Nickel-Catalyzed LiCl-Controlled Switchable Carboxylation of Aryl C—F Bonds with One or Two Molecules of CO₂

Abstract

The use of CO₂ as a renewable C1 source for the synthesis of value-added chemicals can contribute to a more sustainable chemistry. In this work, a nickel-catalyzed amide-directed carboxylation of aryl C−F bonds with CO₂ has been developed. The reaction is switchable controlled by LiCl to react with one or two molecules of CO₂ to afford valuable phthalimides or α-hydroxycarboxylic acid derivatives. Further study shows that the reaction is a step-by-step process. The first step is a nickel-catalyzed carboxylation of aryl C−F bonds with CO₂ and tandem cyclization to afford phthalimides. The second step is a nickel-catalyzed C−N bond carboxylation of phthalimides with CO₂, and intramolecular nucleophilic addition of amide anion to the carbonyl. The carboxylation of phthalimides with CO₂ is also developed based on this reaction. The work features inert C−F bond functionalization, amide C−N bond activation, and multiple CO₂ incorporation. Mechanistic studies indicate that the azanickelacycle intermediates play an important role, and LiCl facilitates the reduction of Ni(II) to Ni(I) and promotes the carboxylation with the second molecule of CO₂. This protocol provides an efficient route for C−F bond functionalization under mild conditions via the chemical fixation of one or two molecules of CO₂.

Keywords

C−F Functionalization / Carbon Dioxide / Nickel / Carboxylation / C−N Bond Activation / Cross-coupling / Cyclization / C1 building blocks

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH