Technical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis (IAS), School of Chemistry and Molecular Engineering, State Key Laboratory of Material-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 211816, P. R. China.
Institute of Material Physics & Chemistry, College of Science, Nanjing Forestry University, Nanjing 210037, P. R. China.
J Org Chem. 2022 Aug 19;87(16):11226-11230. doi: 10.1021/acs.joc.2c01086. Epub 2022 Jul 28.
Herein, we report a strategically novel method for the efficient construction of indole skeletons using 2-phenylisoxazol-5-ones as the starting material. This reaction proceeds via Brønsted acid-promoted α-iminyl cation generation by N-O bond cleavage and a subsequent intramolecular cyclization to afford 1-indole-3-carboxylic acid, which further undergoes decarboxylation to yield the final product. Control experiments show that N-O bond cleavage and intramolecular cyclization proceed so fast that the 1-indole-3-carboxylic acid could be isolated in high yields even after 5-10 min. The substrate scope of this transformation is broad, and the desired products are obtained in moderate to good yields. The transition-metal-free reaction condition, CO as the sole byproduct, and good practicability add to the synthetic potential of this transformation in the pharmaceutical and flavor industries.
在此，我们报告了一种使用 2-苯基异恶唑-5-酮作为起始原料高效构建吲哚骨架的策略性新方法。该反应通过 N-O 键断裂生成 Brønsted 酸促进的α-亚氨基阳离子，随后进行分子内环化，得到 1-吲哚-3-羧酸，进一步脱羧得到最终产物。对照实验表明，N-O 键断裂和分子内环化进行得非常快，即使在 5-10 分钟后，也可以以高产率分离得到 1-吲哚-3-羧酸。该转化的底物范围很广，中等至良好的产率得到了所需的产物。无过渡金属的反应条件、CO 作为唯一的副产物和良好的实用性增加了该转化在制药和香料工业中的合成潜力。
