ABSTRACT We report herein the first copper‐mediated three‐component modular synthesis of N ‐fluoroalkyl amides from fluoroalkylcopper species (Cu I ─CF 3 , Cu I ─CF 2 CO 2 Et, and Cu I ─C 2 F 5 ), a nitrene precursor (dioxazolone), and an electrophile, featuring broad substrate scope and the unprecedented construction of acyclic N ‐C 2 F 5 and N ‐CF 2 CO 2 Et structures. The reaction proceeds via reaction of the dioxazolone with the fluoroalkylcopper complex to generate a nitrene/Cu intermediate, followed by nitrene migratory insertion into the Cu I ─C Rf bond as the pivotal step that directly forges the N– fluoroalkyl bond. Such a key step was supported by isolation and single‐crystal x‐ray characterization of intermediates ( L1 )Cu I N(CF 3 )(COAr) 5c and Cu I (N(CF 3 )(COAr)) 2 − 5d . Leveraging the versatile reactivity of copper, these intermediates react with various electrophiles to access a wide range of N ‐fluoroalkyl‐ N ‐alkyl(aryl)amides, and the derivatization of several drug molecules further demonstrates the synthetic utility of this approach.
Huang et al. (Mon,) studied this question.