Synthesis of N-Hydroxysuccinimide Esters, N-Acylsaccharins, and Activated Esters from Carboxylic Acids Using I2/PPh3,The Journal of Organic Chemistry

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Synthesis of N-Hydroxysuccinimide Esters, N-Acylsaccharins, and Activated Esters from Carboxylic Acids Using I2/PPh3
The Journal of Organic Chemistry ( IF 3.3 ) Pub Date : 2024-05-28 , DOI: 10.1021/acs.joc.4c00272
Kishor L Handore ₁ , Heyuan Lu ₁ , Hyeongbin Park ₁ , Qingyu Xiong ₁ , Robert A Batey ₁

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A method for the syntheses of isolable, active esters is described in which carboxylic acids are treated with triphenylphosphine, iodine, and triethylamine. Active esters accessible in this way include N-hydroxysuccinimide esters, N-hydroxyphthalimide esters (N-(acyloxy)phthalimides), N-acylsaccharins, pentafluorophenol esters, pentachlorophenol esters, N-hydroxybenzotriazole esters, and hexafluoro-2-propanol esters. The approach can be similarly applied toward the formation of N-acylsaccharins and N-acylimidazoles. The method is suitable for the formation of isolable active esters of aromatic and aliphatic activated acids as well as α-amino acid derivatives. These products are widely used reagents in organic synthesis, peptide synthesis, medicinal chemistry, and chemical biology (e.g., for bioconjugations). The method has broad substrate scope, uses simple and inexpensive reagents, avoids the use of carbodiimides or other coupling agents, and occurs at room temperature. Additionally, the diastereomers of compound Boc-Ala–NHCHPh are demonstrated to be distinguishable by ¹H NMR (in DMSO-d₆), allowing for a straightforward NMR method to establish the degree of racemization of activated esters of Boc-Ala or amide bond formations using Boc-Ala.

中文翻译：

使用 I2/PPh3 从羧酸合成 N-羟基琥珀酰亚胺酯、N-酰基糖精和活化酯

描述了一种合成可分离的活性酯的方法，其中用三苯基膦、碘和三乙胺处理羧酸。以此方式可获得的活性酯包括N-羟基琥珀酰亚胺酯、 N-羟基邻苯二甲酰亚胺酯( N- (酰氧基)邻苯二甲酰亚胺)、 N-酰基糖精、五氟苯酚酯、五氯苯酚酯、 N-羟基苯并三唑酯和六氟-2-丙醇酯。该方法可以类似地应用于N-酰基糖精和N-酰基咪唑的形成。该方法适用于芳香族和脂肪族活化酸以及α-氨基酸衍生物的可分离活性酯的形成。这些产品广泛应用于有机合成、肽合成、药物化学和化学生物学（例如，用于生物共轭）。该方法底物范围广泛，使用的试剂简单廉价，避免使用碳二亚胺或其他偶联剂，并且在室温下进行。此外，化合物 Boc-Ala–NHCHPh 的非对映异构体被证明可以通过¹ H NMR（在 DMSO- d ₆中）区分，从而可以使用简单的 NMR 方法来确定 Boc-Ala 或酰胺键的活化酯的外消旋程度使用 Boc-Ala 编队。

更新日期：2024-05-28

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