Epoxides silyl, rearrangement

For the very first report of a C- to O-silyl rearrangement occurring after epoxide opening with 2-TMS-l,3-dithiane, see P. F. Jones, M. F. Lappert, A. C. Szary, Journal of the Chemical Society, Perkin Transactions l 1973, 2272... 

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... 

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. 

When the present efficient epoxidation catalyzed by nickel(II) complex was applied to the oxidation of enolates, a-siloxy carbonyl compounds were obtained via possible silyl rearrangement of siloxy epoxides. And a-hydroxy carbonyl compounds were obatined in good yields by successive desilylation with potassium fluoride (Scheme 7). 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

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]. 

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. 

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

Epoxidations of chiral allenylsilanes are also highly stereoselective, especially if the silyl group is spatially demanding (Eq. 9.54) [60]. A bis-epoxide intermediate is formed which rearranges to an a,/8-unsaturated a -hydroxy ketone. Such products are of interest as branched carbohydrate analogues. 

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. 

Stereopure epoxide 1 was prepared and treated with 3.6 equivalents of t-butyllithium in THF/HMPA at -78°C. The intention was that formation of the anion at the benzylic carbon would lead to a 4-exo-epoxide ring opening reaction a subsequent [l,2]-silyl shift (Brook rearrangement) would generate the oxetane 2 with stereocontrol at all three stereocentres. Anion formation proceeded smoothly at -78°C, then 1 ml of 1 M hydrochloric acid was added and the product isolated. Obtained pure in 40% yield, this was shown to be the aldehyde 3. No oxetane 2 was obtained. 

The enol ether double bond is epoxidized by the peracid. Relief of the epoxide ring strain drives the rearrangement with migration of the silyl group to give the silylated a-hydroxy ketone product. 

Harada, T. Mukaiyama, T. Trityl antimonate-catalyzed sequential reactions of epoxides with silylated nucleophiles. Rearrangement of epoxides and C-C or C-O bond forming nucleophilic reaction onto the intermediate carbonyl compounds. Bull. Chem. Soc. Jpn. 1993, 66, 882-891. 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Smith et al. have developed a very elegant route to complex polyol structures by sequential dithiane-epoxide coupling reactions (Scheme 7) [16]. Following the work of Tietze [17], 2-silyl-1,3-dithianes 42 are deprotonated with /BuLi in ether and converted into the stable lithium alk-oxides 43 with enantiomerically pure epoxides. A fast 1,4-Brook rearrangement occurs only after the addition of 0.3 equivalents of hexamethyl-phosphoramide (HMPA) or 1,3-dimethylhexahy-dro-2-pyrimidone (DMPU) to the reaction mixture. A new lithiated dithiane 44 that can undergo... 

A highly useful twofold reaction of silyl dithioacetals with epoxides was described by Tietze and coworkers (Scheme 2.107) [249]. Treatment of 2.2equiv. of enan-tiopure epoxides 2-463 with lithiated silyldithiane 2-458b in the presence of a crown ether led to 2-467 after aqueous work-up. It can be assumed that by attack of the lithium compound 2-462 at the sterically less-hindered side of the epoxide 2-463, the alkoxide 2-464 is formed which in a subsequent Brook rearrangement produces the lithium dithioacetal 2-465. This reacts again with an epoxide to give 2-466 and furthermore 2-467. Treatment with NaF then leads to the diol 2-468 which can be converted into the dihydroxy ketones 2-469 and the corresponding 1,3,5-triols, respectively. 

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