Enones, direct epoxidation

Similar to Jones reagent, Collins reagent can produce a hydroxy directed epoxidation of allylic alcohols. This side-reaction only occurs in a limited number of allylic alcohols, most of them being oxidized uneventfully to the corresponding enones.117... 

The expected enone is obtained in 40% yield. A 15% yield of the product, resulting from hydroxy-directed epoxidation followed by oxidation to ketone, is obtained. A third product, obtained in 30% yield, can be explained by the equilibration of the initially formed allylic chromate ester with an isomeric chromate ester that directs the epoxidation of an alkene, giving an epoxy alcohol that is further oxidized to an... 

Isolated carbon-carbon multiple bonds are not normally attacked by Jones reagent, but some doublebond isomerization may occur during the preparation of a, -unsaturated aldehydes. Hydroxy-directed epoxidation (presumably via chromate ester formation, followed by oxygen transfer to the double bond) has also been observed in steroidal substrates for axial alcohols (equation 1). Equatorial alcohols undergo oxidation to give the expected enone. 

This transformation has found extensive use in converting cyclopentenone and cyclohexenone ring systems to the rearranged allylic alcohols during the course of the total syntheses of natural products. In the preparation of ( )-quadrone (Scheme 12), the tricyclic enone was epoxidized and the resulting a,P-epoxy ketone treated with hydrazine to afford the allylic alcohol. The cyclopropane-directed epoxidation shown in Scheme 13 gives an allylic alcohol that is taken on to (-)- and (+)-carenones. In the total syn-... 

If the diene is unsymmetrical, particularly if the monoepoxide of the less substituted and therefore less nucleophilic alkene is wanted, alternative methods are required. The enone 269 provides both epoxides 270 and 267. The sulfur ylid route converts the enone directly to one epoxide while base-catalysed epoxidation followed by a Wittig reaction provides the other. 

Similarly, enone 38 has been shown to undergo ketone-directed epoxidation when treated with MCPBA to give exclusively the syn epoxyketone 40. As for the mechanism, hydrogen bonding effects were discounted on the basis of solvent insensitivity. Intramolecular attack by some oxidized form of the ketone moiety could be operative, although labelling studies have ruled out a dioxitane intermediate as... 

MBH adducts have been transformed into acyloxiranes 453 by using iodo-sobenzene activated by a catalytic amount of KBr in water at room temperature. lodosobenzene has been utilized here for two-fold oxidation of a secondary alcohol of a MBH adduct followed by subsequent epoxidation of the generated enone in a one-pot synthesis of an acyloxirane (Scheme 3.199). Complementarily to the syn diasteroselectivity obtained in the direct epoxidation of MBH adducts, mono-TBS protected allylic diols 454 derived from... 

The epoxidation of electron-deficient alkenes, particularly a,P-unsaturated carbonyl compounds, continues to generate much activity in the literature, and this has been the subject of a recent concise review <00CC1215>. Additional current contributions in this area include a novel epoxidation of enones via direct oxygen atom transfer from hypervalent oxido-).3-iodanes (38), a process which proceeds in fair to good yields and with complete retention of... 

Direct phase-transfer catalysed epoxidation of electron-deficient alkenes, such as chalcones, cycloalk-2-enones and benzoquinones with hydrogen peroxide or r-butyl peroxide under basic conditions (Section 10.7) has been extended by the use of quininium and quinidinium catalysts to produce optically active oxiranes [1 — 16] the alkaloid bases are less efficient than their salts as catalysts [e.g. 8]. In addition to N-benzylquininium chloride, the binaphthyl ephedrinium salt (16 in Scheme 12.5) and the bis-cinchonidinium system (Scheme 12.12) have been used [12, 17]. Generally, the more rigid quininium systems are more effective than the ephedrinium salts. 

The mechanism by which the hydroperoxide intermediate, (42) (Scheme 29) is converted into the products of Scheme 28 is not clear. The follow-up reaction of (42) may be diverted by reaction with an enone that undergoes epoxidation in 85 to 90% yield. Scheme 29, [121]. The epoxidation reaction does not take place directly from O2 and 02 but requires the formation of an intermediate of type (42) derived either from the enone or from an external carbon acid as in Scheme 29. Yields are considerably improved using an external carbon acid since the Michael addition between the enone and its anion otherwise competes with the epoxidation. For... 

Many of the enone substrates used in polyamino acid-catalysed epoxidation reactions can be made via a simple aldol condensation, which leads directly to the desired enone after in situ dehydration. Enones that cannot be synthesised by the above route may often be synthesised using standard Wittig chemistry, (Scheme 6). The above methods of substrate synthesis provide compounds with a variety of groups R and enabling the incorporation of both aliphatic and aromatic moieties into the enone structure. 

The epoxidation of enones using chiral phase transfer catalysis (PTC) is an emerging technology that does not use transition metal catalysts. Lygo and To described the use of anthracenylmethyl derivatives of a cinchona alkaloid that are capable of catalyzing the epoxidation of enones with remarkable levels of asymmetric control and a one pot method for oxidation of the aUyl alcohol directly into... 

The remaining chapters deal with a variety of catalysts for effecting oxidation reactions. Chapter 5 describes three simple protocols for the controlled oxidation of primary or secondary alcohols. The importance of stereocontrolled epoxidation and hydroxylation reactions is reflected by the fact that Chapter 6, directed at this field, is one of the most extensive sections of the book. An interesting example of an enantioselective Baeyer-Villiger reaction is featured in Chapter 7, together with an industrially important ketone to enone conversion. Oxidative carbon-carbon... 

Sometimes, chromate esters from secondary a]]vi-transposition rather than direct oxidation, the rLI" ° l0ls Suffer chromate ester can either produce epoxidation of the iv transPosed oxidation yielding a transposed enone.84 a ene or suffer... 

Why does the stabilized ylid prefer to react with the double bond In order to understand this, let s consider first the reaction of a simple, unstabilized ylid with an unsaturated ketone. The enone 1 has two electrophilic sites, but from Chapters 10 and 23, in which we discussed the regioselectivity of j attack of nucleophiles on Michael acceptors like this, you would expect that direct 1,2-attack on the i ketone is the faster reaction. This step is irreversible, and subsequent displacement of the sulfide i leaving group by the alkoxide produces an epoxide. It s unimportant whether a cyclopropane prod- uct would have been more stable ihe epoxide forms faster and is therefore the kinetic product. 

The overall sequence could be realized by 1,4-addition of a nucleophile to the enone and subsequent quenching at the a-position followed by B-elimination of the initial nucleophilic component. Such multistep processes will not be discussed here. However direct hydroxylation methods are scarce. Mo-riarty has reported that a,3-unsaturated ketones are oxidized by phenyliodosyldiacetate at the a-site in preference to the a -position, e.g. (138) to (139), although no yield has bWn indicated. There is no available mechanistic rationale, although the intermediacy of the a,B-epoxide is precluded. 

Previous work by Jeger and his coworkers has studied the photoreactivity of y.5-epoxy enones. More recent work by Ishii et aJ has examined the photochemical reactivity of the related nitriles (145) and (146). The direct irradiation of (145) brings about isomerization by ring opening of the cyclopropane to afford (147) as the major product. This is accompanied by the cyclopropenyl nitrile (148) presumably formed via a carbene intermediate. Triplet sensitized irradiation of (145) only brings about trans-cis isomerization. The epoxide (149) is also photoreactive and direct irradiation affords the products (150) - (156) either by the intermediacy of an ylide (157) or a carbene (156). ... 

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