Cu-Catalyzed Enantioselective and Divergent Synthesis of 5–5-Membered Atropisomers via Direct Atroposelective C–C/C–N Axial Bond Formation

Due to its inherently more distant ortho-groups, lower rotational energy barrier, and less stable configuration, the catalytic asymmetric synthesis of 5-5-membered atropisomers has remained underdeveloped, particularly through direct atroposelective C-N axial bond formation with no report to date. Moreover, developing a general strategy for the rapid and efficient construction of diverse 5-5-membered atropisomeric skeletons featuring either C-C or C-N axes continues to pose a formidable challenge. Herein, a Cu-catalyzed asymmetric carbene insertion of 3-diazoindolin-2-imines into readily available carbazoles and indoles is developed, leading to the atroposelective and divergent synthesis of axially chiral 5-5-membered bisindoles in generally good to excellent yield (up to 97% yield), enantioselectivity (up to 99% ee), and specific chemoselectivity. Notably, this work not only marks the first instance of preparing 5-5-membered C-N atropisomers via direct atroposelective C-N axial bond formation but also constitutes the first asymmetric C-H/N-H insertions via α-imino Cu-carbene. Remarkably, except for the original findings in 1971, X-ray photoelectron spectroscopy analyses were employed to identify Cu(I) as the active catalytic species within carbene reactions, which was also supported by theoretical calculations. Additionally, this protocol features great potential in organic luminescent materials, a broad substrate scope, and non-noble metal catalysis.

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Publication Details

Journal
Journal of the American Chemical Society
Published
2025-12-22
DOI
https://doi.org/10.1021/jacs.5c18193
Citations
1
Primary Topic
Axial and Atropisomeric Chirality Synthesis
Type
article
Field-Weighted Citation Impact
0.94
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article

Cu-Catalyzed Enantioselective and Divergent Synthesis of 5–5-Membered Atropisomers via Direct Atroposelective C–C/C–N Axial Bond Formation

Fucai Rao, Qian Peng-Cheng, Hao Tang, Long-Wu Ye et al.
1 citations
Journal of the American Chemical Society
Axial and Atropisomeric Chirality Synthesis
0.94
article

Cu-Catalyzed Enantioselective and Divergent Synthesis of 5–5-Membered Atropisomers via Direct Atroposelective C–C/C–N Axial Bond Formation

Fucai Rao, Qian Peng-Cheng, Hao Tang, Long-Wu Ye, Long Li, Yu-Wu Zhong, Wei-Lei Xiang, Shi-Jie Liu, Guan-Zhi Liu
article en
1 citations

Abstract

Due to its inherently more distant ortho-groups, lower rotational energy barrier, and less stable configuration, the catalytic asymmetric synthesis of 5-5-membered atropisomers has remained underdeveloped, particularly through direct atroposelective C-N axial bond formation with no report to date. Moreover, developing a general strategy for the rapid and efficient construction of diverse 5-5-membered atropisomeric skeletons featuring either C-C or C-N axes continues to pose a formidable challenge. Herein, a Cu-catalyzed asymmetric carbene insertion of 3-diazoindolin-2-imines into readily available carbazoles and indoles is developed, leading to the atroposelective and divergent synthesis of axially chiral 5-5-membered bisindoles in generally good to excellent yield (up to 97% yield), enantioselectivity (up to 99% ee), and specific chemoselectivity. Notably, this work not only marks the first instance of preparing 5-5-membered C-N atropisomers via direct atroposelective C-N axial bond formation but also constitutes the first asymmetric C-H/N-H insertions via α-imino Cu-carbene. Remarkably, except for the original findings in 1971, X-ray photoelectron spectroscopy analyses were employed to identify Cu(I) as the active catalytic species within carbene reactions, which was also supported by theoretical calculations. Additionally, this protocol features great potential in organic luminescent materials, a broad substrate scope, and non-noble metal catalysis.

Journal of the American Chemical SocietyVol. 148(1)
Wenzhou University (CN), Xiamen University (CN), Division of Materials Science and Engineering (AU), Fuzhou University (CN)
Affordable and clean energy
Openalex Percentile: Top 19%
Axial and Atropisomeric Chirality Synthesis
0.94
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