A mild and selective method for the hydrolysis of esters with trimethyltin hydroxide
A mild and selective method for the hydrolysis of esters with trimethyltin hydroxide
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DOI：
10.1002/anie.200462207
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Safina, BS
中科院分区：
文献类型：
--
作者：
Nicolaou, KC;Estrada, AA;Safina, BS
2005Wiley-VCH Verlag GmbH&Co.KGaA，Weinheim www安格万特。德·安格鲁。化学。2005、117、1402-1406将生成的羧酸基连接到最接近的胶束受体烯烃。当发现Me3SnOH可以从Aldol产物11中裂解Evans恶唑烷酮手性助剂[5](11b)，以良好的产率得到羧酸11a时，该方法的范围进一步扩大(表2，条目7)。对于其他酯，该方法的通用性也被证明是相当好的，因为它成功地裂解了甲酯、乙酯、烯丙基和苯基酯，但对甲戊酸酯无效。底物12(条目8，表2)进一步说明了该方案在定量产率中裂解醋酸酯的效率。表2中的条目9-16证明了该方法的选择性。很明显，对于芳香族和脂肪族体系，甲酯优先于异丙酯和乙酯进行水解，产率较高。在这些反应中也会产生少量的二元酸；在这些情况下，这是异丙酯和乙酯对反应条件的部分敏感性的结果。在测试苄基对甲酯和烯丙基对甲酯的选择性时，发现没有明显的偏好性。在测试醋酸酯保护基团和甲酯之间的选择性时，结果各不相同。在活化酯17(表2，条目13)中，在标准的LiOH条件下，只得到醇(由醋酸酯裂解产生)或醇/羧酸产物。相反，在使用锡试剂时，甲酯在仲醋酸酯存在的情况下被选择性地水解。这导致了对基质18和19的进一步试验(表2，条目14和15)。化合物19在初级醋酸酯保护基团存在的情况下再次发生甲酯的选择性水解，而化合物18的醋酸酯保护基团没有发生水解而发生了定量的损失。这些观察结果可以归因于酚醋酸酯很容易被除去，这是由于酚类部分具有良好的离开基团性质。进一步补充这一新方法的是分离得到的羧酸产物的简便性。一般的检查程序包括粗制反应混合物的浓缩和乙酸乙酯的稀释。然后，根据底物的酸稳定性，用水KHSO4(0.01n)或HCl(5%)洗涤有机层三次。在大多数情况下，由于Me3SnOH在水[2c，6]中的高溶解度[2c，6](通过1H核磁共振光谱通常为Me3SnOH的2mol%)，该过程产生了几乎纯的羧酸样品。当需要更高纯度的材料时，可以通过进一步的水洗或硅胶层析来去除剩余的锡试剂。在最后的测试中，为了证明易于异构化的底物对Me3SnOH的最终耐受性，以市售的(R)-4-羟基苯甘氨酸[8]和(R)-Mosher酸氯为原料，在标准条件下(CH2Cl2，吡啶，0.258C)分四步合成了二氯苯甘氨酸衍生物22[7](表3)。对偶联产物22进行了1H核磁共振波谱分析，结果表明DR为96：4。然后在标准LiOH和LiOOH条件下进行了尝试的水解与Me3SnOH和三甲基硅酸钾一起使用，据报道，这种试剂可以促进氨基酸酯的温和、无异构化的水解。[10]在08℃下，将甲酯22(R，R/S，R96：4)的非对映异构体混合物暴露到1.1当量的LiOH 20分钟后，然后进行…
1404 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www. angewandte. de Angew. Chem. 2005, 117, 1402–1406 the resulting carboxylic acid group to the proximate Michaelacceptor olefin. The scope of this method was further expanded when it was discovered that Me3SnOH could cleave the Evans oxazolidinone chiral auxiliary [5](11 b) from aldol product 11 to afford carboxylic acid 11 a in good yield (Table 2, entry 7). The generality of the method with regards to other esters also proved to be quite good, as it was successful in cleaving methyl, ethyl, allyl, and benzyl esters, but ineffective toward pivaloate esters. Substrate 12 (entry 8, Table 2) further illustrates the efficiency of this protocol in cleaving acetate esters in quantitative yields. Entries 9–16 in Table 2 demonstrate the selectivity of this method. It is evident that the methyl ester is hydrolyzed preferentially over isopropyl and ethyl esters in good yield, for both aromatic and aliphatic systems. A small amount of diacid is also produced in these reactions; in these cases it is a consequence of the partial susceptibility of the isopropyl and ethyl esters to the conditions of the reaction. In testing the selectivity for benzyl versus methyl esters and allyl versus methyl esters, it was found that no significant preference prevailed. In testing the selectivity between acetate protecting groups and methyl esters, the results varied. In the activated ester 17 (Table 2, entry 13), under standard LiOH conditions, only the alcohol (arising from cleavage of the acetate) or alcohol/carboxylic acid products were obtained. In contrast, upon use of the tin reagent the methyl ester was hydrolyzed selectively in the presence of the secondary acetate. This led to further experimentation with substrates 18 and 19 (Table 2, entries 14 and 15). Compound 19 again underwent selective hydrolysis of the methyl ester in the presence of the primary acetate protecting group, whereas 18 underwent quantitative loss of its acetate protecting groups, without hydrolysis of the methyl ester. These observations can be attributed to the ease with which phenolic acetates are removed, owing to the good leaving-group nature of the phenolic moiety. Further complementing this new methodology is the ease with which the resulting carboxylic acid products are isolated. A general workup procedure involved concentration of the crude reaction mixture and redilution in ethyl acetate. The organic layer was then washed three times with either aqueous KHSO4 (0.01 n) or HCl (5%), depending on the acid lability of the substrate. In most cases, this procedure produced a virtually pure sample of the carboxylic acid owing to the high solubility of Me3SnOH in water [2c, 6](typically 2 mol% of Me3SnOH by 1H NMR spectroscopy). When materials of higher purity were required, the remaining tin reagent could be removed by further aqueous washes or silica gel chromatography.In a final test to demonstrate the definitive tolerance of epimerization-prone substrates to Me3SnOH, dichlorinated phenyl glycine derivative 22 [7](Table 3) was prepared in four steps from commercially available (R)-4-hydroxyphenylglycine [8] and (R)-Mosher acid chloride under standard conditions (CH2Cl2, pyridine, 0! 258C).[9] 1H NMR spectroscopic analysis of the resulting coupled product 22 indicated a dr of 96: 4. The attempted hydrolysis was then carried out under standard LiOH and LiOOH conditions, and with Me3SnOH and potassium trimethylsilanolate, a reagent reported to promote mild, epimerization-free hydrolysis of amino acid esters.[10] After exposure of the diastereomeric mixture of methyl esters 22 (R, R/S, R 96: 4) to 1.1 equivalents of LiOH for 20 min at 08C, followed by …