2.5 三甲基硅乙氧羰基（Teoc）
三甲基硅乙氧羰基(Teoc)同前面提到的Cbz、Boc, Fmoc 和Alloc不同，它对酸、大部分碱，及贵金属催化等都很稳定，在它的存在下，Cbz、Boc，Fmoc和Alloc等可选择性去保护，而它的脱去则通常在氟负离子进行。如TBAF[1]、TEAF和HF[2]等。另外，TFA也可选择性去保护三甲基硅乙氧羰基[3]。
1. Seth, Punit P; Ray, Robinson, Dale E et al Bioorg. Med. Chem. Lett., 2004, 14(22), 5569-5572; Olsen, Christian A; Joergensen, Malene R et al Eur. J. Org. Chem., 2003, 17, 3288-3299; Boger, Dale L; Kim, Seong Heon et al J. Am. Chem. Soc., 2001, 123(9), 1862-1871
2. Tius, Marcus A; Thurkauf, Andrew; Tetrahedron Lett., 1986, 27(38), 4541-4544 3. Park, Haengsoon; Cao, Bin et al J. Org. Chem., 2001, 66(21), 7223-7226
2.5.1三甲基硅乙氧羰基（Teoc）的引入
Teoc-Cl[1, 2]、Teoc-OSu[2]或Teoc-OBt[3]在有机溶剂，碱的存在下同氨基化合物反应则可得到Teoc保护的氨基衍生物。
RNH2+ClOOTeoc ClTMSORNHOTMSBu4N.FRNH2RNHTeoc
1. Zubert, Sheena; Glen, Angela et al Tetrahedron Lett. 1998, 39(41), 7567-7570; Trost, Barry M; Cossy, Janine; J. Am. Chem. Soc., 1982, 104(24), 6881-6882; Sulline, David W; Bobik, Thomas A et al J. Am. Chem. Soc., 1993, 115(15), 6646-6651 2. Shute, Richard; Rich, Daniel H; Synthesis, 1987, 4, 346-349
3. Boger, Dale L; Kim, Seng Heon et al., J. Am. Chem. Soc., 2001, 123(9), 1862-1871; Boger, Dale L;
Kim, Seng Heon et al., J. Am. Chem. Soc., 2000, 122(30), 7416-7417
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2.5.1.1 Teoc-Cl引入三甲基硅乙氧羰基(Teoc)示例
SiOOClOH2N1OHOTeocHN2OHaq. NaHCO3, dioxane
Shute, Richard; Rich, Daniel H; Synthesis, 1987, 4, 346-349
NaHCO3(3.78 g, 45 mmol) and compound 1(15 mmol) are added to water (15 ml) and the mixture is stirred at room temperature for 30 min or until the majority of the solids dissolve. To this suspension is added a solution of Teoc-Cl in dioxane (30 ml). The resultant mixture is stirred vigorously at room temperature overnight, poured into water (50 ml) and extracted with ether (3 x 50 ml), the organic extracts being discarded. The aqueous layer is acidified to Ph = 2 with saturated potassium hydrogen sulfate solution and extracted with ether (3 x 50 ml). The combined organic extracts are washed with water (3 x 75 ml), dried with MgSO4, and evaporated to give compound 2 ().
2.5.1.2 Teoc-OSu引入三甲基硅乙氧羰基(Teoc)示例1
OSiOHONH2O1OHOOONOOHOOHOEt3N, dioxane, H2OTeocNH2
Shute, Richard; Rich, Daniel H; Synthesis, 1987, 4, 346-349
To a stirred suspension of compound 1 (0.13 g, 1 mmol) in water (1 ml) is added a solution of triethylamine (0.26 g, 2.6 mmol) in dioxane (1 ml). To the resultant solution is added solid Teoc-OSu (0.29 g, 1.1 mmol). The mixture is stirred at room temperature overnight, then diluted with water (5 ml), acidified with saturated potassium hydrogen sulfate solution, and extracted with ether (3 x 15 ml). The combined organic layers are washed with water (4 x 20 ml), dried with MgSO4, and evaporated to afford compound 2 (0.23 g, 84%) as an oily residue.
Teoc-OSu引入三甲基硅乙氧羰基(Teoc)示例2
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OSiOHONH2O1OHOOONOOHOOHOEt3N, dioxane, H2OTeocNH2
Shute, Richard; Rich, Daniel H; Synthesis, 1987, 4, 346-349
To a stirred suspension of compound 1 (0.13 g, 1 mmol) in water (1 ml) is added a solution of triethylamine (0.26 g, 2.6 mmol) in dioxane (1 ml). To the resultant solution is added solid Teoc-OSu (0.29 g, 1.1 mmol). The mixture is stirred at room temperature overnight, then diluted with water (5 ml), acidified with saturated potassium hydrogen sulfate solution, and extracted with ether (3 x 15 ml). The combined organic layers are washed with water (4 x 20 ml), dried with MgSO4, and evaporated to afford compound 2 (0.23 g, 84%) as an oily residue.
OO2NF1NH2OMeSiOOONNNTeoc-OBt引入三甲基硅乙氧羰基(Teoc)示例
OO2NF2OMeNHTeocEt3N, dioxane, H2O
Boger, Dale L; Kim, Seng Heon et al., J. Am. Chem. Soc., 2001, 123(9), 1862-1871; Boger, Dale L; Kim, Seng Heon et al., J. Am. Chem. Soc., 2000, 122(30), 7416-7417
To a stirred suspension of compound 1 (0.24 g, 1 mmol) in water (1 ml) is added a solution of triethylamine (0.26 g, 2.6 mmol) in dioxane (1 ml) followed by solid Teoc-Bt (0.31 g, 1.1 mmol). The mixture is stirred at room temperature overnight, then diluted with water (5 ml), acidified with saturated potassium hydrogen sulfate solution, and extracted with ether (3 x 15 ml). The combined organic layers are washed with water (4 x 20 ml), dried with MgSO4, and evaporated to afford compound 2 (0.36 g, 92%).
2.5.1.4一般氨基的三甲基硅乙氧羰基（Teoc）的引入示例
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OOClSiNH21NHTeoc2DIPEA, DMAPCH2Cl2
Mueller, Paul; Imogai, Hassan; Tetrahedron: Asymmetry, 1998, 9(24), 4419-4428 To compound 1 (486 mg, 8.5 mmol) in CH2Cl2 (15 mL) was added, at ?10°C, diisopropylethylamine (1.72 g, 17 mmol) followed by Teoc-Cl (3.06 g, 17 mmol) in CH2Cl2, and finally, dimethylaminopyridine (DMAP, 30 mg). The mixture was stirred overnight, then hydrolyzed with satd NaHCO3, and extracted with CH2Cl2 (3 x 30 mL) at 0°C and satd Na2CO3. After drying and evaporation of the solvent, the crude product was purified by chromatography (SiO2; hexane:AcOEt = 85:5) and afforded compound 2 (1.49 g, 88%) as a colorless liquid.
2.5.2三甲基硅乙氧羰基（Teoc）的脱去
一般三甲基硅乙氧羰基(Teoc)脱除主要通过TBAF(四丁基氟化胺)，TEAF (四乙基氟化胺)或TMAF(四甲基氟化胺)来脱除，在脱除过程中，TBAF将产生四丁基胺盐的副产物，常常不易除去，而且它的质谱丰度高，往往影响产品的交货，此时可用TMAF或TEAF来代替。
2.5.2.1三甲基硅乙氧羰基（Teoc）的脱去示例
OOOMeMeO1OOOOHOOPO2NHTeocTBAFTHFMeOOMeOOOOOHOPONH2
Gugiu, Bogdan G; Salomon, Robert G; Org. Lett., 2003, 5(16), 2797-2800
Compound 1 (33 mg, 0.042 mmol) was dissolved in THF and TBAF (0.070 mL 1M in THF containing 18.4 mg, 0.070 mmol) was added, and the solution stirred at room temperature for 48 h under argon following the disappearance of compound 1 by TLC (36 h). After the removal of solvent by rotary evaporation under low pressure the product was purified by flash chromatography using CHCl3/MeOH/H2O (60:38:2) to give compound 2 (20 mg, 72%) with Rf = 0.53 in CHCl3/MeOH/H2O (60:38:2).
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