微波辅助的分子内 Ullmann 二芳基醚化反应作为 Ugi 环加成反应之后的一环，用于构建二苯并[b,f][1,4]恶嗪骨架。

Microwave-Assisted Intramolecular Ullmann Diaryl Etherification as the Post-Ugi Annulation for Generation of Dibenz[b,f][1,4]oxazepine Scaffold.

机构信息

Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University , Hangzhou 310027, P. R. of China.

Laboratory of Advanced Catalysis and Synthesis, Department of Chemistry, The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon, Hong Kong SAR, P. R. of China.

出版信息

J Org Chem. 2016 Nov 4;81(21):10392-10403. doi: 10.1021/acs.joc.6b01398. Epub 2016 Aug 12.

DOI:10.1021/acs.joc.6b01398

PMID:27517309

Abstract

A sequence of the Ugi four-component reaction (U-4CR) and microwave-assisted intramolecular Ullmann etherification has been established for efficient generation of a dibenz[b,f][1,4]oxazepine scaffold. The U-4CR, using 2-aminophenols and 2-bromobenzoic acids or 2-bromobenzaldehydes as the inputs, was carried out in MeOH at 50-60 °C for 2-3 days to form a collection of 22 linear products in 46-90% yields. A microwave-assisted intramolecular Ullmann etherification was then used to transform these acyclic U-4CR products into the cleft-shaped 6/7/6-fused tricyclic heterocycles. The intramolecular Ullmann diaryl ether formation was catalyzed by 10 mol % of CuI and 30 mol % of N,N-dimethylglycine hydrochloride (DMG·HCl) in the presence of CsCO with microwave irradiation (150 °C, 30 min) to furnish dibenz[b,f][1,4]oxazepin-11(10H)-ones and dibenz[b,f][1,4]oxazepin-11(10H)-carboxamides in 64-100% yields.

摘要

已建立了 Ugi 四组分反应（U-4CR）和微波辅助分子内乌尔曼醚化的序列，用于高效生成二苯并[b,f][1,4]噁嗪骨架。U-4CR 使用 2-氨基酚和 2-溴苯甲酸或 2-溴苯甲醛作为反应物，在 MeOH 中于 50-60°C 下反应 2-3 天，以 46-90%的收率得到 22 个线性产物的混合物。然后，通过微波辅助分子内乌尔曼醚化将这些非环 U-4CR 产物转化为具有裂缝形状的 6/7/6 稠合的三环杂环。在 CsCO 的存在下，通过 10 mol%的 CuI 和 30 mol%的 N,N-二甲基甘氨酸盐酸盐（DMG·HCl）作为催化剂，通过微波辐射（150°C，30 分钟）进行分子内乌尔曼二芳基醚形成，以 64-100%的收率得到二苯并[b,f][1,4]噁嗪-11(10H)-酮和二苯并[b,f][1,4]噁嗪-11(10H)-甲酰胺。