Visible-Light Photoredox-Catalyzed Direct Carboxylation of Tertiary C(sp³)–H Bonds with CO₂: Facile Synthesis of All-Carbon Quaternary Carboxylic Acids

Direct carboxylation of C-H bonds with CO₂ represents an attractive strategy to synthesize valuable carboxylic acids with high atom, step, and redox economy. Although great progress has been achieved in this field, catalytic carboxylation of tertiary C(sp³)-H bonds still remains challenging due to their inherent inertness and significant steric hindrance. Herein, we report a direct carboxylation of tertiary benzylic C(sp³)-H bonds with CO₂ via visible-light photoredox catalysis. Various all-carbon quaternary carboxylic acids, which are of significant importance in medicinal chemistry, are successfully obtained with high yields. This direct carboxylation is characterized by good functional group tolerance, broad substrate scope, and mild operational conditions. Furthermore, our methodology enables the efficient and rapid synthesis of key drug or bioactive molecules, such as carbetapentane, caramiphen, and PRE-084 (σ1 receptor agonist), and facilitates various functionalizations of C(sp²)-H bonds using the directing ability of target carboxylic acids, thus highlighting its practical applications. Mechanistic studies indicate that a carbanion, which serves as the key intermediate to react with CO₂, is catalytically generated via a single electron reduction of a benzylic radical through a consecutive photoinduced electron transfer process.