Citation: Fujie Liu, Yuzhu Yan, Xi Wang, Lingfei Hu, Gang Lu, Tao Xu. Retro aza-[2+2] cycloaddition as stereochemical editing logic for multi-substituted azacyclobutanes[J]. Chinese Chemical Letters, ;2026, 37(3): 111498. doi: 10.1016/j.cclet.2025.111498 shu

Retro aza-[2+2] cycloaddition as stereochemical editing logic for multi-substituted azacyclobutanes

Fujie Liu ^a ,
Yuzhu Yan ^a ,
Xi Wang ^a ,
Lingfei Hu ^b ,
Gang Lu ^b ,
Tao Xu ^{a, *,}

a.
Molecular Synthesis Center & Key Laboratory of Marine Drugs, MOE, School of Medicine and Pharmacy & Qingdao Marine Science and Technology Center, Ocean University of China, Qingdao 266003, China
b.
School of Chemistry and Chemical Engineering, Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Shandong University, Ji'nan 250100, China

xutao@ouc.edu.cn

Received Date: 23 February 2025
Revised Date: 13 June 2025
Accepted Date: 23 June 2025
Available Online: 24 June 2025

Figures(7)

Multi-substituted azetidines have been an under-utilized bioisosteres in modern drug entities, due to the scarcity of mild and stereo-controllable synthetic methods. The state-of-art aza-[2 + 2] cycloaddition suffers from two drawbacks, namely limited C=N scope and the dearth of stereochemical control. Herein, we extend a photocatalytic direct N-heteroarene dearomative aza-[2 + 2] cycloaddition under white light via energy transfer mechanism. A key protonic solvent triggered retro aza-[2 + 2] cycloaddition process was discovered and utilized as a stereochemical editing logic to address the challenge of diastereomeric control (controlling three contiguous stereocenters).
- Dearomatization,
- Retro aza-[2 + 2] cycloaddition,
- Azacyclobutane,
- Visible light catalysis
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