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General Access to <i>N</i>−CF<sub>3</sub> Secondary Amines and Their Transformation to <i>N</i>−CF<sub>3</sub> Sulfonamides

Leibing Wang, Jieping Wang, Sitao Ye, Beihan Jiang, Zihao Guo, Yasir Mumtaz, Wenbin Yi

2022Angewandte Chemie International Edition36 citationsDOI

Abstract

Abstract The synthesis of N −CF 3 compounds through fluorination or trifluoromethylation of N ‐containing compounds has been extensively investigated. However, general access to N −CF 3 compounds simply from N −CF 3 secondary amines is hampered by the challenging preparation and instability of these amines, as well as a much lower reactivity due to the strong electron‐withdrawing nature and steric bulk of the trifluoromethyl moiety. Herein, we report a general and highly efficient synthesis of N −CF 3 secondary amines with excellent isolated yields via the addition of the in situ generated difluoromethyl imine (R−N=CF 2 ) intermediates with hydrogen fluoride, which is mildly produced by triethylsilane and silver fluoride. N −CF 3 sulfonamides, highly desirable but scarce at present, are easily accessible from these valuable building blocks through an unprecedented route. This study will bring new vitality to the synthesis of N −CF 3 compounds.

Topics & Concepts

TrifluoromethylationChemistryTriethylsilaneTrifluoromethylMoietyFluorideReactivity (psychology)AnilineSteric effectsMedicinal chemistryCombinatorial chemistryStereochemistryOrganic chemistryCatalysisInorganic chemistryMedicineAlkylPathologyAlternative medicineFluorine in Organic ChemistryInorganic Fluorides and Related Compounds
General Access to <i>N</i>−CF<sub>3</sub> Secondary Amines and Their Transformation to <i>N</i>−CF<sub>3</sub> Sulfonamides | Litcius