Epoxidation enol ester

Dimethyldioxirane DMDO discovered by Murray and coworkers, is a superior choice for the epoxidation of most olefins, giving comparable or higher yields than m-CPBA-based epoxidation [21]. Proceeding rapidly under neutral and mild conditions, it is especially well suited for the synthesis of sensitive epoxides of enol esters, enol lactones [22], and enol ethers [23]. The reaction is stereospecific, gen-... 

When this reaction sequence is applied to enol esters or enol ethers, the result is a-oxygenation of the starting carbonyl compound. Enol acetates form epoxides that rearrange to a-acetoxyketones. 

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

Energy transfer quantum yields, chemiluminescence, 1223 Enhanced chemiluminescence, 1219-20, 1221 Enol esters, dioxirane asymmetric epoxidation, 1150... 

It should finally be pointed out that the mild reaction conditions typically employed in dioxirane-mediated oxidations enable the asymmetric epoxidation of enol ethers and enol esters. With the silyl ethers, work-up provides enantiomeri-cally enriched a-hydroxy ketones. As summarized in Table 10.1, quite significant enantiomeric excesses were achieved by use of catalyst 10 at loadings ranging from 30 [30] to 300 mol% [31]. Enol esters afford the intact acyloxyepoxides enantiomeric purities are, again, quite remarkable. 

Asymmetric Epoxidation of Representative Hydroxyalkenes and Enol Esters by Ketone 1... 

S. K. Taylor, Reactions of Epoxides with Ester, Ketone and Amide Enolates , Tetrahedron 2000, 56, 1149-1163. 

These epoxides can be converted to vinyl siloxycyclopropanes m high yield by treatment with base and trimethylsilyl chloride. Transformations of these interesting intermediates (see Section VII) into various products are demonstrated in equation 103. Isolation of oxaspiropentanes is not required in a route to cyclobutanones which are formed by straightforward acid workup (equation 104) . These can either be expanded to y-butyrolactones by oxidation or to an enol ester by a-formylation and acid-induced fragmentation. The latter sequence has been utilized in a synthesis of acorenone... 

Scheme 2 summarizes the n systems with electron-donating substituents. These include 1,2-bis-trimethylsilyloxycycloaIkenes [10] 1 benzo-p-dioxin [10] 2 tetra-benzyl-O-glycal [10] 3 oxazoline [11] 4 silyl enol ethers [12] 5 enol phosphates [12b], [13] 6 enol esters [12], [14] 7 butyrolactones [14] 8 phthalide [12] 9, enol lactones [12] 10 benzofurans [15] 11 and hydroquinones [16] 12. The labile epoxides were obtained in essentially quantitative yields and spectrally characterized. 

The ability of non-C2 symmetric ketones to promote a highly enantioselective dioxirane-mediated epoxidation was first effectively demonstrated by Shi in 1996 [114]. The fructose-derived ketone 44 was discovered to be particularly effective for the epoxidation of frans-olefins (Scheme 17 ). frans-Stilbene, for instance, was epoxidized in 95% ee using stoichiometric amounts of ketone 44, and even more impressive was the epoxidation of dialkyl-substituted substrates. This method was rendered catalytic (30 mol %) upon the discovery of a dramatic pH effect, whereby higher pH led to improved substrate conversion [115]. Higher pH was proposed to suppress decomposition pathways for ketone 44 while simultaneously increasing the nucleophilicity of Oxone. Shi s ketone system has recently been applied to the AE of enol esters and silyl enol ethers to provide access to enantio-enriched enol ester epoxides and a-hydroxy ketones [116]. Another recent improvement of Shi s fructose-derived epoxidation reaction is the development of inexpensive synthetic routes to access both enantiomers of this very promising ketone catalyst [117]. 

Reactions of epoxides with ester, ketone and amide enolates 00T1149. b. Synthesis of Oxiranes. 

The first few steps in an alternative scheme are analogous to those used to introduce a hydroxyl group at Cn in progestins in Chapter 6 (Scheme 6.18). Treatment of the 11 -oxopregnane (5-1) with acetic anhydride in the presence of mineral acids converts both ketones to their respective enol acetates the hydroxyl at C3 is also acetylated in the process (5-2) (Scheme 7.5). Oxidation of that intermediate converts the side chain unsaturation to an epoxide the enol ester in... 

Enantioselective isomerization. Epoxides of enol esters provide chiral oi-acyloxy ketones and chiral starting materials. 

Nucleophilic Attack at Halogen. Further studies have been reported of the reactions of diols with the triphenylphosphine-carbon tetrachloride reagent. It has now been applied to 1,2-diols (in the presence of potassium carbonate) to form epoxides and to the trans-6 o (84), the nature of the product depending on the relative amounts of phosphine and diol present. The major product of reactions involving equimolar quantities of phosphine and diol is (85). The cyclodehydration product (86) is formed in only poor yield. In the presence of carboxylic acids, the triphenylphosphine-carbon tetrachloride system causes ring-opening of epoxides with the formation of c -enol esters, the reaction presumably proceeding via nucleophilic attack by the oxirane at an acyloxyphos-phonium intermediate. ... 

Dianions of this type react with ketones, epoxides,and esters " as well as a wide variety of other electrophiles. As an example, the dilithio anion of 2-methylpropionic acid was condensed with the epoxide moiety in 229 to form an hydroxy acid, which cyclized to form the lactone ring in 230. Since most of the enolates of acid derivatives contain a leaving group, the alkoxide resulting from reaction with an epoxide often displaces that leaving group to give the lactone. 

The related imidophosphorane wherein Z = PhCH2N, and its acyclic analogue PhCH2N=P(NMe2)3, are very efficient catalysts for the protective acylation of alcohols in the presence of enol esters [96]. Acid-labile groups (such as acetal and epoxide) survive and groups such as TBS and disulfide [which undergo... 

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