Mono enol ethers

Moeller has carried out an extensive series of studies of the electrochemical oxidation of electron-rich w-alkenes. One olefinic component is an enol ether, which is converted into an electrophilic center upon oxidation this center then attacks the other site intramolecu-larly. The anodic oxidation of the bis-enol ethers 21 in methanol25 exemplifies the course of such reactions (Scheme 4). The products are w-acetals (22), formed in 50-70% yield in many cases. The cyclization can be used to produce quaternary25 and angularly fused26 bicyclic and tricyclic structures (equation 11). In its original form, this work involved oxidation of a mono-enol ether bearing a nearby styrene-type double bond27. 

Mono-enol ethers of -diketones (26) are formally alkoxy substituted enones, and by reductive coupling followed by hydrolysis they yield conjugated bis-enones [Eq. (8)]. This is the more stable product, independent of whether the initial coupling product is a pinacol, a bis-ketone, or mixed coupling product. Reduction of the substrates (26a-b) in ethanol/water (1 1) (Me4NCl) gave the corresponding bis-enones in 20-40% yield [101]. 

Mono-enol ethers of j3-dicarbonyl compounds have been used more frequently than mono-acetaJs, and they are more stable. From simple /3-diketones they can be prepared under esterification conditions [244a, 245], and frequently with isobutanol [246, 247, 248, 249, 250]. However, methyl enol ethers can also be prepared using diazomethane [251, 252]. Usually the less-hindered ketone group is converted into its enol ether [249, 250]. In /3-keto aldehydes the aldehyde can be converted by O-alkylation of the enolate salt with a bulky alkylating a nt such as isopropyl bromide [247, 253]. 

Cyclopentane-l,2-dione can be transformed in good yield into its isobutyl mono-enol ether in the same way as the 1,3 dione reaction of the free ketone group with Grignard reagents followed by dehydration of the intermediate carbinol constitutes a general synthesis of 2-alkyl-cyclopentenones... 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

Regiospecific mono-C-alkylation (60-90%) of trimethylsilyl enol ethers is promoted by benzyltriethylammonium fluoride [34, 35]. A similar alkylation of tin(IV) enolates is aided by stoichiometric amount of tetra-n-butylammonium bromide and has been utilized in the synthesis of y-iminoketones [36]. Carbanions from weakly acidic carbon acids can be generated by the reaction of their trimethylsilyl derivatives with tetra-n-butylammonium triphenyldifluorosilicate [37] (see also Section 6.3). Such carbanions react readily with haloalkanes. Tautomeric ketones in which the enol form has a high degree of stabilization are O-alkylated to form the enol ether, e.g. methylation of anthrone produces 9-methoxyanthracene [26],... 

Hydration of allene and mono- and disubstituted allenes leads to ketones through the rearrangement of the intermediate enols.29 Further details of the mechanism are not known, but protonation of the terminal carbon in monosubstituted allenes is probable. Although the formation of isomeric ketones may be expected, only ketones possessing the keto function on the central carbon of the allene bond system were found to form.30 When alcohols add to allenes, enol ethers of the corresponding ketones are usually the products. They may further react to form acetals. Hg2+ salts may be used as catalysts.31... 

C. Fayet and J. Gelas, Reaction of mono- and oligo-saccharides with keto or ethylenic enol ethers as a route to functionalized acetals and monomers for polymerization, Carbohydr. Res. 259 177 (1993). 

Mixtures of 4-(difluoroiodo)toluene and anhydrous phosphoric acid form a nonisolated hypervalent iodine species, probably PhI(0H)(0P03H2), which reacts with silyl enol ethers producing tris-ketol phosphates. Interestingly, mono- or bis-ketol phosphates could not be obtained using the appropriate stoichiometry. 

Simple mono- or di-substituted enol ethers may be oxidized to esters and lactones (Table 8, entries 1 and 2). However, fully substituted enol ethers undergo oxidative cleavage, since the proposed mechanism for oxidation to an ester involves a hydride shift which can no longer take place. 

Clerici A, Pastori N, Porta O (2001) Mild acetalisation of mono and dicarbonyl compounds catalysed by titanium tetrachloride. Eacile synthesis of (3-keto enol ethers. Tetrahedron 57 217-225... 

Silyl enol ethers are converted to a-thioalkyl and a-thioaryl ketones via a sulfe-nylation method, driven by aromatization of an added quinone mono-0,5 -acetal in the presence of Me3SiOTf. ... 

Aldehydes may be prepared from the lower homolog or a ketone or ester by reaction with the anion of formaldehyde mono- or dithioacetal. The j6-hydroxythioacetal may be reduced with elimination of a hydroxyl group and phenylthiolate. The resulting enol ether or thioenol ether can be transformed into an aldehyde on acid hydrolysis or reaction with mercuric chloride [82],... 

Sammes and cowoikers devised a promising solution to the synthesis of substituted P-silyl sulfones, which has been exploited in a new approach to the antibiotic bicyclomycin (Scheme 44). In their approach the P-silyl sulfone (125) was prepared by conjugate addition of the lithium enolate of the mono-imino ether derivative (123) of a dioxopiperazine to the unsaturated P-silyl sulfone (124). After oxidative cyclization to the bicyclic system (126), the latent alkene functionality was unleashed in 89% yield on treatment with TBAF in THF at room temperature to give the basic skeleton of bicyclomycin. 

An interesting variant of the Nenitzescu indole synthesis, involving the Lewis acid-directed coupling of enol ethers with benzoquinone mono- and b/s-imides, was developed by T.A. Engler et al. for the synthesis of substituted - and -tetrahydrocarbolines. ... 

The reaction has been investigated with MeOH, - z-PrOH, - t-BuOH, " phenols, " cyclic allylic alcohols, - homoallylic alcohols, 3,4-hydroxybenzoate, and mono Z-butyldimethyl-silyl protected diols. A subsequent Homer-Wadsworth-Emmons olefination with a range of aldehydes affords the corresponding enol ethers. ... 

The occurrence of two competing pathways was also observed in the reaction of some enol silyl ethers with diphenyliodonium fluoride (19), which afforded the mono- or the di-phenylated products in moderate to good yields. This C-phenylation reaction is likely to occur by a ligand coupling process. However, with some hindered silyl enol ethers, for example (20), diketone dimers (21) were also isolated, indicative of a free-radical component in the overall mechanistic picture. ... 

Methoxy- and 2-acetoxy-furans are available from 2,5-dimethoxy- and 2,5-diacetoxy-2,5-dihydro-furans (18.1.1.4) via acid-catalysed elimination. They undergo Diels-Alder cycloadditions the adducts can be further transformed into benzenoid compounds by acid-catalysed opening. 3,4-Dihydroxyfuran is undetectable in tautomeric equilibria between mono-enol and dicarbonyl forms the dimethyl ether behaves as a normal furan, undergoing easy a-electrophilic substitution, mono- or dilithiation at the a-position(s), and Diels-Alder cycloadditions. 2,5-Bis(trimethylsilyloxy)furan is synthesised from succinic anhydride it too undergoes Diels-Alder additions readily. Both furan-2- and -3-thiols can be obtained by reaction of lithiated furans with sulfur in each case the predominant tautomer is the thiol form. ... 

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