钯催化Heck反应和钌催化烯烃氧化裂解反应合成氮杂二氢色原酮

doi:10.6023/cjoc202511020

研究论文

钯催化Heck反应和钌催化烯烃氧化裂解反应合成氮杂二氢色原酮

崔入文^a,b, 刘晓倩^b, 杨亚玺^c, 陈超^*,b,c, 周兵^*,a,b,c

^a安徽中医药大学合肥 230012;
^b烟台新药创制山东省实验室,中科环渤海(烟台)药物高等研究院烟台 264117;
^c原创新药研究全国重点实验室,中国科学院上海药物研究所上海 201203

收稿日期:2025-11-26 修回日期:2026-01-09
基金资助:
山东省重点研发计划资助、中国科学院战略性先导科技专项资助(XDB1260102); 山东省自然科学基金 (ZR2024QH472, ZR2023LSW003); 山东省实验室项目 (SYS202205)资助项目.

Syntheses of azachromanones based on palladium-catalyzed Heck reaction and ruthenium-catalyzed oxidative cleavage of olefins

Ruwen Cui^a,b, Xiaoqian Liu^b, Yaxi Yang^c, Chao Chen^*,b,c, Bing Zhou^*,a,b,c

^aAnhui University of Chinese Medicine, Hefei 2300122;
^bShandong Laboratory of Yantai Durg Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117;
^cState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Received:2025-11-26 Revised:2026-01-09
Contact: ^*E-mail: zhoubing@simm.ac.cn; cchen@baridd.ac.cn
Supported by:
Key R&D Program of Shandong Province; the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB1260102); Shandong Provincial Natural Science Foundation (ZR2024QH472, ZR2023LSW003); Shandong Laboratory Program (SYS202205).

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摘要/Abstract

氮杂二氢色原酮是活性化合物中重要的结构单元,也是药物化学中的优势骨架。高效合成氮杂二氢色原酮的方法开发对于加速活性药物分子的发现具有重要意义,然而,现有的合成方法还存在操作繁琐、反应条件苛刻等不足。本研究利用钯催化的高区域选择性Heck反应 (Exo:Endo > 20:1)结合钌催化的温和烯烃氧化裂解反应,实现了氮杂二氢色原酮衍生物的高效合成。该方法具有反应条件温和、底物适用范围广、安全性良好和能够“一锅法”连续合成等优势,为氮杂二氢色原酮的合成提供了新策略。

关键词: 氮杂二氢色原酮, Heck反应, 区域选择性, 烯烃氧化裂解

Azachromanone represents an important structural motif among bioactive compounds and serves as a privileged scaffold in medicinal chemistry. The development of efficient synthetic approaches to azachromanones is highly desirable for accelerating the discovery of active drug molecules. However, existing synthetic methods still suffer from drawbacks such as cumbersome operations and harsh reaction conditions. In this study, an efficient synthesis of azachromanone derivatives was achieved through a palladium-catalyzed highly regioselective Heck reaction (Exo:Endo > 20:1) combined with a ruthenium-catalyzed mild olefin oxidative cleavage reaction. This method features mild reaction conditions, broad substrate scope, good safety, and the capability for consecutive one-pot synthesis, providing a new synthetic strategy for the construction of azachromanones.

Key words: azachromanone, Heck reaction, regioselectivity, oxidative cleavage of alkenes

引用此文

崔入文, 刘晓倩, 杨亚玺, 陈超, 周兵. 钯催化Heck反应和钌催化烯烃氧化裂解反应合成氮杂二氢色原酮[J]. 有机化学, doi: 10.6023/cjoc202511020.

Ruwen Cui, Xiaoqian Liu, Yaxi Yang, Chao Chen, Bing Zhou. Syntheses of azachromanones based on palladium-catalyzed Heck reaction and ruthenium-catalyzed oxidative cleavage of olefins[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202511020.

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