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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Summary: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.
ISSN:2399-3669