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Zhi Tu
Zhi Tu

Public Documents 1
Improved Direct 2-Trifluoromethylation of Quinoline Derivatives Using Me2(CH2Cl)SiCF3
Zhi Tu
Pei-Ying Peng

Zhi Tu

and 6 more

December 03, 2025
2-Trifluoromethylated aromatic azacycles such as quinoline and pyridine derivatives are interesting targets for the development of new drugs and agrochemicals. The direct C-H trifluoromethylation of aromatic azacycles using trimethyl(trifluoromethyl)silane (TMSCF 3) constitutes a facile approach for the C2-regioselective incorporation of a trifluoromethyl group into aromatic azacycles, but the yield and substrate scope wait for further improvement. Herein, we report an improved C2-regioselective trifluoromethylation of quinoline derivatives using Me 2(CH 2Cl)SiCF 3. Under a modified condition of Kanai & Kuninobu procedure involving sequential nucleophilic addition/oxidative aromatization process, an array of 2-CF 3 substituted quinoline derivatives (24 examples) could be obtained in good to excellent yields, obviously higher than those obtained by using TMSCF 3 (the yield increment of 10 examples was no less than 20%). Obviously enhanced yield is also observed in the 2-trifluoromethylation of naphthyridine and phenanthroline derivatives. These results imply that modifying the methyl group of TMSCF 3 by a suitable polar substituent may contribute to more powerful silyl trifluoromethylating reagents for the selective incorporation of a CF 3 group into aromatic azacycles.

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