Constructing Chiral Indanes by a Ligand Relay-Enabled Pd-Catalyzed Asymmetric [4+1] Annulation via Carbene Insertion/Tsuji-Trost Cascade

doi:10.6023/cjoc202603004

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (6): 2431-2441.DOI: 10.6023/cjoc202603004 Previous Articles Next Articles

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配体接力促进的钯催化卡宾插入/Tsuji-Trost串联反应实现不对称[4+1]环化构筑手性茚满

张超^a, 罗洲^b, 赵申^b, 沈安^c^,^*(), 杨国强^b^,^*(), 刘媛媛^a^,^*()

^a 华东师范大学化学与分子工程学院上海 200062
^b 上海交通大学变革性分子前沿科学中心上海 200240
^c 上海化工研究院聚烯烃催化技术与高性能材料全国重点实验室上海 200062

收稿日期:2026-03-04 修回日期:2026-03-20 发布日期:2026-04-02
基金资助:
国家自然科学基金(22371073); 中央高校基本科研业务费专项资金(25X010202131); 聚烯烃催化技术与高性能材料全国重点实验室(SKLZX-2025-11)

Constructing Chiral Indanes by a Ligand Relay-Enabled Pd-Catalyzed Asymmetric [4+1] Annulation via Carbene Insertion/Tsuji-Trost Cascade

Chao Zhang^a, Zhou Luo^b, Shen Zhao^b, An Shen^c^,^*(), Guoqiang Yang^b^,^*(), Yuanyuan Liu^a^,^*()

^a School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062
^b Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240
^c State Key Laboratory of Polyolefins and Catalysis, Shanghai Research Institute of Chemical Industry Co., Ltd., Shanghai 200062

Received:2026-03-04 Revised:2026-03-20 Published:2026-04-02
Contact: * E-mail: yyliu@chem.ecnu.edu.cn;gqyang@sjtu.edu.cn;shenan@srici.cn
Supported by:
National Natural Science Foundation of China(22371073); Fundamental Research Funds for the Central Universities(25X010202131); State Key Laboratory of Polyolefins and Catalysis(SKLZX-2025-11)

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Abstract

Asymmetric annulation via palladium-carbene intermediates offers a powerful route to chiral cyclic frameworks, yet its development remains a significant challenge. Here, a Pd-catalyzed asymmetric [4+1] annulation for constructing chiral indanes is disclosed, enabled by a novel dynamic multiligand relay asymmetric catalysis. The ligand relay system employs a bidentate Pyrox ligand to promote the oxidative addition, while a monodentate Feringa-type phosphoramidite ligand facilitates the carbenation/migratory insertion step and the following intramolecular Tsuji-Trost reaction. The practical utility of this method was confirmed through a scale-up experiment. This strategy establishes a practical and efficient route to enantioenriched vicinal substituted indanes.

Key words: asymmetric catalysis, ligand relay, palladium catalysis, Tsuji-Trost reaction, carbene insertion

Cite this article

Chao Zhang, Zhou Luo, Shen Zhao, An Shen, Guoqiang Yang, Yuanyuan Liu. Constructing Chiral Indanes by a Ligand Relay-Enabled Pd-Catalyzed Asymmetric [4+1] Annulation via Carbene Insertion/Tsuji-Trost Cascade[J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2431-2441.

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Fig. & Tab. 6

Scheme 1. Pd-catalyzed 3FGC via metal carbenes

Figure 1. Representative natural products and drugs bearing chiral indane skeletons

Without L2

With L1a

Table 1. Ligand screening a

Table 2. Substrate scopea

Scheme 2. Gram-scale reaction and derivatization of product 3a

Scheme 3. Proposed catalytic cycle

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配体接力促进的钯催化卡宾插入/Tsuji-Trost串联反应实现不对称[4+1]环化构筑手性茚满

Constructing Chiral Indanes by a Ligand Relay-Enabled Pd-Catalyzed Asymmetric [4+1] Annulation via Carbene Insertion/Tsuji-Trost Cascade

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