Molybdenum-catalyzed epoxidation

Molybdenum(VI) complexes are the most active catalysts for the epoxidation of unfunctionalized alkenes in the presence of hydroperoxides as oxygen donors, and many pnb-lished examples exist for molybdenum-catalyzed epoxidations. 

One molybdenum-catalyzed epoxidation, which is of indnstrial importance, needs special mention the Halcon process , which is the molybdennm-catalyzed epoxidation of propylene with TBHP or 1-phenylethyl hydroperoxide on a large scale (Scheme 74), and has been developed and patented by researchers from Halcon and Atlantic Richfield . 

TABLE 22. Comparison of the results of the molybdenum-catalyzed epoxidation of olefins... 

During the investigation of the molybdenum-catalyzed epoxidation of the allylic alcohol (43) mediated by a chiral (S)-proline derivative (44). S. Coleman-Kammula... 

While some molybdenum complexes such as Mo03(dien) were found to be inactive,236 the rates of molybdenum-catalyzed epoxidation of alkenes were found to be independent of the structure of the complex used, after an induction period representing the time for exchange of anionic ligands by the alkyl hydroperoxide. cis-Dioxomolybdenum(VI) diolates such as (78) were isolated... 

In another example, Chavali et al. demonstrated that 2D connectivity indices can give good structure/property correlations in molybdenum-catalyzed epoxidation [53,54]. They used the Computer Aided Molecular Design (CAMD) environment, a powerful computational tool used in product design. The method uses optimization techniques coupled with molecular design and property estimation methods, generating those molecular structures that match a desired set of properties. 

The retarding effect of alcohols on the rate of epoxidation manifests itself in the observed autoretardation by the alcohol coproduct.428,434 446,447 The extent of autoretardation is related to the ratio of the equilibrium constants for the formation of catalyst-hydroperoxide and catalyst-alcohol complexes. This ratio will vary with the metal. In metal-catalyzed epoxidations with fe/T-butyl hydroperoxide, autoretardation by tert-butyl alcohol increased in the order W < Mo < Ti < V the rates of Mo- and W-catalyzed epoxidations were only slightly affected. Severe autoretardation by the alcohol coproduct was also observed in vanadium-catalyzed epoxidations.428 434 446 447 The formation of strong catalyst-alcohol complexes explains the better catalytic properties of vanadium compared to molybdenum for the epoxidation of allylic alcohols.429 430 452 On the other hand, molybdenum-catalyzed epoxidations of simple olefins proceed approximately 102 times faster than those catalyzed by vanadium.434 447 Thus, the facile vanadium-catalyzed epoxidation of allyl alcohol with tert-butyl hydroperoxide may involve transfer of an oxygen from coordinated hydroperoxide to the double bond of allyl alcohol which is coordinated to the same metal atom,430 namely,... 

Species like 8.22 with V5+ as the metal ion has been isolated and characterized by X-ray studies (see Section 2.5.3). The reactivity of such complexes with alkenes has considerable similarities to the molybdenum-catalyzed epoxidation reaction. Kinetic studies with these model complexes indicate coordi-... 

In the molybdenum-catalyzed epoxidation of alkenes with /-butyl hydroperoxide what would be the effect of (a) Addition of external /-butanol in the reaction mixture (b) use of [Mo02(EG)2]2+ (EG = ethylene glycol) as the precatalyst rather than Mo(CO)6. 

Whereas peracids do not exhibit any face discriminating steric effect in the epoxidation of (S)-limoncne (Table 2, entries 3 and 4), due to the shallow topography of the molecule in the half-chair conformation (in accord with an MM2 simulation168), oxaziridine-mediated and molybdenum-catalyzed epoxidations (Table 2, entries 5 and 7 versus entries 1 and 2) show appreciable, but opposite, diastereoselectivity. 

The selectivity pattern of d° transition metal catalyzed epoxidations is much less readily understood. In the molybdenum-catalyzed epoxidation of (S)-limonene (Table 2, entries 1 and 2) the cis selectivity could perhaps be explained by a directing effect due to -coordinating of the second double bond to molybdenum. Such a selectivity is completely missing in the analogous tungsten-catalyzed reaction of (S)-limonene (Table 2, entry 4) in the absence of a second double bond as, for example, in 3/(-acetoxy-5-cholestene (Table 4) reactions with both metals afford similar diastereomeric ratios. 

The detailed mechanism of molybdenum-catalyzed epoxidation is still disputed 12. In the molybdenum hexacarbonyl catalyzed reaction it is probably the intact alkyl hydroperoxide that delivers the epoxide oxygen73. The active catalyst seems to incorporate the substrate74. As in the case of 3/i-acetoxy-5-cholestene (Table 4), selectivity for the sterically less congested /(-face increases with increasing bulk of the alkyl group. 

The high steric demand of the catalytically active species in molybdenum-catalyzed epoxidations is also demonstrated by the epoxidation of an estrene derivative 25 5-7 5. In contrast to the peracid epoxidation, and similar to epoxidation via halohydrin formation68, the molybdenum-catalyzed reaction shows a strong preference for the less hindered convex face of the olefinic system. 

Little is known about transition metal catalyzed epoxidation of simple allylic amides. The easily removable trichloroacetyl group is suitable as /V-substituent in the molybdenum-catalyzed epoxidation of (Z)-allylic systems with rm-butyl hydroperoxide, which produces the. sv -com-pound with appreciable selectivity21. 

FIGURE 1.12 Accepted alkylperoxo mechanism of molybdenum-catalyzed epoxidation with hydroperoxides. 

W. R. Thiel, T. Priermeier, The first olefin-substituted peroxomolybdenum complex Insight into a new mechanism for the molybdenum-catalyzed epoxidation of olefins, Angew. Chem. Int. Ed. Engl. 34 (1995) 1737. 

R. A. Sheldon, Molybdenum-catalyzed epoxidation of olefins with alkyl hydroperoxides. 

Many hydroxylated linalools [including compounds 105, 106, 108, and 110, both (Z)- and ( )-isomers], as well as the epoxides of both furanoid (109) and pyranoid (see section on pyrans) linalyl oxides, have been identified in papaya fruit (Carica papaya). At the same time, the first reported occurrence of die two linalool epoxides (112) in nature was made. These epoxides are well known to be unstable and easily cyclized (see Vol. 2, p. 165) and have been made by careful peracid oxidation of linalool. An interesting new method has now been described. While the vanadium- or titanium-catalyzed epoxidation of geraniol (25) gave the 2,3-epoxide (see above), as does molybdenum-catalyzed epoxidation with hydrogen peroxide, the epoxidation of linalool (28) with molybdenum or tungsten peroxo complexes and hydrogen peroxide led, by reaction on the 6,7-double bond, to 112. ... 

Limonene cfr-epoxide (549) is favored by employing molybdenum-catalyzed epoxidation of limonene, and it undergoes franj-diaxial opening with sodium phenylselenide. Both the ring-opened selenides were readily converted to trans-... 

The general trend is that metals which react via an oxometal pathway show a very similar behaviour using these two hydroperoxides as oxidant, e.g. the selenium catalyzed allylic oxidation of olefins to the corresponding a, p-unsaturated alcohols. Reactions which involve a peroxometal pathway, e.g. the molybdenum catalyzed epoxidations of olefins, show a completely different behaviour using these two hydroperoxides, namely virtually no reaction is observed with the bulky PHP. We conclude that PHP is a suitable mechanistic probe for distinguishing between oxometal and peroxometal pathways in catalytic oxidation. 

Previous studies indicated that the structure of the alkyl hydroperoxide in molybdenum catalyzed epoxidations has only a minor effect on the rate and selectivity [10]. Hence, we were initially surprised to observe that PHP failed to give the expected epoxidation of cyclohexene (1) and limonene (2) in the presence of a molybdenum catalyst (Tablel). Epoxidation of limonene with TBHP as oxidant, in contrast, gave the epoxide of the more highly substituted double bond in 84% selectivity, consistent with nucleophilic attack of the olefin on the alkylperoxomolybdenum(Vl) [3,5]. We tentatively concluded that this low reactivity of PHP is a result of steric hindrance in the putative alkylperoxomolybdenum(VI) intermediate. This prompted us to carry out a systematic investigation [8] of steric effects of the alkyl substituents in the alkyl hydroperoxide on the rate of molybdenum catalyzed epoxidations. 

Molybdenum-catalyzed epoxidations of cyclohexene under pseudo first-order reaction conditions showed the highest rate, of the investigated tertiary alkyl hydroperoxides (Figure 1), with TBHP. 

Table 1. Molybdenum catalyzed epoxidation with TBHP and PHP as oxidant...

Amides of lactic acid with secondary amines, e.g., 5 and 6, have been used as chiral ligands for the molybdenum-catalyzed epoxidation of alkenes (Section D.4.5.2.2.). They are easily obtained by aminolysis of the lactic esters4. 

Fig. 10. Molybdenum-catalyzed epoxidation of unsaturated fatty acid esters by alkyl hydroperoxides. Source Ref. 38.

More detailed studies of the oxidation of propylene [380, 381] and 1-octene [382] have shown that the actual rate equation is of the Michaelis-Menten type with the co-product alcohol being the competitive inhibitor. The fact that alcohols inhibit the molybdenum catalyzed epoxidation of olefins is well known [377, 378, 383]. In addition, it has been noted that induction periods are observed [378, 382] during which time the active catalyst, a molybdenum(VI) species [384, 379] is formed. 

The stereochemistry of molybdenum catalyzed epoxidation of olefins has been studied in some detail. Early work [375] indicated that ca-olefins give cn-epoxides and trans-olefins give trans-epoxides stereoselectively, equations (234) and (235). 

Reaction (241) was selective with very little hydroperoxide decomposition and appeared to obey a rate law which was first order in hydroperoxide, olefin and molybdenum complex similar to equation (227) [393]. A number of additional examples of molybdenum catalyzed epoxidation reactions in which a complexing group has directed the stereochemical course of the reaction have appeared in the literature [389,391,394,395], equations(242)-(247). 

Sheldon has determined the structure of the catalytic species in a number of molybdenum catalyzed epoxidation reactions [396]. It is interesting that the active catalytic species isolated from the reaction mixtures of the molybdenum-catalyzed epoxidations of a variety of different olefins with fer -butyl hydroperoxide were all... 

---