Citation: Yan Ding, Feng Lv, Yue Chen, Zhe Liu, Yang Ma, Shiru Li, Dejing Yin, Jian Wen, Yong Rao, Ling Huang, Zengwei Lai. Brønsted acid-catalyzed asymmetric [3 + 3] cyclization of para-quinamines: Access to 6/6/6/6-fused tetracyclic 1,2,4-triazinanes[J]. Chinese Chemical Letters, ;2026, 37(11): 112288. doi: 10.1016/j.cclet.2025.112288 shu

Brønsted acid-catalyzed asymmetric [3 + 3] cyclization of para-quinamines: Access to 6/6/6/6-fused tetracyclic 1,2,4-triazinanes

Yan Ding ^{a, 1} ,
Feng Lv ^{a, 1} ,
Yue Chen ^{b, 1} ,
Zhe Liu ^{a, 1} ,
Yang Ma ^a ,
Shiru Li ^a ,
Dejing Yin ^c ,
Jian Wen ^a ,
Yong Rao ^{b, *,} ,
Ling Huang ^{b, *,} ,
Zengwei Lai ^{a, *,}

a.
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
b.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570200, China
c.
School of Biotechnology, Jiangnan University, Wuxi 214122, China

raoyong@hainanu.edu.cn

Linghuang@hainanu.edu.cn

2860879@sina.com

Received Date: 13 November 2025
Revised Date: 12 December 2025
Accepted Date: 15 December 2025
Available Online: 16 December 2025

Figures(6)

A highly enantioselective Brønsted acid-catalyzed [3 + 3] cyclization between p-quinamines and azomethine imines has been developed, providing efficient access to 6/6/6/6-fused tetracyclic 1,2,4-triazinanes bearing three nitrogen-containing stereocenters. This transformation proceeds under mild conditions mediated by a chiral phosphoric acid catalyst, affording products in up to 94% yield and 99% ee. The reaction exhibits broad substrate scope, tolerating diverse functional groups including alkyl, aryl, heteroaryl, and alkynyl substituents. The utility of this method is demonstrated through gram-scale synthesis and diverse downstream transformations, leading to structurally complex polycyclic and cage-like heterocyclic frameworks. This metal-free strategy not only complements existing metal-catalyzed enantioselective routes to 1,2,4-triazine derivatives but also established a new paradigm for asymmetric [3 + 3] cyclization of p-quinamines. Notably, evaluation of the antifibrotic activity of selected 1,2,4-triazinanes identified the derivative 10 as a promising candidate against liver fibrosis.
- para-Quinamines,
- Azomethine imines,
- Asymmetric cycloaddition,
- Brønsted acid catalysis,
- 1,2,4-Triazinanes
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