Consecutive hydrodefluorination for the regioselective synthesis of partially fluorinated arenes
- 1Division of Chemistry and Biological Chemistry, School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371
Abstract
Fluorinated arenes are critically important motifs in drug discovery, often exhibiting superior bioactivity compared to their non-fluorinated counterparts. While advances in fluorination methods have improved access to monofluoroarenes, the synthesis of di- and trifluoroarenes remains challenging. Here, we present a powerful method for access to partially fluorinated arenes via consecutive hydrodefluorination of perfluoroarenes, executed in one ‘pot’. This method utilises hydridosilicates as the reducing species, which are formed in situ by the combination of phenylsilane and cesium carbonate in dimethylsulfoxide. These conditions avoid precious metal catalysts and exotic reagents, exhibiting exceptional regioselectivity and control over the degree of defluorination. Through an in-depth mechanistic study, we found that hydridosilicates can perform hydrodefluorination by two distinct mechanisms, one thermal and one photochemical. These mechanisms are complementary in substrate scope—together, they enable a method with notable generality.
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BibTeX
@misc{tan2026consecutive,
title = {{Consecutive hydrodefluorination for the regioselective synthesis of partially fluorinated arenes}},
author = {Yanxian Tan and Howard Toh and Chieh-Yu Chang and Phillip S. Grant},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009852/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009852/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Consecutive hydrodefluorination for the regioselective synthesis of partially fluorinated arenes
AU - Yanxian Tan
AU - Howard Toh
AU - Chieh-Yu Chang
AU - Phillip S. Grant
PY - 2026
DA - 2026/10/05
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009852/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009852/v1
AB - Fluorinated arenes are critically important motifs in drug discovery, often exhibiting superior bioactivity compared to their non-fluorinated counterparts. While advances in fluorination methods have improved access to monofluoroarenes, the synthesis of di- and trifluoroarenes remains challenging. Here, we present a powerful method for access to partially fluorinated arenes via consecutive hydrodefluorination of perfluoroarenes, executed in one ‘pot’. This method utilises hydridosilicates as the reducing species, which are formed in situ by the combination of phenylsilane and cesium carbonate in dimethylsulfoxide. These conditions avoid precious metal catalysts and exotic reagents, exhibiting exceptional regioselectivity and control over the degree of defluorination. Through an in-depth mechanistic study, we found that hydridosilicates can perform hydrodefluorination by two distinct mechanisms, one thermal and one photochemical. These mechanisms are complementary in substrate scope—together, they enable a method with notable generality.
ER -