Lei Fan, Jiwu Zhao, Huaming Sun, Weiqiang Zhang, Guofang Zhang, Yajun Jian, Ziwei Gao
The catalytic conversion of CO2 into arylacetic acids is of significant interest owing to the prevalence of these scaffolds in nonsteroidal anti-inflammatory drugs (NSAIDs) and fine chemicals. However, existing methods remain constrained by limited substrate scope, reliance on precious metals, or the need for stoichiometric additives. Herein, we report an earth-abundant titanium(iii)-catalyzed reductive carboxylation of benzyl halides with CO2 that operates via a radical-carbanion relay mechanism. This protocol accommodates primary, secondary, and tertiary C(sp3)-Cl bonds, benzyl bromides, and allylic chlorides, and proceeds without magnesium salt additives under oxygen-tolerant conditions. The synthetic utility is demonstrated by gram-scale reactions and the direct one-step synthesis of several NSAIDs. Mechanistic studies combining radical trapping, deuterium-labeling, intermediate characterization, and DFT calculations establish that Ti(iii) promotes inner-sphere chlorine-atom abstraction to generate a benzyl radical, which is captured, reduced to a benzyl anion, and subsequently trapped by CO2, thereby circumventing the prohibitive direct activation of CO2 at the metal center.