Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indoles

Abstract Rearrangement reactions are generally considered to be a rapid and synergistic intramolecular reconstructing process that is insensitive to intermolecular intruders. We report that α-iminol rearrangements could be strategically redirected by the interception of Petasis reactions, in the con...

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Main Authors: Hui-Min Zhu, Tong Lei, Zhi-Xin Liao, Jia-Chen Xiang, An-Xin Wu
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-025-01528-9
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author Hui-Min Zhu
Tong Lei
Zhi-Xin Liao
Jia-Chen Xiang
An-Xin Wu
author_facet Hui-Min Zhu
Tong Lei
Zhi-Xin Liao
Jia-Chen Xiang
An-Xin Wu
author_sort Hui-Min Zhu
collection DOAJ
description Abstract Rearrangement reactions are generally considered to be a rapid and synergistic intramolecular reconstructing process that is insensitive to intermolecular intruders. We report that α-iminol rearrangements could be strategically redirected by the interception of Petasis reactions, in the context of being avoided by strong electron-withdrawing groups on the migrative aryl units. 1,4-Aryl migration prevails over 1,2-aryl migration via forming a boron-ate complex. By leveraging this reactivity, we developed a regiospecific synthesis of unsymmetrically 2,3-diaryl substituted indoles from three readily available feedstocks: an amine, an arylglyoxal, and a boronic acid. While traditional Petasis reactions with similar three-component inputs are typically applied to build C(sp3)-C(sp2) and C(sp3)-C(sp3) bonds, the present transformation offers a special opportunity for constructing a C(sp2)-C(sp2) linkage. Highly substituted indole motifs with structural diversity in the C2 position are easily accessed by this three-component reaction. A mechanism containing a copper-cobalt collaborative promotion process was suggested.
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spelling doaj-art-3da1bef0bbce4668a443aade03bfe7da2025-08-20T03:10:18ZengNature PortfolioCommunications Chemistry2399-36692025-05-018111010.1038/s42004-025-01528-9Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indolesHui-Min Zhu0Tong Lei1Zhi-Xin Liao2Jia-Chen Xiang3An-Xin Wu4School of Chemistry and Chemical Engineering, Southeast UniversitySchool of Chemistry and Chemical Engineering, Southeast UniversitySchool of Chemistry and Chemical Engineering, Southeast UniversitySchool of Chemistry and Chemical Engineering, Southeast UniversityState Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal UniversityAbstract Rearrangement reactions are generally considered to be a rapid and synergistic intramolecular reconstructing process that is insensitive to intermolecular intruders. We report that α-iminol rearrangements could be strategically redirected by the interception of Petasis reactions, in the context of being avoided by strong electron-withdrawing groups on the migrative aryl units. 1,4-Aryl migration prevails over 1,2-aryl migration via forming a boron-ate complex. By leveraging this reactivity, we developed a regiospecific synthesis of unsymmetrically 2,3-diaryl substituted indoles from three readily available feedstocks: an amine, an arylglyoxal, and a boronic acid. While traditional Petasis reactions with similar three-component inputs are typically applied to build C(sp3)-C(sp2) and C(sp3)-C(sp3) bonds, the present transformation offers a special opportunity for constructing a C(sp2)-C(sp2) linkage. Highly substituted indole motifs with structural diversity in the C2 position are easily accessed by this three-component reaction. A mechanism containing a copper-cobalt collaborative promotion process was suggested.https://doi.org/10.1038/s42004-025-01528-9
spellingShingle Hui-Min Zhu
Tong Lei
Zhi-Xin Liao
Jia-Chen Xiang
An-Xin Wu
Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indoles
Communications Chemistry
title Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indoles
title_full Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indoles
title_fullStr Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indoles
title_full_unstemmed Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indoles
title_short Intercepting an avoided α-iminol rearrangement with a Petasis reaction for the synthesis of 2,3-diaryl substituted indoles
title_sort intercepting an avoided α iminol rearrangement with a petasis reaction for the synthesis of 2 3 diaryl substituted indoles
url https://doi.org/10.1038/s42004-025-01528-9
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