CeCl3•7H2O/NaI 促进叔丁基酯的脱保护

在有机合成中,区别于甲酯和乙酯这种常见的酯的碱性水解，有机化学家们对叔丁酯这种酸性状态下水解的酯也进行了广泛而有趣的研究，尤其是当化合物上有对碱性环境敏感的基团时，这种保护是必要的。

目前对叔丁酯脱除的主流方法有两种，一种以三氟乙酸为代表，一种以HCl为代表，两者有个共性，那便是反应体系酸性太强，对底物不是很友好，这迫使有机化学家们寻求更好的方法。

CeCl3 与传统的路易斯酸相比, 具有耐水、低毒和廉价易得等优点, 能够在温和的反应条件下有效地促进多种有机反应的顺利进行, 2001年，Marcantoni 团队首次报道了运用CeCl3·7H2O/NaI 来促进叔丁基酯的脱保护，文章发表在J Org Chem 2001, 66 (12), 4430-4432。

由于验证脱除叔丁基后的氨基酸在加热回流状态会和碘化钠反应原位生成碘化氢，根据底物的不同，文章给出了两种投料方式。

对于底物没有Boc基团时示例如下：

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.

对于底物含Boc基团选择性脱除示例如下：

 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 α-amino acid  (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 (Na2SO4) and solvent removal, the obtained N-Boc protected α-amino acids were purified by column chromatography; yield 75%.

以上方法可以套用到比较复杂的底物，示例如下：