Copper‐Mediated N‐Trifluoromethylation of O‐Benzoylhydroxylamines

Abstract

AbstractThe use of trifluoromethyl containing compounds is well established within medicinal chemistry, with a range of approved drugs containing C−CF3 and O−CF3 moieties. However, the utilisation of the N−CF3 functional group remains relatively unexplored. This may be attributed to the challenging synthesis of this unit, with many current methods employing harsh conditions or less accessible reagents. A robust methodology for the N‐trifluoromethylation of secondary amines has been developed, which employs an umpolung strategy in the form of a copper‐catalysed electrophilic amination. The method is operationally simple, uses mild, inexpensive reagents, and has been used to synthesise a range of novel, structurally complex N−CF3 containing compounds.