点击上方蓝色文字进行关注
背景介绍
往期给大家介绍过如何高效上叔丁基（脱叔丁基容易，上叔丁基难！学会这个方法再也不用愁！）。本期小编就给大家介绍一种N-Boc保护氨基酸叔丁酯中如何选择性脱除叔丁酯，而不掉Boc的方法。小编相信该方法在氨基酸衍生物和多肽的合成中是非常有用的。采用Lewis酸CeCl3‚7H2O，搭配NaI可以高效脱除N-Boc保护氨基酸叔丁酯中的叔丁酯。
底物范围
一些列脂肪族羧酸叔丁酯和芳香族羧酸叔丁酯都能高效的脱除叔丁酯。羟基上的叔丁基也会被脱除。
图片来源：J. Org. Chem.
所有叔丁酯 N-Boc (S)-氨基酸衍生物在没有外消旋的情况下被选择性去保护。叔丁酯可以在其他官能团存在下被选择性裂解，例如丝氨酸的羟基（条目 6）；同样值得注意的是，叔丁酯可以在甲基酯存在下被选择性裂解（表 2，条目 9）。此外，从 NR-Boc-NHCbz-Lys 底物 5k中去除叔丁酯证明该条件与其它常用的氨基酸保护基团兼容，例如Cbz基团。
图片来源：J. Org. Chem.
显然，这种方法的简便性，试剂的低成本，以及与其它路易斯酸相比铈（III）氯化物的温和性质增强了该方法的吸引力。
反应机理推测
叔丁酯的裂解是通过铈选择性地与叔丁酯氧原子配位形成复合物2，然后经历水解生成羧酸3，释放叔丁基碳正离子。后者被碘离子的亲核攻击捕获，得到叔丁基碘化物4，可以通过GC-MS鉴定。
图片来源：J. Org. Chem.
实验操作
Representative Procedure for the CeCl3‚7H2O/NaI Cleavage of tert-Butyl Esters (Table 1, entry 3).
To a stirred suspension of tert-butyl benzoate (1c; 0.178 g, 1 mmol) and NaI (0.195 g, 1.3 mmol) in acetonitrile (10 mL) was added CeCl3‚ 7H2O (0.56 g, 1.5 mmol), and the resulting mixture was stirred for 5 h at reflux. The reaction progress was monitored by withdrawing aliquots which were analyzed by GLC, and the products were identified by GC-MS. The reaction mixture was diluted with ether and treated with 0.5 N HCl (15 mL). The organic layer was separated, and the aqueous layer was extracted with ether (4 × 25 mL). The combined organic layers were washed twice with aqueous saturated NaCl solution and dried over anhydrous Na2SO4, and the solvent was evaporated. The obtained acid was purified by column chromatography to give 0.11 g (90% yield) of benzoic acid as a white solid, which was identical to the commercial product.
General Procedure for the Selective Removal of a tertButyl Ester Group.
A suspension of CeCl3‚7H2O (1.5 mmol) and NaI (1.3 mmol) in acetonitrile (10 mL) was stirred for 24 h at refluxing temperature. After being cooled to room temperature, this mixture was treated with the tert-butyl ester N-Boc R-amino acid derivative (1 mmol), and the mixture was stirred at reflux temperature until TLC indicates complete removal of tert-butyl ester group. The reaction was quenched by adding 0.5 N HCl, and the solvent was removed in vacuo at room temperature. The crude material was dissolved in a suitable organic solvent and washed with water and and brine. After drying (Na2- SO4) and solvent removal, the obtained N-Boc protected R-amino acids were purified by column chromatography; yields are reported in Table 2.
扫码关注我们
分子实用合成
了解更多合成方法
点了在看的人都很有趣~
点击左下角“阅读原文”，了解更多
