Boc比Cbz对酸敏感，酸解产物为异丁烯和CO2（见下式）。在液相肽的合成中，Boc的脱除一般可用TFA或50%TFA（TFA:CH2Cl2= 1:1,v/v）。而在固相肽合成中，由于TFA会带来一些副反应（如在得到的胺上上一个三氟乙酰基等），因此多采用1-2MHCl/有机溶剂。一般而言用HCl/二氧六环，比较多见。
用甲醇作溶剂，HCl/EtOAc的组合使TBDMS和TBDPS酯[1]以及叔丁酯和非酚类酯在Boc脱除时不被断裂，而S-Boc除外[2]。但当同时脱除分子中Boc和叔丁酯, 或分子中有游离羧酸基，千万记住不能用HCl/MeOH,其可将羧酸变为甲酯。同时AcCl/MeOH，则是一个在甲醇中产生无水HCl的便利方法。这些条件也可用来从羧酸制备酯以及形成胺的盐酸盐[3]。
在中性的无水条件下Me3SiI在CHCl3或CH3CN中除了能脱除Boc外，也能断裂氨基甲酸酯、酯、醚和缩酮。通过控制条件可以得到一定的选择性[4]。
当分子中存在一些官能团其可与副产物叔丁基碳正离子在酸性下反应时，需要添加硫酚(如苯硫酚)来清除叔丁基碳正离子，如此举可防止蛋氨酸和色氨酸的脱Boc时的烷基化[5]。也可使用其它的清除剂，如苯甲醚、苯硫基甲醚、甲苯硫酚、甲苯酚及二甲硫醚[6]。在Boc脱去过程中TBDPS[7]和TBDMS[8]基对CF3COOH是稳定的（在TBS存在，用相对稀一些的10－20 ％TFA）。伯胺衍生物存在下，ZnBr2/CH2Cl2可以选择性的脱除仲胺上的Boc[9]
1. F. Cavelier, C.Enjabal., Tetrahedron Lett., 1996, 37, 5131
2. F. S. Gibson,S. C. Bergmeier, H. Rapoport., J. Org. Chem., 1994, 59, 3216
3. A.Nudelman, Y.Bechor et al., Synth. Commun., 1998, 28, 471
4. R. S. Lott, V.S. Chauhan et al., J. Chem. Soc. Chem. Commun., 1979, 495; G. A.Olah, S. C. Narang., Tetrahedron., 1982, 38, 2225
5. R. A. T. M. vanBenthem, H. Hiemstra et al., J. Org. Chem., 1992, 57, 6083
6. M. Bodanszky,A. Bodanszky., Int. J. Pept. Protein Res., 1984, 23, 565;Y. Masui, N. Chino et al., Bull. Chem. Soc. Jpn., 1980, 53,464
7. P. A. Jacobi,S. Murphree et al., J. Org. Chem., 1996, 61, 2413
8. J. Deng, Y.Hamada et al., J. Am. Chem. Soc., 1995, 117, 7824
9. S. C. Nigam, A. Mann et al., Synth. Commun.,1989, 19, 3139
反应实例
一、TMSOTf中性条件下脱Boc示例
Gilbertson, Scott R; Chang, Cheng-Wei et al., J.Org. Chem., 1998, 63(23), 8424-8431
To a solution containing 2 (1.0 g, 3.9 mmol) in 30 mL of dry CH2Cl2was slowly added TBDMSOTf (0.9 mL, 4.1 mmol). After stirring the reactionmixture for 6 h, the solvent was evaporated, and the crude product (0.8 g, 75%) was obtaineded, which was used directly inthe next step.
二、 TMSOTf-2,6-lutidine中性条件下脱Boc示例
Kemp, Scott J; Bao, Jiaming et al J. Org.Chem., 1996, 61(20), 7162-7167
To a stirring solution of compound 1 (800 mg, 2.0 mmol) and2,6-lutidine (0.4463 ml, 4.0 mmol) in CH2Cl2(6 mL) was added tert-butyldimethylsilyl triflate (0.690 ml, 3.0mmol) dropwise over 5 min. After 20 min, saturated NH4Cl (10 mL) wasadded. The mixture was stirred and separated, and the aqueous layer wasextracted with Et2O (3 x 15 mL). The combined organic layers were washedwith water (2 x 10 mL) and saturated NaCl (10 mL), dried (MgSO4), andconcentrated to give the crude silyl carbamate, which was dissolved inTHF (10 mL) and cooled to 0°C.A 1.0 M solution of TBAF in THF(2 mL, 2 mmol) was added over 5 min, and then the solution was stirred at 0°C for 1 h. The solution was concentratedand chromatographed (95:5 CH2Cl2-methanol) through a small plug of silica to give compound2 (882 mg, 75%) as a clear oil.
三、TFA脱Boc示例
M. Alberto; A. Eduardo et al., J. Org. Chem., 2004, 21,7004
To a solution ofthe β-aminoester (0.2 mmol) in CH2Cl2 (3 mL), cooled to 0°C was added TFA (1mL). After the consumption of the starting material (45 min, monitored by TLC), the mixture was evaporated and thensaturated aqueous NaHCO3 was added. The aqueous layer was extractedtwice with CH2Cl2 (15 mL), and the organic layer washedwith brine and dried over anhydrous Na2SO4. The solventwas removered under vacuum, to afford the amine, which were employed without further purification to prepare the Mosher’s diastereoisomeric amides.
四、HCl-THF脱Boc示例
J.Wehbe et al., Tetrahedron: Asymmetry, 2004, 15, 851
Tothe Boc protected amine (0.06 g,0.17 mmol) dissolved in THF (1mL) was added 2M HCl (1mL, 2 mmol) and the mixture stirred 2 h atroom temperature. After evaporation of the solvent, the product was extractedinto EtOAc (3.5mL).The organic layer was dried and evaporated under vacuum to afford 17b in 95% yield as a whitesolid.
五、叔丁酯存在下的脱Boc示例1
US5610144
1.77 ml of Me3SiIare added dropwise at room temperature in the vicinity of 25°C to a soution of 3.8 gof compound 1 in50 ml of CHCl3. Stirring is contiuned for 30 min, then 20 ml f waterare addede. The aqueous phase is separated, then extracted with CHCl3(2x 20 ml). The organic phases are combined, washed successively with a saturatedaqueous Na2CO3(30 ml) and water(2 x 30 ml), then driedover MgSO4 and concentrated to dryness under reduced pressure at 40°C. The mixture of the two diastereoisomersobtained is separated by chromatography on silica (eluent: ethylacetate/cyclohexane = 1/4). The fractions containing the expected product arecombined and concentrated to dryness under reduced pressure at 40°C to give compound 2 (0.5 g), as a yellow-orange oil, used as it isin subsequent syntheses.
六、叔丁酯存在下的脱Boc示例2
WO20040106286
To a solution of compound 1(149 mg, 0.33 mmol) in CH2Cl2 (2 ml), TFA (1 ml) as addedat 0°C and the mixture was stirred for 1 h at 0°C. Saturated aqueous Na2CO3was added and the mixture was etracted with CHCl3. The etract waspurified by silica gel column chromatography to obtained compound 2 (92mg, 79%).
本文非原创内容，版权归原作者所有。
