Enol ethers reagent

The chemoselective desilylation of one of the two different silyi enoi ethers in 10 to give the monosilyl enol ether II is realized by the Pd-catalyzed reaction of Bu3SnF. The chemoselectivity is controlled by steric congestion and the relative amount of the reagent[7,8]. An interesting transformation of the 6-alkoxy-2,3-dihydro-6//-pyran-3-one 12 into the cyclopentenone derivative 13 proceeds smoothly with catalysis by Pd(OAc)2 (10 mol%)[9]. 

The synthesis of polymethines with dimethylene bridges starts with aUcychc ketones (31), ketals (32), and enamines (X = NR2), or enol ethers (X = OR) (33). They possess two activated centers, methine or methylene groups, which react with Vilsmeief s reagent to produce the corresponding dyes. 

The in situ cyanosilylation of p-an1saldehyde is only one example of the reaction which can be applied to aldehydes and ketones in general. - The simplicity of this one-pot procedure coupled with the use of inexpensive reagents are important advantages over previous methods. The silylated cyanohydrins shown in the Table were prepared under conditions similar to those described here. Enolizable ketones and aldehydes have a tendency to produce silyl enol ethers as by-products in addition to the desired cyanohydrins. The... 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Enol ethers (15) and mixed acetals (16) are readily obtained from secondary but not from tertiary alcohols, whereas tetrahydropyranyl ethers can be formed even from tertiary alcohols. This is a result of the greater steric requirements of the reagents (17) and (18) as compared to (19). 

Enol ethers are readily attacked in buffered medium by electrophilic reagents such as halogens, A -haloamides, perchloryl fluoride and organic peracids to give a-substituted ketones. Similarly, electrophilic attack on... 

Systems usually fluonnated by electropositive fluorine reagents include acti-vated alkenes (enol ethers, enol acetates, silyl enol ethers, and enamines), activated aromatic systems, certain slightly activated carbon-hydrogen bonds, and selected organometallics. 

FITS reagents), has undergone considerable development recently [141,142,143, 144, 14S. These compounds, available fromperfluoroalkyhodides (equation 76), are very effective electrophilicperfluoroalkylating agents They react with carban-lons, aromatic compounds, alkenes, alkynes, silyl enol ethers, and other nucleophiles under mild conditions to introduce the perfluoroalkyl moiety mto organic substrates (equation 77) (see the section on alkylation, page 446). 

Me3SiCH2C02Et, cat. Bu4N F, 25°, 1-3 h, 90% yield. This reagent combination allows the isolation of pure products under nonaqueous conditions. The reagent also converts aldehydes and ketones to trimethylsilyl enol ethers.The analogous methyl trimethylsilylacetate has also been used. " ... 

Reaction of estrone methyl ether with methyl Grignard reagent followed by Birch reduction and hydrolysis of the intermediate enol ether affords the prototype orally active androgen in the 19-nor series, normethandrolone (69). ° (Note that here again the addition of the methyl group proceeded stereoselectively by approach from the least hindered side.) The preparation of the ethyl homolog starts by catalytic reduction of mestranol treatment of the intermediate, 70, under the conditions of the Birch reduction and subsequent hydrolysis of the intermediate enol ether yields norethandrolone (71). ... 

Nitradon of the potassium enolates of cycloalkanones with pentyl n silyl enol ethers with nitroniiim tetraflnoroborate " provides a method for the preparadon of cydic ct-nitro ketones. Tnflnoroacetyl nitrate generated from tnflnoroacedc anhydnde and ammonium nitrate is a mild and effecdve nitradug reagent for enol acetates fEq. 2.411. ... 

Cyclic and acyclic silyl enol ethers can be nitrated with tetranitromethane to give ct-nitro ketones in 64-96% yield fEqs. 2.42 and 2.43. " The mechanism involves the electron transfer from the silyl enol ether to tetranitromethane. A fast homolydc conphng of the resultant cadon radical of silyl enol ether with NO leads tn ct-nitro ketones. Tetranitromethane is a neutral reagent it is commercially available or readdy prepared. " ... 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

Provided that the silanolate elimination proceeds with anti selectivity, it must be concluded, that the intermediate homoallylic alcohol has an anti configuration, and thus the reagent has an ( -configuration. Acidic hydrolysis of the enol ether leads to enones the overall sequence consists of a nucleophilic acroylation. This has also been applied in the total synthesis of the marine diterpene ( )-aplysin-2067. 

A Lewis acid is involved in the reaction media when RCu BF3 or R3Al is used to cleave an acetal or ketal framework, and the resulting enol ether contains a E double bond. This is quite reasonable, since the overall reaction proceeds in an anti-SN2 manner. When a v>- -SN2 process is involved, the formation of products containing a Z double bond is observed60 (Table 2). The reaction of alkyllithium reagents with a./J-ethylcnic acetals and ketals proceeds in a. H7i-SN2 manner without assistance of Lewis acids, giving mainly the Z-products61-63. 

Acylsilanes are most useful synthetic intermediates (1), providing, inter alia, controlled routes to silyl enol ethers. They are relatively unreactive towards nucleophilic reagents for both steric and electronic reasons. 

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. ... 

Vinylic lithium reagents (26) react with silyl peroxides to give high yields of silyl enol ethers with retention of configuration. Since the preparation of 26 from vinylic halides (12-37) also proceeds with retention, the overall procedure is a... 

Ketones and carboxylic esters can be a hydroxylated by treatment of their enolate forms (prepared by adding the ketone or ester to LDA) with a molybdenum peroxide reagent (MoOs-pyridine-HMPA) in THF-hexane at -70°C. The enolate forms of amides and estersand the enamine derivatives of ketones can similarly be converted to their a hydroxy derivatives by reaction with molecular oxygen. The M0O5 method can also be applied to certain nitriles. Ketones have also been Qc hydroxylated by treating the corresponding silyl enol ethers with /n-chloroperoxy-... 

Aldehydes and ketones RCOR react with oc-methoxyvinyllithium CH2= C(Li)OMe to give hydroxy enol ethers RR C(OH)C(OMe)=CH2, which are easily hydrolyzed to acyloins, RR C(OH)COMe. this reaction, the CH2=C(Li)OMe is a synthon for the unavailable H3C—C=0. The reagent also reacts with esters RCOOR to give RC(OH)(COMe=CH2)2- A synthon for the Ph—C=0 ion is PhC(CN)OSiMe3, which adds to aldehydes and ketones RCOR to give, after hydrolysis, the a-hydroxy ketones, RR C(OH)-COPh. °... 

Silyi enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in DMSO or certain other polar aprotic solvents." The reaction has been performed with R , R = hydrogen or alkyl, though best yields are obtained when r = r = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyi enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-Bp3-Et20," ceric ammonium nitrate," and lead tetraacetate." If R =0R (in which case the substrate is a ketene silyi acetal), dimerization with TiCU leads to a dialkyl succinate (34, r =0R)." ... 

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