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Silyl enol ethers in
Alternatively, a rather exotic way of generating silyl enol ethers is via the Brook rearrangement of appropriate substrates.
Acyloins form upon organic oxidation with an electrophilic source of oxygen such as an oxaziridine or mCPBA.
In the 
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clay ...
are a class of organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
s that share a common functional group composed of an enolate bonded through its oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as we ...
end to an organosilicon group. They are important intermediates in organic synthesis.
Synthesis
Silyl enol ethers are generally prepared by reacting an enolizablecarbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containin ...
compound with a silyl electrophile and a base, or just reacting an enolate with a silyl electrophile.Clayden, J., Greeves, N., & Warren, S. (2012). Silyl enol ethers. In ''Organic chemistry'' (Second ed., pp. 466-467). Oxford University Press. Since silyl electrophiles are hard and silicon-oxygen bonds are very strong, the oxygen (of the carbonyl compound or enolate) acts as the nucleophile to form a Si-O single bond.
The most commonly used silyl electrophile is trimethylsilyl chloride. To increase the rate of reaction, trimethylsilyl triflate
Trimethylsilyl trifluoromethanesulfonate is a trifluoromethanesulfonate derivate with a trimethylsilyl R-group. It has similar reactivity to trimethylsilyl chloride, and is also used often in organic synthesis.
Illustrative reactions
A common ap ...
may also be used in the place of trimethylsilyl chloride as a more electrophilic substrate.
When using an unsymmetrical enolizable carbonyl compound as a substrate, the choice of reaction conditions can help control whether the kinetic or thermodynamic silyl enol ether is preferentially formed.Chan, T.-H. (1991). Formation and Addition Reactions of Enol Ethers. In ''Comprehensive Organic Synthesis'' (pp. 595–628). Elsevier. doi:10.1016/B978-0-08-052349-1.00042-1 For instance, when using lithium diisopropylamide (LDA), a strong and sterically hindered base, at low temperature (e.g., -78℃), the kinetic silyl enol ether (with a less substituted double bond) preferentially forms due to sterics.Clayden, J., Greeves, N., & Warren, S. (2012). Kinetically controlled enolate formation. In ''Organic chemistry'' (Second ed., pp. 600-601). Oxford University Press. When using triethylamine, a weak base, the thermodynamic silyl enol ether (with a more substituted double bond) is preferred.
Alternatively, a rather exotic way of generating silyl enol ethers is via the Brook rearrangement of appropriate substrates.
Reactions
General reaction profile
Silyl enol ethers are neutral, mild nucleophiles (milder than enamines) that react with good electrophiles such asaldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...
s (with Lewis acid catalysis) and carbocations.Clayden, J., Greeves, N., & Warren, S. (2012). Silyl enol ethers in aldol reactions. In ''Organic chemistry'' (Second ed., pp. 626-627). Oxford University Press.Clayden, J., Greeves, N., & Warren, S. (2012). Silyl enol ethers are alkylated by SN1-reactive electrophiles in the presence of Lewis acid. In ''Organic chemistry'' (Second ed., p. 595). Oxford University Press.Clayden, J., Greeves, N., & Warren, S. (2012). Conjugate addition of silyl enol ethers leads to the silyl enol ether of the product. In ''Organic chemistry'' (Second ed., pp. 608-609). Oxford University Press. Silyl enol ethers are stable enough to be isolated, but are usually used immediately after synthesis.
Generation of lithium enolate
Lithium enolates, one of the precursors to silyl enol ethers, can also be generated from silyl enol ethers using methyllithium.House, H. O., Gall, M., & Olmstead, H. D. (1971). Chemistry of carbanions. XIX. Alkylation of enolates from unsymmetrical ketones. ''The Journal of Organic Chemistry'', ''36''(16), 2361–2371. doi:10.1021/jo00815a037 The reaction occurs vianucleophilic substitution
In chemistry, a nucleophilic substitution is a class of chemical reaction
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass c ...
at the silicon of the silyl enol ether, producing the lithium enolate and tetramethylsilane
Tetramethylsilane (abbreviated as TMS) is the organosilicon compound with the formula Si(CH3)4. It is the simplest tetraorganosilane. Like all silanes, the TMS framework is tetrahedral. TMS is a building block in organometallic chemistry but also ...
.
C–C bond formation
Silyl enol ethers are used in many reactions resulting inalkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...
, e.g., Mukaiyama aldol addition, Michael reactions, and Lewis-acid-catalyzed reactions with SN1-reactive electrophiles (e.g., tertiary
Tertiary ( ) is a widely used but obsolete term for the geologic period from 66 million to 2.6 million years ago.
The period began with the demise of the non- avian dinosaurs in the Cretaceous–Paleogene extinction event, at the start ...
, allylic, or benzylic alkyl halides). Alkylation of silyl enol ethers is especially efficient with tertiary alkyl halides, which form stable carbocations in the presence of Lewis acids like TiCl4 or SnCl4.
Halogenation and oxidations
Halogenation of silyl enol ethers gives haloketones.Clayden, J., Greeves, N., & Warren, S. (2012). Reactions of silyl enol ethers with halogen and sulfur electrophiles. In ''Organic chemistry'' (Second ed., pp. 469-470). Oxford University Press.
Acyloins form upon organic oxidation with an electrophilic source of oxygen such as an oxaziridine or mCPBA.
In the Saegusa–Ito oxidation
The Saegusa–Ito oxidation is a chemical reaction used in organic chemistry. It was discovered in 1978 by Takeo Saegusa and Yoshihiko Ito as a method to introduce α-β unsaturation in carbonyl compounds. The reaction as originally reported ...
, certain silyl enol ethers are oxidized to enones with palladium(II) acetate.
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Sulfenylation
Reacting a silyl enol ether with PhSCl, a good and soft electrophile, provides a carbonyl compound sulfenylated at an alpha carbon. In this reaction, the trimethylsilyl group of the silyl enol ether is removed by thechloride
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride s ...
ion released from the PhSCl upon attack of its electrophilic sulfur atom.
Hydrolysis
Hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysis ...
of a silyl enol ether results in the formation of a carbonyl compound and a disiloxane.Clayden, J., Greeves, N., & Warren, S. (2012). Hydrolysis of enol ethers. In ''Organic chemistry'' (Second ed., pp. 468-469). Oxford University Press. In this reaction, water acts as an oxygen nucleophile and attacks the silicon of the silyl enol ether. This leads to the formation of the carbonyl compound and a trimethylsilanol intermediate that undergoes nucleophilic substitution at silicon (by another trimethylsilanol) to give the disiloxane.
Ring contraction
Cyclic silyl enol ethers undergo regiocontrolled one-carbon ring contractions.Mitcheltree, M. J.; Konst, Z. A.; Herzon, S. B. ''Tetrahedron'' 2013, ''69'', 5634. These reactions employ electron-deficient sulfonyl azides, which undergo chemoselective, uncatalyzed +2cycloaddition to the silyl enol ether, followed by loss of dinitrogen, and alkyl migration to give ring-contracted products in good yield. These reactions may be directed by substrate stereochemistry, giving rise to stereoselective ring-contracted product formation.Silyl ketene acetals
Silyl enol ethers ofester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
s or carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...
s are called silyl ketene acetals. These compounds are more nucleophilic than the silyl enol ethers of ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...
s.
References