Redox-Neutral Carboxylation of Benzylic Tertiary C-H Bonds with Carbon Dioxide

Angew Chem Int Ed Engl. 2024 Nov 27:e202420852. doi: 10.1002/anie.202420852. Online ahead of print.

Abstract

The direct catalytic carboxylation of benzylic tertiary C-H bonds with CO2 for the synthesis of all-carbon quaternary carboxylic acids represents a significant challenge. Here, we present a redox-neutral approach to address this difficulty by leveraging the synergistic interplay between photocatalysis and cascade hydrogen abstraction cycles. Remarkably, this strategy eliminates the need for sacrificial electron donors, electron acceptors, or stoichiometric additives, offering enhanced atom economy and environmental sustainability. It is particular that the combination of α-amino alkyl radicals with sulfur radicals generated in situ from the decomposition of DMSO was employed to realize the abstraction of benzylic tertiary C-H bonds. Our method enables the direct synthesis of a diverse array of benzylic quaternary carboxylic acids with excellent functional group tolerance as well as the derivatization of bioactive molecules and the gram-scale synthesis of pharmaceuticals under mild reaction conditions.

Keywords: C-H bond; Photocatalysis; carbon dioxide; carboxylation; hydrogen atom transfer.