product selectivity obtained in these processes [6]. Aerobic oxidations are often difficult to control and can sometimes result in combustion or in substrate overoxidation. In... 

While the titanium-catalyzed epoxidation reaction was flourishing, the pioneer version of the reaction remained undeveloped and it was not until 1999 that new... 

One problem associated with the peroxotungstate-catalyzed epoxidation system described above is the separation of the catalyst after the completed reaction. To overcome this obstacle, efforts to prepare heterogeneous tungstate catalysts have been conducted. De Vos and coworkers employed W catalysts derived from sodium tungstate and layered double hydroxides (LDH - coprecipitated MgCU, AICI3, and NaOH) for the epoxidation of simple olefins and allyl alcohols with... 

Table 6.6 Manganese/porphyrin-catalyzed epoxidation of cis-cy-dooctene with aqueous H2O2 (30%).

Table 6.7 Manganese sulfate-catalyzed epoxidation of olefins using aqueous H2O2 (30%).[al...

Table 6.9 MTO-catalyzed epoxidation of olefins with H202.

The use of various heterocyclic additives in the MTO-catalyzed epoxidation has been demonstrated to be of great importance for substrate conversion, as well as for the product selectivity. With regard to selectivity, the role of the additive is obviously to protect the product epoxides from deleterious, acid-catalyzed (Brons-ted or Lewis acid) ring-opening reactions. This can be achieved by direct coordination of the heterocyclic additive to the rhenium metal, thereby significantly decreasing its Lewis acidity. In addition, the basic nature of the additives will increase the pH of the reaction media. 

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