Citation: Chenyang Guo, Huili Sun, Meng Shan, Tianyu Yang, Haohua Chen, Junbiao Chang, Bo Zhu. Pd-catalyzed asymmetric hydroalkylation of heterocycle-embedded dienes[J]. Chinese Chemical Letters, ;2026, 37(11): 112371. doi: 10.1016/j.cclet.2026.112371 shu

Pd-catalyzed asymmetric hydroalkylation of heterocycle-embedded dienes

Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, School of Pharmaceutical Sciences, Henan Normal University, Xinxiang 453007, China

chenhaohua@htu.edu.cn

changjunbiao@zzu.edu.cn

zbtiantang@126.com

Received Date: 9 September 2025
Revised Date: 29 December 2025
Accepted Date: 6 January 2026
Available Online: 7 January 2026

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The asymmetric hydroalkylation of conjugated dienes is a key strategy for the direct synthesis of chiral molecules. While notable progress has been made in the study of linear and branched dienes, research on the asymmetric hydroalkylation of conjugated dienes embedded in heterocyclic systems remains limited. Here we report for the first time the asymmetric hydroalkylation of heterocycle-embedded dienes. Using palladium and a chiral urea-phosphine ligand, a series of chiral coumarin derivatives with adjacent chiral centers were synthesized with excellent enantioselectivity, diastereoselectivity, and regioselectivity. Furthermore, the reaction is scalable and adaptable, and the resulting coumarin derivatives exhibit selective antitumor activity. The enantiocontrol model is proposed based on density functional theory (DFT) results, where the bifunctional ligand plays a crucial role in this enantioselective control.
- Asymmetric hydroalkylation,
- Palladium,
- Heterocycle-embedded dienes,
- Azlactones,
- Bifunctional ligand
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