Efficient Construction of Nitrogen-Stereogenic Azepines via Pd(II)-Catalyzed Enantioselective C–H Olefination
The asymmetric construction of N-stereogenic compounds is a fundamental challenge in synthetic chemistry, primarily due to the low energy barrier for pyramidal inversion, leading to rapid racemization. While established strategies stabilize such centers through structural rigidification, efficient approaches to flexible N-chiral scaffolds remain scare. Herein, we report the highly enantioselective synthesis of a broad range of configurationally stable but flexible N-stereogenic tribenzo[b,d,f]azepines via palladium-catalyzed enantioselective C–H olefination (41 examples, up to >99% ee). The configurational stability originates from a distinctive saddle-shaped molecular conformation─a strategy different from conventional structural rigidification strategies that rely on covalently tethering all three N-substituents. The practicality of this protocol is demonstrated through gram-scale synthesis and downstream transformations to N-chiral carboxylic acid ligands. Moreover, these compounds exhibit good circularly polarized luminescence (CPL) with high dissymmetry factors (glum values up to 0.011), positioning them as promising candidates for advanced chiroptical materials.
Authors
- Pu‐Fan Qian (ORCID: https://orcid.org/0000-0003-2065-3669)
- Shu-song Wang
- Bing-Feng Shi
- Qi-Jun Yao
- Yuan Xu
- Yao-Le Jiang
- Bing-Jie Wang
Institutions
- Hangzhou Normal University (CN)
- State Key Laboratory of Pollution Control and Resource Reuse (CN)
- Henan Normal University (CN)
- Zhejiang University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- ACS Catalysis
- Published
- 2026-01-09
- DOI
- https://doi.org/10.1021/acscatal.5c08360
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00