Acetals preparation from enol ethers

Enol acetates and silyl enol ethers may be prepared from enolates. This is sometimes advantageous because they are stable enolate equivalents. Enol acetates can be cleaved with 2 equiv. of methyllithium... 

Acetals of a-bromo aldehydes are obtainable from <%,/ -dibromoalkyl acetates by an analogous procedure in which these esters are prepared from enol acetates and bromine and are then converted into acetals by means of alcohols.939 A simple synthesis of <%-keto aldehydes is to treat a-brominated phenacyl phenyl ethers with alkoxides or phenoxides.940 This method is particularly useful for the preparation of aryl acetals because it avoids the side reactions that can complicate reactions between phenols and aldehydes in an acidic medium. 

A mixture of cis- and truns-1-methoxycyclododecenes was prepared in 98% yield from cyclododecanone by a modification of Claison s method of ketal formation. Amberlyst-15 is a superior catalyst for the preparation of enol ethers and acetals. 

The photochemical reactivity of P-ketoesters is different form that of P-diketones. Irradiation of a P-ketoester in the presence of an alkene produces oxetane via the ketone carbonyl instead of the desired cyclobutane ring system. Therefore, it is necessary to covalently lock the ketoesters as the enol tautomers. To this end, silyl enol ethers, 129 and 132a, and enol acetates, 130 and 132b, were prepared, but these substrates still fail to undergo the desired intramolecular [2 + 2] photocycloaddition with olefins. The only new products observed in these reactions result from the photo-Fries rearrangement of the cyclic enol acetate (130 to 131) and cis-trans isomerization of both acyclic substrates 132a/b. However, tetronates are appropriate substrates for both intermolecular and intramolecular photocycloadditions with olefins. In addition, enol acetates and silyl enol ethers of p-keto esters are known to undergo [2 + 2] photoaddition with cyclic enones (vide infra). 

Not only silyl end ethers but also enol acetates prepared from saturated ketones give a,/3-unsaturated ketones by heating with allyl methyl carbonate in the presence of Pd(II)(OAc)2 and dppe with tributyltin methoxide as a bimetallic catalyst (Scheme 12). Regioselective generation of palladium(II) enolate intermediate is simply carried out by treatment of allyl enol carbonates, which are prepared by trapping of ketone enolates with chloroformate, with Pd(II)(OAc)2 in the presence of dppe (Scheme 13). 7r-Allylpal-ladium(II) enolates thus generated provide a,/3-nnsatnrated ketones. 

Dicarbonyl Compounds.—Ozonolysis of 2-cyclopentylidenecyclopentanone provides a convenient synthesis of cyclopentane-l,2-dione on the ca. 0.4 mole scale.The by-product, cyclopentanone, is recycled via an aldol condensation to regenerate the enone. The method should be applicable to other alicyclic 1,2-diones. Various methods for the preparation of monoprotected 1,2-diones have appeared. Monoacetals of a-dicarbonyl compounds are prepared regio-specifically from enol ethers [equation (32)], following epoxidation in methanol and oxidation of the resulting acyloin acetal. 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

The cyclic enol ether 255 from the functionalized 3-alkynoI 254 was converted into the furans 256 by the reaction of allyl chloride, and 257 by elimination of MeOH[132], The alkynes 258 and 260, which have two hydroxy groups at suitable positions, are converted into the cyclic acetals 259 and 261. Carcogran and frontalin have been prepared by this reaction[124]. 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide in ether solution, the molar equivalent of lithium iodide or lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the methyllithium. Certain of the ethereal solutions of methyl 1ithium currently marketed by several suppliers including Alfa Products, Morton/Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from methyl bromide and contain a full molar equivalent of lithium bromide. In several applications such as the use of methyllithium to prepare lithium dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates that the stereochemistry observed during addition of methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution. For these reasons it is often desirable to have ethereal solutions... 

The dimethyl acetal (94) is readily prepared from the 22-aldehyde (93) by direct reaction with methanol in the presence of hydrogen chloride. Ena-mines (95) are formed without a catalyst even with the poorly reactive piperidine and morpholine.Enol acetates (96) are prepared by refluxing with acetic anhydride-sodium acetate or by exchange with isopropenyl acetate in pyridine.Reaction with acetic anhydride catalyzed by boron trifluoride-etherate or perchloric acid gives the aldehyde diacetate. 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

The tertiary 17) -hydroxyl group does not form bulky enol ethers and mixed acetals. However, tetrahydropyranyl ethers are obtained from 17a-ethynyl-17]3-hydroxy compounds. Tetrahydropyranyl ethers have also been prepared from tertiary 17a-hydroxyl groups. ... 

The enol acetates, in turn, can be prepared by treatment of the parent ketone with an appropriate reagent. Such treatment generally gives a mixture of the two enol acetates in which one or the other predominates, depending on the reagent. The mixtures are easily separable. An alternate procedure involves conversion of a silyl enol ether (see 12-22) or a dialkylboron enol ether (an enol borinate, see p. 560) to the corresponding enolate ion. If the less hindered enolate ion is desired (e.g., 126), it can be prepared directly from the ketone by treatment with lithium diisopropylamide in THE or 1,2-dimethoxyethane at —78°C. ... 

Twofold Michael additions have been utilized by the groups of Spitzner [2] and Hagiwara [3] to construct substituted bicyclo[2.2.2]octane frameworks. In Hagiwara s approach towards valeriananoid A (2-6) [4], treatment of trimethylsily-enol ether 2-2, prepared from the corresponding oxophorone 2-1, and methyl acrylate (2-3) with diethylaluminum chloride at room temperature (r.t.) afforded the bicyclic compound 2-4 (Scheme 2.2). Its subsequent acetalization allowed the selective protection of the less-hindered ketone moiety to provide 2-5, which could be further transformed into valeriananoid A (2-6). 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Nitration of the potassium enolates of cycloalkanones with pentyl nitrate81 or nitration of silyl enol ethers with nitronium tetrafluoroborate82 provides a method for the preparation of cyclic a-nitro ketones. Trifluoroacetyl nitrate generated from trifluoroacetic anhydride and ammonium nitrate is a mild and effective nitrating reagent for enol acetates (Eq. 2.41).83... 

An interestingly short total synthesis of quadrone was developed by Kende and coworkers who made application of Pd(II)-mediated cycloalkenylation of silyl enol ethers (Scheme LV) Their point of departure was 609 which was converted directly to 610, Reaction of this silyl enol ether with palladium acetate in acetonitrile gave predominantly 6JI which could be cyclized to 612. From this intermediate, it was possible to prepare the known keto acid. 

Treatment of chromium (III) acetylacetonate with acetic anhydride and boron trifluoride etherate yielded a complex mixture of acetylated chelates but very little starting material. Fractional crystallization and chromatographic purification of this mixture afforded the triacetylated chromium chelate (XVI), which was also prepared from pure triacetylmethane by a nonaqueous chelation reaction (8, 11). The enolic triacetylmethane was prepared by treating acetylacetone with ketene. The sharp contrast between the chemical properties of the coordinated and uncoordinated ligand is illustrated by the fact that chromium acetylacetonate does not react with ketene. 

A short access to retinal was reported by Duhamel et al. [54,55] via the enolate of prenal, prepared from the corresponding silyl enol ether or enol acetate. The diene reacted with P-ionylideneacetaldehyde to give the dihydropyranol as the single reaction product. The dihydropyranol was... 

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