Silyl enol ethers cleavage

Schafer reported that the electrochemical oxidation of silyl enol ethers results in the homo-coupling products. 1,4-diketones (Scheme 25) [59], A mechanism involving the dimerization of initially formed cation radical species seems to be reasonable. Another possible mechanism involves the decomposition of the cation radical by Si-O bond cleavage to give the radical species which dimerizes to form the 1,4-diketone. In the case of the anodic oxidation of allylsilanes and benzylsilanes, the radical intermediate is immediately oxidized to give the cationic species, because oxidation potentials of allyl radicals and benzyl radicals are relatively low. But in the case of a-oxoalkyl radicals, the oxidation to the cationic species seems to be retarded. Presumably, the oxidation potential of such radicals becomes more positive because of the electron-withdrawing effect of the carbonyl group. Therefore, the dimerization seems to take place preferentially. 

Bromide 280 (derived by bromination of silyl enol ether 270) undergoes both zinc- and cerium-mediated cleavage under mild and essentially neutral conditions, and was used to prepare the nucleoside-containing C-glycoside 282 (Scheme 73) [ 112,113], The aldehyde 281 used in this transformation was exceptionally sensitive to basic conditions which completely precluded use of a conventional enolate obtained by deprotonation of ketone 265 (Sect. 4.3.1). 

The abstraction of a proton a to a carbonyl group is not the only method for generating enolates and these alternative methods also offer possibilities for regio- and stereoselectivity. Thus, cleavage of silyl enol ethers (e.g., 1 and 3)9, 12 17 and enol acetates (e.g., 5)18 has been used for the generation of specific enolates. The conditions for these cleavages have to be chosen so that there is no equilibration of the lithium enolates formed. 

The preparation of silyl enol ethers and enol acetates may afford mixtures of isomers, however, these can be separated prior to cleavage. Usually the preparation of silyl enol ethers or enol acetates proceeds via one of the base-catalyzed deprotonations described previously and conditions can be applied which favor the formation of one isomer (vide supra). Thus, regio- and stereoselectivity can be achieved. An extensive review of the synthetic uses, including the preparation and reactions, of silyl enol ethers is available32. 

Methyl y-oxocarboxytates.2 Silyl enol ethers react with methyl diazoacelate in the presence of a copper salt to form siloxy-substituted cyclopropancs (1) in useful yields. Cleavage of the siloxy group with fluoride ion (4, 477 478) affords y-oxo esters (2) in good yields. 

An alternative approach to the synthesis of isocoumarins which probably proceeds through the intermediacy of 2-carboxybenzyl ketones is based on the oxidative cleavage of indan-1-ones (76JCS(P1)1438). Although ozonolysis of the silyl enol ether (505) leads to the 2-hydroxy-2-methylindan-l-one (506), periodate oxidation of which gives the isocoumarin, a more convenient and direct route involves ozonolysis of the enol trifluoroacetate (Scheme 182). This synthesis is especially attractive for the preparation of isotopically labelled isocoumarins, since the precursors of the indanones, arylpropanoic acids or acrylophenones, are readily available bearing labels at specific sites. 

A much more general synthesis of these silyl enol ethers, however, is based on the reductive cleavage of the carbon-sulphur bond of the silyl enol ether of a thiolester using sodium metal and chlorotrimethylsilane, once again in a silyl acyloin reaction (Scheme 22)97,98. 

Chromium-containing silicalite-2, CrS-2, has been synthesized and shown to catalyze similar reactions using TBHP as an oxidant [109]. Notably, TBHP has been reported to be an ineffective oxidant in TS-1 catalyzed oxidations [26]. However, it has been claimed that aTS-1-TBHP combination exhibits activity in the oxidative cleavage of the C=C double bond of silyl enol ethers to produce dicarboxylic acids [110]. 

Cleavage of silyl enol ethers. The double bond of silyl enol ethers is cleaved to curbonyl compounds by reaction with r-butyl hydroperoxide in the presence of cntuly tic amounts of Mo02(acac)2. ... 

The photochemical addition of cyclic 1,3-diones such as dimedone, 1,3-cylohexandione 62, or their respective silyl enol ethers leads to the formation of two fused furanylfullerenes, (1) achiral 63 and (2) chiral 64 [244], The latter having an unusual bis-[6,5] closed structure. In the initial step of this reaction, [2 + 2] photocycloaddition across a [6,6] bond to form cyclobutanols or the corresponding TMS ethers is involved (Scheme 26). Oxidation with 02 yields in the formation of the radical 65a. Cleavage to 66a followed by cyclization gives furanyl radical 67a. H abstraction by 102 or a peroxy radical finally leads to product 63. In competition, formation of fullerene triplets by absorption of a... 

Annelation-ring cleavage.1 A bifunctional reagent with an acetal and an allylsi-lane group can be used for annulation of silyl enol ethers to six- and seven-membered carbocycles (equation I).2 The reaction involves conjugate addition to give an adduct that undergoes intramolecular cyclization. 

In contrast, the related silyl enol ethers are available by mild selective transformations from carbonyl compounds or other precursors 55). Their stability and that of products derived from these alkenes can easily be regulated by choosing suitable substituents at silicon. Selective cleavage of a Si—O-bond is possible with fluoride reagents under very mild conditions, and this is why cyclopropane ring opening can now be performed with high chemoselectivity. 

Table 2. Synthesis of methyl 2-siloxycyclopropanecarboxylates 97 from methyl diazoacetate and silyl enol ethers 96 according to Eq. 28 and ring cleavage to y-oxoesters 98... 

If the olefin is chiral (entries 23-25) high diastereoselectivity has been observed, when the center of asymmetry is at C-3 of cyclic silyl enol ethers (entry 24). Cyclopropanation then occurs trans to the substituent at this carbon 57) exclusively, and due to the very mild cleavage conditions this mww-relationship is preserved in the subsequent ring opening (vide infra). This protocol has been applied to introduce a side chain during the stereoselective synthesis of a prostaglandin58> and of dicranenone A 59). 

The bottom reaction of Figure 14.26 shows an oxidative cleavage of the same menthone with the opposite regiochemistry. In a preparatory step, menthone is converted into the silyl enol ether B via its kinetic enolate (cf. Figure 10.9). The C=C double... 

The kinetic reprotonation by a series of carbonyl-based acids, of the lithium enolate obtained from 2,4-dimethyltetralone either by LDA-mediated deprotonation or by cleavage of its silyl enol ether, was studied by Eames (Scheme 71)352. The diastereoselective ratio, close to the thermodynamic value, obtained with methanol (pKa = 29 in DMSO) is probably due to equilibration. The difference observed in the presence of an additive was interpreted as the result of a fine balance between the coordinating ability, the intrinsic acidity, and probably the concentration of the enolic form of the cyclic and linear dicarbonyl acidic compounds. 

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). 

Mo02(acac)2 and r-butyl peroxide when dissolved in benzene form a reagent that can be used for the specific cleavage of silyl enol ethers. For example, the silyl ether of p-ionine is selectively deaved as indicated in equation (35), to give -(2,6,6-trimethylcyclohexyl)acrylicacid. 

Since the formation of silyl enol ethers from the corresponding ketones is subject to dther thermodynamic or kinetic control, Ais reagent can be used (as demonstrated in equation 36) to achieve useful regiospecific cleavages. 

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