Direct synthesis of -perfluoro--butyl secondary amines from -trifluoromethyl secondary amines.

-Perfluoro--butyl (-PFB) secondary amines, harboring a unique F-reporting moiety linked directly to nitrogen, are highly attractive due to their diverse potential applications. However, their mild and facile synthesis remains a significant challenge. Herein, we present a safe and efficient strategy for the direct synthesis of -perfluoro--butyl secondary amines from readily available -trifluoromethyl secondary amines. Experiments and theoretical calculations demonstrate that this novel protocol encompasses three main processes: the elimination of hydrogen fluoride from the -trifluoromethyl precursor, consecutive addition-elimination conversion of difluoromethyl imine (R-N[double bond, length as m-dash]CF) to hexafluoropropyl imine (R-N[double bond, length as m-dash]C(CF)), and final addition of R-N[double bond, length as m-dash]C(CF) with the generated fluoroform (HCF). Key advantages of this reaction include the utilization of a single trifluoromethyl source and the -trifluoromethyl starting material itself as the hydrogen source. Notably, the elimination of hydrogen fluoride, facilitated by CsF, is critical for the success of this approach. This method is compatible with a broad range of functional groups, including heterocyclic compounds. F MRI experiments suggest promising prospects for PFB-labeled secondary amines as F MRI contrast agents.