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

doi:10.6023/cjoc202511020

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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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Abstract

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

Cite this article

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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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

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

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