One-step synthesis of azepino[3,4-b]indoles by cooperative aza-[4 + 3] cycloaddition from readily available feedstocks

Azepino[3,4-b]indoles are a family of molecules with pharmaceutical significance that contain an aza-seven-membered ring system. However, synthetic approaches to this scaffold are limited and typically require multiple steps. Here, we demonstrate the feasibility of obtaining azepino[3,4-b]indoles by...

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Bibliographic Details
Published in:Organic chemistry frontiers an international journal of organic chemistry 2022-08, Vol.9 (17), p.4640-4648
Main Authors: Jin-Tian, Ma, Chen, Ting, Xiang-Long, Chen, Zhou, You, Zhi-Cheng, Yu, Shi-Yi, Zhuang, Alimu, Maierhaba, Yan-Dong, Wu, Jia-Chen, Xiang, An-Xin, Wu
Format: Article
Language:English
Subjects:
Amino acids
Aniline
Chemical synthesis
Cycloaddition
Indoles
Intermediates
Organic chemistry
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Summary:Azepino[3,4-b]indoles are a family of molecules with pharmaceutical significance that contain an aza-seven-membered ring system. However, synthetic approaches to this scaffold are limited and typically require multiple steps. Here, we demonstrate the feasibility of obtaining azepino[3,4-b]indoles by one-step synthesis from a four-component reaction system comprising readily available starting materials, i.e., an amino acid, an indole, and an aniline. This transformation affords a diverse range of azepino[3,4-b]indoles in a highly efficient manner. We propose that the self-sorting integration of two kinetically unstable intermediates, an indol-3-yl cation and an N-arylimine, is key to realizing the cooperative aza-[4 + 3] cycloaddition.
ISSN:2052-4110
2052-4110
DOI:10.1039/d2qo00816e