B(C 6 F 5 ) 3 -Catalyzed Chemical Tagging of Bioactive N -Alkylamines through β-Amino C(sp 3 )–H Functionalization

We present a late-stage functionalization method for arming bioactive N-alkylamines with functional handles for bioconjugation through the transformations of β-amino C(sp3)-H bonds. B(C6F5)3 and a Brønsted base converts N-alkylamines into enamines through sequential hydride abstraction and deprotonation. The resulting enamines, generated in situ, undergo conjugate addition to maleimide-based tagging agents to furnish β-substituted amine derivatives bearing diverse bioconjugation handles. These transformations proceed under redox-neutral conditions and tolerate a range of Lewis acid-sensitive moieties.