烯醇硅醚(Silyl enol ether)是烯醇醚中氧原子上的基团为硅基取代形成的一类化合物，是烯醇的稳定形式。最常见的硅基有三甲基硅(TMS)和叔丁基二甲基硅(TBDMS)。烯醇硅醚应用广泛，例如，它可以与卤代烃发生α烷基化反应[1]：

与卤代试剂反应制备α卤代酮[2]：

与醛酮反应制备α羟基化合物(Mukaiyama反应)[3]：

被mCPBA氧化制备α羟基酮(Rubottom反应)[4]：

利用烯醇硅醚保护羰基，通过选择合适的条件，可以形成热力学控制(取代基多)或者动力学控制(取代基少)的产物，进而活化不同的α位；此外，有时利用烯醇硅醚保护羰基，可以避免使用强碱带来的交叉偶联等副反应，所以烯醇硅醚是有机合成中的重要中间体。

烯醇硅醚一般由用含硅-卤键的化合物(如氯硅烷)与醛、酮在碱存在下反应或捕获醛、酮去质子化生成的烯醇负离子得到。根据使用的碱的强弱，可以控制所形成的双键的位置如：在 Et3N / DMF 体系中，用醛酮与 TMSCl 反应生成三甲硅烯醇醚，用叔丁基二甲基氯硅烷也可以得到相应的叔丁基二甲基硅基烯醇醚。不对称酮与三甲基硅基化合物作用时产生两种烯醇硅醚的混合物，并以热力学控制产物即较稳定的多取代烯烃为主要产物[5]:

对于有些酮类如樟脑就不能用三甲基氯硅烷，而需要采用三氟甲磺酸三甲硅基酯(CF3SO3SiMe3)作为生成烯醇硅醚的试剂[6]：

用非亲核性的强碱如LDA或NaHMDS，与酮作用生成相应的烯醇负离子，并用 TMSCl 捕获它制得烯醇硅醚。如果酮是不对称酮，则主要生成动力学控制的产物[7]：

烯醇硅醚一般在酸(如盐酸、三氟乙酸、对甲基苯磺酸和三氟化硼-乙醚)或者氟化物(CsF和TBAF等)处理下可再生得到羰基，硅基不同其稳定性也有差异，一般位阻大酸稳定性更好。

烯醇硅醚一般由含有α氢的醛酮与含硅-卤键的化合物(常见的如TMSCl,TBDMSCl, TMSOTf)在碱存在下得到。含多个羰基的化合物，根据其活性和形成烯醇硅醚稳定性差异，选择性的保护一个羰基是可能的。其脱除一般在酸或者氟化物作用下脱除，如果分子中含有其他酸性敏感的保护基(如Boc和缩醛等)，选择合适的条件选择性脱除硅醚也是可能的。常见的保护和脱保护典型操作如下：

应用举例1

To a solution of ketone (7.80 g,34.2 mmol) in dry toluene (140 mL) under a N2 atmosphere was added dry TEA (7.5 mL, 53.8 mmol) followed by chlorotrimethylsilane (6.5 mL, 51.5mmol) and the mixture stirred overnight. The reaction was quenched with sat.NaHCO3 (40 mL), the aqueous layer extracted with n-hexane (50 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuum to afford the title compound as colorless oil (9.3 g, 91%). (S. Kevin, B. David,Tetrahedron, 2012,68, 1017)

应用举例2

A solution of nBuLi (1.42 mL, 1.6 M in hexanes, 2.27 mmol,1.2 equiv) was added dropwise to a solution of iPr2NH (345 uL, 2.46mmol, 1.3 equiv) in THF (3 mL) at 0 °C. After 15 min, the LDA solution was cooled to -78 °C, and a solution of ketone (495 mg, 1.89 mmol) in THF (3 mL) was transferred via cannula. The resulting mixture was stirred 30min at -78 °C, and then TBSOTf(651 μL, 2.84 mmol, 1.5 equiv) was added. The resulting mixture was allowed to warm slowly to 0 °C and then quenched with saturated aqueous NaHCO3. The layers were separated, and the aqueous phase was extracted using petroleum ether. The combined organic phases were dried over MgSO4 and concentrated to a colorless oil, which was purified by column chromatography (eluent petroleum ether/Et2O/Et3N98/1/1) to give pure 2 (582 mg, 82%): Rf = 0.75 (petroleum ether/Et2O 95/5); colorlessoil. (N. M. Ahmad, V. Rodeschini, J. Org.Chem., 2007, 72, 4803)

应用举例3

A solution of silyl enol ether (6.58 g, 11.4 mmol) in THF (90 mL) at 0 oC was treated with a 1 M solutionof TBAF in THF neutralized with TsOH.H2O (11.4 mL). The resulting mixture was stirred for 10 min and diluted with Et2O (150 mL). The organic layer was then washed with H2O (2*70 mL), brine (70 mL), and dried over MgSO4. The solvent was removed under reduced pressure, and the resulting oil was purified by flash chromatography (EtOAc/hexanes, 1:2) to give ketone in 90% yield (4.75 g).(C. Fontana, M. Incerti, G. Moyna, Tetrahedron: Asymmetry., 2010,21, 398)

【参考文献】

[1] N. Yoshihiro, Y. Makoto,B. Akio, Org.Lett., 2007, 9, 4931.

[2] C. Xavier. J. Org. Chem., 1980, 45, 2419.

[3] A. J. Derek, D. Prabani, A. J. Matthew, Moleculers, 2012, 17, 2073.

[4] C. Xavier, G. C. Cristina, J. Am.Chem. Soc., 1982, 104, 4151.

[5] H. Hisahiro, F. Masakazu, Tetrahedron,2011, 67, 4061.

[6] K. Yusuke, I.Takanori, S. Makoto, Org. Lett., 2012, 14, 3186.

[7] Y. F. Li, J. P. Cooksey, Synthesis, 2011, 22, 104.