Electroreductive Defluorination Enables 1,1-Deuterocarboxylation of Difluoro- and Trifluoromethylarenes

Abstract

The defluorination-enabled functionalization not only provides an effective strategy to mitigate fluoride pollution, but also opens new avenues for constructing molecular diversity. Although numerous methods for C–F bond activation have been developed, their applications are typically confined to single defluorination-monofunctionalization processes. Traditional approaches to achieve 1,1-dual modification rely on multistep reaction sequences or precious-metal catalytic systems, which suffer from inefficiency, high cost, and significant environmental burden. In this study, we report the first electroreductive strategy for one-pot 1,1-deuterocarboxylation of C(sp³)–F bonds using cost-effective deuterium oxide (D₂O) as the deuterium source and carbon dioxide (CO₂) as a sustainable C1 feedstock. This method demonstrates broad substrate compatibility with difluoro-/trifluoroalkylarenes and enables late-stage drug functionalization without pre-activation. Mechanistic studies confirmed that the reaction proceeds via a sequential pathway: the substrate undergoes initial reduction at the cathode, reacts with CO₂, and then undergoes reduction by deuterium protonation in the presence of D₂O, ultimately leading to the formation of the final product.

Keywords

Electroreductive / Defluorination / 1,1-Deuterocarboxylation / Carboarylation / Deuteration / Tifluoromethylarenes / CO₂ / D₂O

RIGHTS & PERMISSIONS

2026 SIOC, CAS, Shanghai, & WILEY-VCH GmbH