Silyl enol ethers are generally prepared by reacting an enolizablecarbonyl compound with a silylelectrophile and abase, or just reacting anenolate with a silyl electrophile.[3] Since silyl electrophiles arehard and silicon-oxygen bonds are very strong, the oxygen (of the carbonyl compound or enolate) acts as thenucleophile to form a Si-O single bond.[3]
The most commonly used silyl electrophile istrimethylsilyl chloride.[3] To increase the rate of reaction,trimethylsilyl triflate may also be used in the place of trimethylsilyl chloride as a more electrophilic substrate.[4][5]
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.[6] For instance, when usinglithium diisopropylamide (LDA), a strong and sterically hindered base, at low temperature (e.g., −78°C), the kinetic silyl enol ether (with a less substituted double bond) preferentially forms due to sterics.[6][7] When usingtriethylamine, a weak base, the thermodynamic silyl enol ether (with a more substituted double bond) is preferred.[6][8][9]
Example synthesis of a kinetic silyl enol ether by reacting an unsymmetrical ketone with trimethylsilyl chloride and LDA at low temperature.Example synthesis of a thermodynamic silyl enol ether by reacting an unsymmetrical ketone with trimethylsilyl chloride and triethylamine. Two possible mechanisms are shown.
Alternatively, a rather exotic way of generating silyl enol ethers is via theBrook rearrangement of appropriate substrates.[10]
Silyl enol ethers are neutral, mild nucleophiles (milder thanenamines) that react with good electrophiles such asaldehydes (withLewis acid catalysis) andcarbocations.[11][12][13][14] Silyl enol ethers are stable enough to be isolated, but are usually used immediately after synthesis.[11]
Example alkylation of a silyl enol ether using a tertiary alkyl halide in the presence of the Lewis acidTiCl4.Example Michael reaction using a disubstituted enone and the silyl enol ether of acetophenone, catalyzed by the Lewis acidTiCl4 at low temperature.More example reactions of silyl enol ethers.
Reacting a silyl enol ether with PhSCl, a good and soft electrophile, provides a carbonyl compound sulfenylated at analpha carbon.[22][20] In this reaction, thetrimethylsilyl group of the silyl enol ether is removed by thechloride ion released from the PhSCl upon attack of its electrophilic sulfur atom.[20]
Hydrolysis of a silyl enol ether results in the formation of a carbonyl compound and adisiloxane.[23][24] In this reaction, water acts as an oxygen nucleophile and attacks the silicon of the silyl enol ether.[23] This leads to the formation of the carbonyl compound and atrimethylsilanol intermediate that undergoes nucleophilic substitution at silicon (by another trimethylsilanol) to give the disiloxane.[23]
Example hydrolysis of a silyl enol ether to give a carbonyl compound andhexamethyldisiloxane.
Cyclic silyl enol ethers undergo regiocontrolled one-carbon ring contractions.[25][26] These reactions employ electron-deficient sulfonyl azides, which undergo chemoselective, uncatalyzed [3+2] cycloaddition 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 enol ethers ofesters (−OR) orcarboxylic acids (−COOH) are calledsilyl ketene acetals[13] and have the general structureR3Si−O−C(OR)=CR2. These compounds are more nucleophilic than the silyl enol ethers ofketones (>C=O).[13]
^abcdeClayden, J., Greeves, N., & Warren, S. (2012). Silyl enol ethers. InOrganic chemistry (Second ed., pp. 466-467). Oxford University Press.
^Clayden, J., Greeves, N., & Warren, S. (2012). Nucleophilic substitution at silicon. InOrganic chemistry (Second ed., pp. 669-670). Oxford University Press.
^Jung, M. E., & Perez, F. (2009). Synthesis of 2-Substituted 7-Hydroxybenzofuran-4-carboxylates via Addition of Silyl Enol Ethers too -Benzoquinone Esters.Organic Letters,11(10), 2165–2167.doi:10.1021/ol900416x
^abcdChan, T.-H. (1991). Formation and Addition Reactions of Enol Ethers. InComprehensive Organic Synthesis (pp. 595–628). Elsevier.doi:10.1016/B978-0-08-052349-1.00042-1
^abClayden, J., Greeves, N., & Warren, S. (2012). Kinetically controlled enolate formation. InOrganic chemistry (Second ed., pp. 600-601). Oxford University Press.
^Clayden, J., Greeves, N., & Warren, S. (2012). Thermodynamically controlled enolate formation. InOrganic chemistry (Second ed., pp. 599-600). Oxford University Press.
^Clayden, J., Greeves, N., & Warren, S. (2012). Making the more substituted enolate equivalent: thermodynamic enolates. InOrganic chemistry (Second ed., p. 636). Oxford University Press.
^Clive, Derrick L. J. & Sunasee, Rajesh (2007). "Formation of Benzo-Fused Carbocycles by Formal Radical Cyclization onto an Aromatic Ring".Org. Lett.9 (14):2677–2680.doi:10.1021/ol070849l.PMID17559217.
^abClayden, J., Greeves, N., & Warren, S. (2012). Silyl enol ethers in aldol reactions. InOrganic chemistry (Second ed., pp. 626-627). Oxford University Press.
^abcClayden, J., Greeves, N., & Warren, S. (2012). Silyl enol ethers are alkylated by SN1-reactive electrophiles in the presence of Lewis acid. InOrganic chemistry (Second ed., p. 595). Oxford University Press.
^abcdClayden, J., Greeves, N., & Warren, S. (2012). Conjugate addition of silyl enol ethers leads to the silyl enol ether of the product. InOrganic chemistry (Second ed., pp. 608-609). Oxford University Press.
^abHouse, 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
^Matsuo, J., & Murakami, M. (2013). The Mukaiyama Aldol Reaction: 40 Years of Continuous Development.Angewandte Chemie International Edition,52(35), 9109–9118.doi:10.1002/anie.201303192
^Narasaka, K., Soai, K., Aikawa, Y., & Mukaiyama, T. (1976). The Michael Reaction of Silyl Enol Ethers with α, β-Unsaturated Eetones and Acetals in the Presence of Titanium Tetraalkoxide and Titanium Tetrachloride.Bulletin of the Chemical Society of Japan,49(3), 779-783.doi:10.1246/bcsj.49.779
^M. T. Reetz & A. Giannis (1981) Lewis Acid Mediated α-Thioalkylation of Ketones, Synthetic Communications, 11:4, 315-322,doi:10.1080/00397918108063611
^abcClayden, J., Greeves, N., & Warren, S. (2012). Reactions of silyl enol ethers with halogen and sulfur electrophiles. InOrganic chemistry (Second ed., pp. 469-470). Oxford University Press.
^Chibale, K., & Warren, S. (1996). Kinetic resolution in asymmetric anti aldol reactions of branched and straight chain racemic 2-phenylsulfanyl aldehydes: asymmetric synthesis of cyclic ethers and lactones by phenylsulfanyl migration.Journal of the Chemical Society, Perkin Transactions 1, (16), 1935-1940.doi:10.1039/P19960001935
^abcClayden, J., Greeves, N., & Warren, S. (2012). Hydrolysis of enol ethers. InOrganic chemistry (Second ed., pp. 468-469). Oxford University Press.
^Gupta, S. K., Sargent, J. R., & Weber, W. P. (2002). Synthesis and photo-oxidative degradation of 2, 6-bis-[ω-trimethylsiloxypolydimethylsiloxy-2′-dimethylsilylethyl] acetophenone.Polymer,43(1), 29-35.doi:10.1016/S0032-3861(01)00602-4
