Epoxidation silyl enol ether

A more synthetically reliable version of this reaction involves epoxidation of silyl enol ethers. Epoxidation of the silyl enol ethers followed by aqueous workup gives a-hydroxyketones and a-hydroxyaldehydes.144... 

The area of reactions of phosphate derivatives has been dominated by highly stereoselective reactions in which the latter were used as chiral catalysts or achiral reagents. Among this group of reactions, it is worthy to note several asymmetric reactions ring opening of w 50-aziridinium and episulfonium ions, addition of alcohols to imines, 1,3-dipolar addition of aldehydes, amino esters and dipolarophiles, protonation of silyl enol ethers, epoxidation of a,p-unsaturated aldehydes, aza-ene-type reactions as well as asymmetric versions of named reactions Mannich, Friedel-Crafts, Kabachnik-Fields, aza-Darzens and aza-Henry. 

Silyl enol ethers are a class of electron-rich, nonaromatic compounds that easily form reactive radical cations on one electron oxidation. The silyl enol ether functional group is closely related to the carbonyl function and consequently, syntheses of silyl enol ethers generally make use of enolates. In addition, silyl enol ethers can be described as masked enols or enolates since their reactions often yield ketones. A number of oxidation reactions of silyl enol ethers making use of oxygen or oxygen-containing reagents such as peroxides, peracids (known as Rubottom oxidation), dioxirane, osmium tetraoxide, or triphenyl phosphite ozonide have been described in the literature. In all cases either a-hydroxy-ketones or the silyl enol ether epoxides are formed. 

The first asymmetric Mn(salen)-catalyzed epoxidation of silyl enol ethers was carried out by Reddy and Thornton in 1992. Results from the epoxidation of various silyl enol ethers gave the corresponding keto-alcohols in up to 62% ee Subsequently, Adam and Katsuki " independently optimized the protocol for these substrates yielding products in excellent enantioselectivity. 

The silyl enol ethers of ketones are also oxidized to a-hydroxy ketones by m-chloroperoxybenzoic acid. If the reaction workup includes acylation, a-acyloxy ketones are obtained.250 These reactions proceed by initial epoxidation of the silyl enol ether, which then undergoes ring opening. Subsequent transfer of either the O-acyl or O- l MS substituent occurs, depending on the reaction conditions. 

Reactions of 1 with epoxides involve some cycloaddition products, and thus will be treated here. Such reactions are quite complicated and have been studied in some depth.84,92 With cyclohexene oxide, 1 yields the disilaoxirane 48, cyclohexene, and the silyl enol ether 56 (Eq. 29). With ( )- and (Z)-stilbene oxides (Eq. 30) the products include 48, ( > and (Z)-stilbenes, the E- and Z-isomers of silyl enol ether 57, and only one (trans) stereoisomer of the five-membered ring compound 58. The products have been rationalized in terms of the mechanism detailed in Scheme 14, involving a ring-opened zwitterionic intermediate, allowing for carbon-carbon bond rotation and the observed stereochemistry. 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

Silyl enol ether 139 has also been transformed into D-allose, as shown in Scheme 5. The same methods can be applied to the enantiomeric enol ether derived from camphanate 38, and this allows one to prepare L-allose and its derivatives. Oxidation of 139 with MCPBA in THF (20 °C) led to the product of epoxide acidolysis 147 (69 %) which yielded 148 on heating to 200 °C for 15 min. Addition of 1.1 equiv. of MCPBA converted 148 into lactone 149 which in the presence of MeOH and K2CO3 (20 °C), gave selectively diester 150. Reactions 147... 

Other methods for a-hydroxy ketone synthesis are addition of O2 to an enolate followed by reduction of the a-hydroperoxy ketone using triethyl phosphite 9 the molybdenum peroxide-pyridine-HMPA oxidation of enolates 10 photooxygenation of enol ethers followed by triphenylphosphine reduction 11 the epoxidation of trimethyl silyl enol ethers by peracid 1 - the oxidation of trimethylsilyl enol ethers by osmium tetroxide in N-methylmorpholine N-... 

Silyl enol ethers with stereogenic silicon atoms bearing chiral alkoxy groups on silicon, as in 193, induce modest stereoselectivity in peracid epoxidation of the enol double bond306. Aryl n participation has been observed in the epoxidation of the bicylooctene 194307. 

Selective opening of allylic epoxides (9, 329-330). The reaction of the trimethyl-silyl enol ether (I) of a, /Tepoxycyclohexanone with lithium dimethylcuprate (or di-n-butylcuprate) in THF proceeds as expected to give 2.25,26 However when the reaction is conducted in ether, 2 and 3 are formed in about equal amounts.26... 

Cavallo et al. from (+)-dihydrocarvone and evaluated in the asymmetric epoxida-tion of several silyl enol ethers [32]. Enantiomeric excess up to 74% was achieved in the epoxidation of the TBDMS trans-enol ether of desoxybenzoin with the fluoro ketone 19d (30 mol% of the ketone catalysts). In earlier work Solladie-Cavallo et al. had shown that the fluoro ketones 19a and 19e can be used to epoxidize trans-stilbene with up to 90% ee (30 mol% ketone catalyst) [33], Asymmetric epoxidation of trans-methyl 4-para-methoxycinnamate using ketone 19e as catalyst is discussed in Section 10.2. 

Step 2a Regio- and stereoselective epoxidation of the more nucleophilic silyl enol ether (double bond). Although it seems at first counterintuitive, the epoxidation occurs from the (3-face (build a molecular model). 

Oxygenation of silyl enol ethers. Oxygenation of a silyl enol ether under the conditions cited above results in a silyloxy epoxide, which rearranges spontaneously to an a-silyloxy ketone. The preferred Ni catalyst for this epoxidation is bis(3-methyl-2,4-pentanedionato)nickel(II), Ni(mac)2. The a-silyloxy ketone is converted... 

The first enantioselective polyene tetracydization starting with a chiral epoxide was reported by Corey et al. in 1997 [8a]. The silylated enol ether 3 (Scheme 1) was converted into the tetracycle 4 by treatment with the Lewis acid MeAlCl2 at -90 °C. The synthetic route is modeled on the biosynthesis of lanosterol from (3S)-squalene 2,3-epoxide and has also been applied to the biomimetic synthesis of tetracyclic polyprenoids from sediment bacteria [8b]. 

Heathcock has reported an anomalous case of ozonolysis of a silyl enol ether. Usually these substrates undergo facile oxidative cleavage in the same manner as alkoies. However, in this instance the a-silyloxy ketone (61) was obtained in quantitative yield. The inteimediacy of a silyloxy epoxide was suggested. A more recent leport has indicated that a similar process is competitive with the simple cleavage reaction, (63a) versus (63b), in the ozonolysis of the steroidal enol ether (62). 

In a maimer exactly analogous to the a-hydroxylation of ketone silyl enol ethers (Sections 2.3.2.1.3.i and 2.3.2.2.3.i) the corresponding ester silyl ketene acetals may be epoxidized by poacid and subsequently cleaved with fluoride to reveal the a-hydroxy ester.Yiel are good if hexanes are employed as solvent, while competing hydrolysis hampers the process in other media. The equivalent lactone hydroxylations are, however, not possible since hydrolysis is the dominant process even in hexane. This solvent limitation may prove restrictive to the widespread use of this technique. 

Most frequently the reactions are performed by treating the crude silyl enol ether with MCPBA at 0-25 C in dichloromethane. Solvent effects have been observed. Thus treatment of enol ether (53) with MCPBA in ether resulted in isolation of the benzoate (54). This was considered to arise as a result of the increased nucleophilicity of the residual carboxylic acid in ether over that in dichloromethane. Isolation of the silyloxy epoxide by an analogous ethereal oxidation suggests perhaps that the 1,4-silyl migration is intrinsically less facile in this solvent. Generally however the process is efficient and simple substrates are readily oxygenated (Scheme 11). 

Synthetic application includes Paquette s recent s lication in work directed toward the total synthesis of sterpuric acid. Exposure of enol ether (55) to peracid provided a single diastereomer of the silyloxy compound (56) in good yield. It was from this substrate (55) that the first stable trimethylsilyloxy epoxide was obtained (57) and examined by X-ray crystallography. Similarly stereoselective oxygenation of p-keto ester (49) via the corresponding silyl enol ether provided (50), also in 76% yield. Lastly efficient and highly stereoselective a-hydroxylation by this method was employed during studies towards the synthesis of helenanolides (58 to 59). ... 

Asymmetric epoxidation of silyl enol ethers mediated by a derivative of 3 (possessing a 3-nitro-phenyl group instead of a pentafluorophenyl group) gave a-hydroxy ketones with up to 62% ee. These reactions were shown to proceed through unstable a-siloxy epoxides5. 

Hegedus and co-workers isolated a cyclobutane-fused epoxide intermediate in the Rubottom oxidation of silyl enol ether 17 (Scheme 9) <1998JOC4691>. 

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