Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China.
Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Sciences, Ningbo University, Ningbo 315211, China.
Molecules. 2022 Dec 19;27(24):9042. doi: 10.3390/molecules27249042.
2-oxazolines are common moieties in numerous natural products, pharmaceuticals, and functional copolymers. Current methods for synthesizing 2-oxazolines mainly rely on stoichiometric dehydration agents or catalytic dehydration promoted by specific catalysts. These conditions either generate stoichiometric amounts of waste or require forcing azeotropic reflux conditions. As such, a practical and robust method that promotes dehydrative cyclization while generating no byproducts would be attractive to oxazoline production. Herein, we report a triflic acid (TfOH)-promoted dehydrative cyclization of -(2-hydroxyethyl)amides for synthesizing 2-oxazolines. This reaction tolerates various functional groups and generates water as the only byproduct. This method affords oxazoline with inversion of α-hydroxyl stereochemistry, suggesting that alcohol is activated as a leaving group under these conditions. Furthermore, the one-pot synthesis protocol of 2-oxazolines directly from carboxylic acids and amino alcohols is also provided.
2-恶唑啉是许多天然产物、药物和功能共聚物中常见的结构单元。目前合成 2-恶唑啉的方法主要依赖于化学计量的脱水剂或特定催化剂促进的催化脱水。这些条件要么产生化学计量的废物，要么需要强制共沸回流条件。因此，一种实用且稳健的方法，既能促进脱水环化，又不产生副产物，对于恶唑啉的生产将具有吸引力。在此，我们报告了三氟甲磺酸（TfOH）促进的-（2-羟乙基）酰胺的脱水环化反应，用于合成 2-恶唑啉。该反应可以耐受各种官能团，只生成水作为唯一的副产物。该方法得到的恶唑啉具有α-羟基立体化学的反转，这表明在这些条件下醇作为离去基团被激活。此外，还提供了一种直接从羧酸和氨基醇一锅法合成 2-恶唑啉的方法。
