A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides
Junliang Fu, Jun‐Yunzi Wu, Juan-Fen Shi, Long-Ling Huang, Honggen Wang, Qingjiang Li
Abstract
N-trifluoromethyl compounds, featuring a CF3 group directly attached to nitrogen, are valuable in medicinal chemistry. Despite substantial advances in their synthesis over the past decade, the efficient preparation of inherently unstable N-CF3 secondary amines remains a challenge in synthetic chemistry. Herein, we present a mild and practical method for synthesizing these compounds via oxidative fluorination of isocyanides using iodine as the oxidant, silver fluoride as the fluorinating reagent, and tert-butyldimethylsilane as the proton precursor. This approach benefits from simple workup, as all reagents and by-products can be easily removed through simple filtration and evaporation. This protocol features a broad substrate scope, good functional group tolerance, and good to excellent yields. Additionally, the resulting products can be readily converted into N-CF3 carbamoyl fluorides, valuable building blocks for the synthesis of diverse N-CF3 carbonyl derivatives. The efficient preparation of inherently unstable N-CF3 secondary amines remains a challenge in synthetic chemistry. Herein, the authors present the synthesis of this type of compounds via oxidative fluorination of isocyanides using iodine as the oxidant, silver fluoride as the fluorinating reagent, and tert-butyldimethylsilane as the proton precursor.