Epoxidation electron-deficient

Electron deficient carbon-carbon double bonds are resistant to attack by the electrophilic reagents of Section 5.05.4.2.2(t), and are usually converted to oxiranes by nucleophilic oxidants. The most widely used of these is the hydroperoxide ion (Scheme 79). Since epoxidation by hydroperoxide ion proceeds through an intermediate ct-carbonyl anion, the reaction of acyclic alkenes is not necessarily stereospecific (Scheme 80) (unlike the case of epoxidation with electrophilic agents (Section 5.05.4.2.2(f)) the stereochemical aspects of this and other epoxidations are reviewed at length in (B-73MI50500)). 

A more efficient agent than peroxy compounds for the epoxidation of fluoro-olefins with nonfluonnated double bond is the hypofluorous acid-acetomtrile complex [22] Perfluoroalkylethenes react with this agent at room temperature within 2-3 h with moderate yields (equation 13), whereas olefins with strongly electron-deficient double bond or electron-poor, sterically hindered olefins, for example l,2-bis(perfluorobutyl)ethene and perfluoro-(l-alkylethyl)ethenes, are practically inert [22] Epoxidation of a mixture of 3 perfluoroalkyl-1-propenes at 0 C IS finished after 10 mm in 80% yield [22] The trifluorovinyl group in partially fluorinated dienes is not affected by this agent [22] (equation 13)... 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

With electron-deficient aromatic substrates (Entries 4 and 5), high yields and selectivities were observed, but enantioselectivities were variable and solvent-de-pendent (compare Entry 6 with 7 and see Section 1.2.1.3 for further discussion). With a,P-unsaturated tosylhydrazone salts, selectivities and yields were lower. The scope of this process has been extensively mapped out, enabling the optimum disconnection for epoxidation to be chosen [10]. 

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. 

Scheme 61 Epoxidation of electron deficient olefins with silver complexes.

Metal alkyl peroxides can be used for the epoxidation of electron-deficient alkenes such as enones. The use of a combination of diethylzinc, oxygen, and A-methylephedrine gave epoxides in very high yield and generally high enantio-selectivity (Figure 11.8). " ... 

S.3 Cytochrome P450 Model Compounds Functional. Ferric-peroxo species are part of the cytochrome P450 catalytic cycle as discussed previously in Section 7.4.4. For instance, these ferric-peroxo moieties are known to act as nucleophiles attacking aldehydic carbon atoms in oxidative deformylations to produce aromatic species.An example of this work, establishing the nucleophilic nature of [(porphyrin)Fe (02)] complexes, was achieved for alkene epoxidation reactions by J. S. Valentine and co-workers. The electron-deficient compound menadione (see Figure 7.18) yielded menadione epoxide when reacted with a [(porphyrin)Fe X02)] complex. 

The epoxidation occurs at electron deficient double bonds, thus it is only the double bond adjacent to a ketone functionality that is epoxidised. This phenomenon allows scope for further elaboration of our substrates, hence several transformations have been investigated in order to diversify the nature of the products. Indeed, substrates used in the epoxidation reaction intentionally featured several functionalities which could each be modified selectively dependent upon the reaction conditions employed. Such reactions include ... 

Since the polyleucine epoxidation conditions are only favourable for highly electron-deficient unsaturated systems (i. e. ketones), use of the Baeyer-Villiger oxidation subsequent to the epoxidation reaction allows access to the optically active epoxyesters. 

Iodosylbenzene is sufficiendy reactive on its own to epoxidize electron-deficient olefins such as tetracyanoethylene (43). It is possible that coordinated monomeric iodosylbenzene is substantially more reactive than polymeric iodosylbenzene and that complexation of a monomeric form is sufficient to provide the requisite reactivity with normal olefins. 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

A high catalyst loading (typically 20-30 mol%) is usually required for the epoxidation with ketone 26 because Baeyer-Vilhger oxidation presumably decomposes the catalyst during the epoxidation. The fused ketal moiety in ketone 26 was replaced by a more electron-withdrawing oxazohdinone (32) and acetates (33) with the anticipation that these replacements would decrease the amount of decomposition via Baeyer-Villiger oxidation (Fig. 8) [71, 72]. Only 5 mol% (1 mol% in some cases) of ketone 32 was needed to get comparable reactivity and enantioselectivity with 20-30 mol% of ketone 26 [71]. Since dioxiranes are electrophilic reagents, they show low reactivity toward electron-deficient olefins, such as a, 3-unsaturated esters. Ketone 33, readily available from ketone 26, was found to be an effective catalyst towards the epoxidation of a, 3-unsaturated esters [72]. 

Next to the base-catalyzed asymmetric epoxidations of electron-deficient olefins with chiral hydroperoxides described above, a few examples of uncatalyzed epoxidations with... 

One of the early examples for organocatalysis is the asymmetric Weitz-Scheffer epoxidation of electron-deficient olefins, which can be effected either by organic chiral phase transfer catalysts (PTC) under biphasic conditions or by polyamino acids. This reaction has gained considerable attention and is of great synthetic use. 

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