A-silyloxy-epoxides

Rearrangement of epoxy silyl ethers. When treated with 1 equiv. of TiCl4, a-silyloxy epoxides rearrange to p-hydroxy carbonyl compounds. 

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... 

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). 

Enol ethers, and in particular silylated ends (see Volume 2, Chapter 2.3), react with peroxy acid reagents to give initially a silyloxy epoxide, which rearranges with silyl migration to yield an a-silyloxy ketone, as in Scheme 3. The net result is diat a ketone is converted to a protected a-hydroxy ketone, and the stereochemistry is determined by the least hindered approach of Ae peroxy acid to the enol. 

The pinacolic rearrangement of acyclic a-silyloxy epoxides presents an attractive procedure for the stereocontrolled preparation of aldol-type products under extremely mild conditions33 35. Treatment of epoxides with an appropriate Lewis acid catalyst results in a [1,2] shift with net inversion of epoxide stereochemistry to afford highly functionalized /J-hydroxy ketones. 

The products obtained from pinacolic rearrangement of a-silyloxy epoxides can be further transformed in situ by allylsilane addition to the carbonyl group. Lewis acid treatment of 2,3-epoxy-l-phenyl-l-trimethylsilyloxybutane at low temperature followed by addition of 3-trimethylsilylpropene yields 1.3-diol 31 as the only product33. 

A large proportion of Davis s work has been involved in the elucidation of the transition state employed in the transfer of the oxygen from the oxaziridine to the olefin substrate. Davis favoured the planar transition state and was at the time supported by theoretical calculations however, more recent calculations favour the spiro transition state [6]. Davis has also described the asymmetric oxidation of enolate anions by chiral oxaziridines, which led to a-hydroxyketones with enanti-oselectivities of up to 95% ee [56, 57], Silyl enol ethers have also been reported to give epoxides when treated with oxaziridines, but the instability of these compounds is too great to allow isolation [37,58,59], To date, only Davis has reported successful isolation of a-silyloxy epoxides [60],... 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

In a synthesis of (-i-)-asteltoxin, Cha applied the Suzuki-Tsuchihashi rearrangement to silyloxy epoxide 184 for the enantioselective construction of the unusual... 

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. 

A number of acyl trimethyl silanes chiral at the a- or -carbon atom have been prepared in non-racemic form. Chiral a-alkoxy and a-silyloxy acyl silanes have been generated in very high yields by oxidative rearrangement of enantiomerically pure silyl epoxides, induced by dimethyl sulphoxide and silyl triflates (Scheme 32)112. 

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 considoed 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 periugrs that the 1,4-silyl migration is intrinsically less facile in this solvent. Generally however the process is efficiem and simple substrates are readily oxygenated (Scheme 11). 

Reagents which effect epoxidation of the enol ether unsaturation effect a-hydroxylation comparable to the peracid approach. Thus a combination of molybdenum hexacarbonyl and r-butyl hydroperoxide converts the substrates to a-silyloxy derivatives. The peroxide generate in situ from benzonitrile, potassium carbonate and hydrogen peroxide can also perform the oxidation. Molybdenum-peroxy complexes, including MoOPH, could presumably also effect this transformation. Lastly, dimethyldioxirane has been used to epoxidize alkenes and it is likely that application of this useful, debris free, organic peroxide to these reactions will soon emerge. 

Danishefsky prepared the furanophane 184 and converted it to hydropyrone 185 through a directed epoxidation with DMDO. Diastereoselective addition of methyllithium was followed by an acid catalyzed isomerization to the furanoside 186. Vinylogous aldol addition of a silyloxy furan to an imine gave 189 that was easily isomerized to the azacycle 190. Another general strategy to prepare pyran derivatives is a cycloaddition/fragmentation route involving an oxabicyclo[3.2.1]octane intermediate (Scheme 24). 

The mechanism initially proposed for the Rubottom oxidation involved epoxidation of the enolsilane to afford intermediate silyloxyoxirane 4. It was suggested that this intermediate undergoes acid-mediated cleavage to afford stabilized carbocation 5, which is transformed to the a-silyloxy ketone 6 via 1,4-silicon migration. Hydrolysis of 6 by aqueous acid in a subsequent step generates the a-hydroxy ketone 7.lb 15 Attempts to provide support for this mechanism via isolation of intermediate silyloxyoxiranes derived from simple ketones proved difficult due to the lability of these compounds. However, Brook demonstrated that the related heterocyclic silyloxyoxirane 8 was isolable and was transformed to ketone 9 upon treatment with /j-TsOH. 

Further support for the mechanism described above was obtained in subsequent studies by several groups. Direct evidence for the initial epoxidation event in the Rubottom oxidation of an acyclic enolsilane was first obtained by Weinreb, who described the isolation of silyloxyoxirane 10 and demonstrated its conversion to a-silyloxy ketone 11 upon treatment with PPTS.4 The isolation of a macrocyclic bis(silyloxyoxirane) has also been reported.5... 

It is assumed that the epoxidation of the silyl enolate yields an anomeric effect-stabilized silyloxy carbocation, which transforms into a-silyloxy ketone via 1,4-silyl migration. Hydrolysis of such o -silyloxy ketone gives the a-hydroxy ketone. A general illustration of this reaction is provided here. 

A novel silyl triflate-promoted Payne rearrangement of silyloxy epoxides was reported by Jung et al When the ethyl substituted epoxy silyl ether 13 was treated with silyl triflate in the presence of a base, a mixture of four ketones, 16a-d and four aldehydes 17a-d were obtained. It has been assumed that two ketones and two aldehydes could be formed via a non-aldol process and an epoxide rearrangement, whereas the other four products through 14 and 15, a silyl triflate promoted Payne rearrangement. 

Assembling a five-component coupling product in a single operation further extended this methodology. Following alkylation of dithiane 78 with epoxide (—)79 (2.6 equivalent each) to generate the unrearranged alkoxy dithiane 80, sequential addition of HMPA and (—)-epichlorohydrin 81 (1 equivalent) furnished the bis(silyloxy dithiane) carbinols (- -)82 in 66% yield (equation 29) . ... 

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). ... 

Stork had also recognized the symmetry element present in the erythronolide A skeleton. The Stork approach is outlined in Scheme 2.18. Cyclopentadiene was converted into the optically pure (lS,2S)-(4-)-2-methyl-3-cyclopenten-l-ol (196) utilizing literature procedures. Stereoselective syn epoxidation followed by oxidation and base treatment afforded an alcohol which was silylated to give 197 in 71% overall yield. As expected, the y-silyloxy group induced the addition... 

This approach can use the inherent regioselectivity of silyl enol ether formation (chapter 3) using kinetic or thermodynamic enolisation. Hence kinetic enolisation of enones (chapter 11) occurs on the a side leading to 2-Me3SiO-butadienes such as 222. Epoxidation of this silyl enol ether gives the unstable silyloxy ketone 223 which can be desilylated by fluoride ion and hence transformed into the hydroxyketone 225 or acetoxy ketone 224. These transformations are useful because the hydroxy ketones can be unstable34 (see below). 

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