近日，西华大学张晓梅团队报道了接力催化阻转选择性合成轴手性4-芳基-异噁唑并[5,4-b]吡啶。相关论文于2026年8月9日发表在《中国化学》杂志上。

杂联芳基阻转异构体是药物开发和不对称催化中一类极具价值的骨架。尽管在该类骨架的阻转选择性构建方面已取得重大进展，但探索多种新型杂联芳基阻转异构体的不对称合成仍具有迫切需求。

研究组报道了一种接力催化策略，用于一类新型轴手性杂联芳基化合物的阻转选择性合成。通过手性磷酸与硝酸银的接力催化，实现了α-(3-异吲哚啉酮基)炔丙醇与5-氨基异噁唑或5-氨基吡唑之间的[3+3]环化、随后开环及质子转移的阻转选择性级联反应。

该转化能够构建多种新型轴手性4-芳基-异噁唑并[5,4-b]吡啶，产率为20%~80%（中低等），对映选择性为38%~98%（中等至优异）。随后，通过X射线单晶结构分析确定了其中一个产物及中间体的绝对构型。一系列控制实验揭示了该级联反应机理，其中中心手性向轴手性的转化是建立阻转异构现象的关键步骤。

附：英文原文

Title: Atroposelective Synthesis of Axially Chiral 4-Aryl-isoxazolo[5,4-b]pyridines by Relay Catalysis

Author: Wenzhe Li, Jianfeng Cheng, Xinlei Long, Quntao Gu, Min Huang, Xiaomei Zhang

Issue&Volume: 2026-08-09

Abstract: Heterobiaryl atropisomers represent a kind of highly valuable scaffolds in drug development and asymmetric catalysis. Although significant progress has been made in atroposelective construction of such kind of scaffolds, exploration of asymmetric synthesis of diverse novel heterobiaryl atropisomers is still desirable. Herein, we report a relay catalytic strategy for the atroposelective synthesis of a kind of novel axially chiral heterobiaryls. By relay catalysis of chiral phosphoric acid and silver nitrate, an atroposelective cascade reaction involving [3+3] cyclization of α-(3-isoindolinonyl) propargylic alcohols with 5-aminoisoxazoles or 5-aminopyrazole followed by ring-opening and proton transfer has been accomplished. This transformation allowed the construction of various novel axially chiral 4-aryl-isoxazolo[5,4-b]pyridines with low to moderate yields (20%–80%) in moderate to excellent enantioselectivities (38%–98% ee). Afterward, the absolute configurations of one product and the intermediate were determined by X-ray crystal structural analyses. Subsequently, a series of control experiments revealed a cascade reaction mechanism in which the central-to axial chirality conversion is the key step of the establishment of the atropisomerism.

DOI: 10.1002/cjoc.70674

Source: https://onlinelibrary.wiley.com/doi/10.1002/cjoc.70674