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

利用 Petasis 反应拦截避免的 α-亚氨基醇重排,用于合成 2,3-二芳基取代的吲哚

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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(sp(3))-C(sp(2)) and C(sp(3))-C(sp(3)) bonds, the present transformation offers a special opportunity for constructing a C(sp(2))-C(sp(2)) 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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