Alkene epoxidation mediated

P-18 - A mechanistic exploration of alkene epoxidation mediated by H2O2 within porous titanosiiicate catalysts... 

The aerobic degradation of chloroethene (vinyl chloride) by Mycobacterium aurum strain LI proceeded by initial formation of an epoxide mediated by an alkene monooxygenase (Hartmans and de Bout 1992). This reaction has also been demonstrated to occur with Methylosinus trichosporium, even though subsequent reactions were purely chemical (Castro et al. 1992b). 

Mechanistic studies103 revealed that chiral ketone-mediated asymmetric epoxidation of hydroxyl alkenes is highly pH dependent. Lower enantioselectivity is obtained at lower pH values at high pH, epoxidation mediated by chiral ketone out-competes the racemic epoxidation, leading to higher enantioselectivity. (For another mechanistic study on ketone-mediated epoxidation of C=C bonds, see Miaskiewicz and Smith.104)... 

Nevertheless, Celia et al. have proved that employing MCPBA as secondary oxidant in TEMPO-mediated oxidations may have a number of advantages when a one-pot oxidation of an alcohol with a concurrent alkene epoxidation or a Baeyer-Villiger oxidation is desired.6 The use of MCPBA as a secondary oxidant in TEMPO-mediated alcohol oxidations was recently reviewed.7... 

Next, the scope of this C-glycosylation reaction was investigated. The NeuSAc chloride was found to serve as a donor in samarium mediated C-glycosylation, unfortunately, purification of C-glycoside from excess chloride donor is often problematic, making the NeuSAc phenyl sulfone the donor of choice. A variety of acceptors were also evaluated including alkenes, epoxides, vinyl esters, aldehydes and ketones. Only the aldehydes and ketones afforded the desired C-glycoside products. 

FIGURE 2.6 Mechanistic hypothesis for terminal alkene epoxidation with hydrogen peroxide mediated by lb on the basis of the results of reaction-progress kinetic analysis and P and F NMR studies. 

Trifluoromethyl ketones that are frequently used for mediating alkene epoxidation with dioxiranes are subject to degradation. A stabilized form is made by covalent anchoring to silica. ... 

Figure 7.10 Ordinary alkenes also undergo epoxidation mediated by MFO.These have little incentive to rearrange and so they generally serve as substrates for epoxide hydrolase to form vicinal diols. In this example the allylic group of the hypnotic agent secobarbital is epoxidized, but the epoxide is not observed among the isolated metabolites. Instead it is the diol that is found as a major metabolite.

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

The above-mentioned important and impressive applications of titanocene mediated and catalyzed epoxide opening have been achieved by using the already classical 5-exo, 6-exo and 6-endo cyclizations with alkenes or alkynes as radical acceptors. Besides these achievements, the high chemoselectiv-ity of radical generation and slow reduction of the intermediate radicals by Cp2TiCl has resulted in some remarkable novel methodology. 

Following the success with the titanium-mediated asymmetric epoxidation reactions of allylic alcohols, work was intensified to seek a similar general method that does not rely on allylic alcohols for substrate recognition. A particularly interesting challenge was the development of catalysts for enantioselective oxidation of unfunctionalized olefins. These alkenes cannot form conformationally restricted chelate complexes, and consequently the differentiation of the enan-tiotropic sides of the substrate is considerably more difficult. 

The oxidative cyclization of vinylallenes need not be directed by a pendant hydroxyl group in order to succeed. The higher reactivity of the allene compared with the exocyclic methylene group in 73 (Eq. 13.23) with monoperphthalic acid leads primarily to the allene oxide which rearranges to cydopentenone 74 [27]. Inevitably some epoxidation of the alkene also takes place during the reaction. When m-CPBA is used as the oxidant, another side reaction is associated with m-chlorobenzoic add-mediated decomposition of the intermediate epoxide. It is possible to overcome this problem by performing the epoxidation in dichloromethane in a two-phase system with aqueous bicarbonate so as to buffer the add [28]. 

The overall reaction catalyzed by epoxide hydrolases is the addition of a H20 molecule to an epoxide. Alkene oxides, thus, yield diols (Fig. 10.5), whereas arene oxides yield dihydrodiols (cf. Fig. 10.8). In earlier studies, it had been postulated that epoxide hydrolases act by enhancing the nucleo-philicity of a H20 molecule and directing it to attack an epoxide, as pictured in Fig. 10.5, a [59] [60], Further evidence such as the lack of incorporation of 180 from H2180 into the substrate, the isolation of an ester intermediate, and the effects of group-selective reagents and carefully designed inhibitors led to a more-elaborate model [59][61 - 67]. As pictured in Fig. 10.5,b, nucleophilic attack of the substrate is mediated by a carboxylate group in the catalytic site to form an ester intermediate. In a second step, an activated H20... 

Scheme 42 Epoxidation of alkenes with an Cr(V)-complex as mediator.

In recent years, dioxiranes have become workhorses for a variety of selective transformations in organic synthesis, from epoxidation of alkenes to the conversion of alcohols into fee corresponding ketones <99CJC308>. Dioxirane-mediated epoxidation continues to be the method of choice for complex substrates wife acid-sensitive functionality. Thus, fee dimethyl-dioxirane (DMD)-mediated epoxidation of the silylated stilbene lactam 159 has been reported as a key step in fee synthesis of protoberberines <99JOC877>. 

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