Formal group insertion into aryl C‒N bonds through an aromaticity destruction-reconstruction process

Nature Communications
Dandan HanRenhua Fan

Abstract

Given the abundance and the ready availability of anilines, the selective insertion of atoms into the aryl carbon-nitrogen bonds will be an appealing route for the synthesis of nitrogen-containing aromatic molecules. However, because aryl carbon-nitrogen bonds are particularly inert, anilines are normally activated by conversion to more reactive intermediates such as aryldiazonium salts to achieve functionalization of the aryl carbon-nitrogen bonds, but the nitrogen atom is usually not incorporated into products, instead being discarded. The selective insertion of groups into aryl carbon-nitrogen bonds remains an elusive challenge and an unmet need in reaction design. Here we show an aromaticity destruction-reconstruction process that selectively inserts a trimethylenemethane (TMM) group into the aromatic carbon-nitrogen bond of anilines concomitant with a benzylic carbon-hydrogen bond functionalization. This process provides a transformative mode for anilines, and the insertion products are versatile precursor to various nitrogen-containing aromatic molecules through simple conversions.

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Citations

Jan 30, 2020·Chemistry : a European Journal·Yuanhong MaJosep Cornella
Jul 17, 2020·The Journal of Organic Chemistry·Chideraa Iheanyi NwachukwuAndrew George Roberts

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Methods Mentioned

BETA
column chromatography

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