Radical-carbanion relay enabled by earth-abundant titanium: carboxylation of 1°, 2°, and 3° benzyl chlorides with CO₂.

Authors

Lei Fan, Jiwu Zhao, Huaming Sun, Weiqiang Zhang, Guofang Zhang, Yajun Jian, Ziwei Gao

Published in

Chemical science. Aug 25, 2026. Epub Aug 25, 2026.

Abstract

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.

PMID:
42689201
Bibliographic data and abstract were imported from PubMed on 03 Sep 2026.

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