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.
Chapman et al. (Tue,) studied this question.